Search

Simulation is a technique where the situation or a process is imitated. This process makes one to pretend the scenario. Aviation industry is one of the oldest industry which uses simulation technique to simulate the aviation technique. The main aim of having simulation lab is to make students acquire psychomotor skills before they actually treat the patients. Presently the National Medical Council of India has made it mandatory to have a skill lab but desirable to have a simulated mannequin for the training of medical students before actually treating the patients. Various advantages and disadvantages are appreciated in simulation technique. It is not very far that Dental council of India may make compulsory training of certain simulated modules in dentistry before treating the patient. Simulation lab in the pandemic like COVID has really helped people to undergo extensive training before treating patients, especially one who were catering the COVID ward or intensive care units. The simulation in dentistry is not a very old technique, certain technique are already in practice, but this article tries to highlight the necessity and gray areas where simulation can be improved for the benefit of students to learn and for the benefit of patients in view of safety.

The aim of the present study is to evaluate the clinical efficacy of Azadirachta Indica (A. Indica)/ neem mouth rinse in conjunction with scaling and root planning in the treatment of chronic gingivitis and chronic periodontitis. Total of 50 patients who were diagnosed with generalized chronic gingivitis and chronic periodontitis were divided equally into 2 groups. In first group subgingival ultrasonic instrumentation was performed along with the 0.2% chlorhexidine mouth rinse and in the other group 10% A. indica-mouth rinse was used. Clinical parameters were recorded on the baseline, 7thday, 30th day and 90th-day post-therapy. The intra-group comparison showed a statistically significant difference in clinical parameters at different intervals post-therapy whereas in the inter-group comparison the difference in clinical parameters was statistically non-significant at various time intervals. Neem mouthwash as an irrigant during ultrasonic scaling enhances the benefits of scaling and root planing in the treatment of chronic gingivitis and chronic periodontitis and can be used as an effective alternative for chlorhexidine.

The development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow–based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in patients with multiple myeloma. Complementary liquid biopsy–based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while others utilizing nucleic acid–based technologies are still developing and will prove important to further our understanding of the biology of MRD. On the regulatory front, multiple retrospective individual patient and clinical trial level meta-analyses have already shown and will continue to assess the potential of MRD as a surrogate for patient outcome. Given all this progress, it is not surprising that a number of clinicians are now considering using MRD to inform real-world clinical care of patients across the spectrum from smoldering myeloma to relapsed refractory multiple myeloma, with each disease setting presenting key challenges and questions that will need to be addressed through clinical trials. The pace of advances in targeted and immune therapies in multiple myeloma is unprecedented, and novel MRD-driven biomarker strategies are essential to accelerate innovative clinical trials leading to regulatory approval of novel treatments and continued improvement in patient outcomes.

Aims and Objectives: C-reactive protein is an acute-phase-reactant primarily produced by the liver in response to infection or trauma. Recent studies have demonstrated a correlation between periodontitis and elevated CRP levels. This study aims to relate the serum-CRP level in chronic and aggressive periodontitis patients, before and after periodontal treatment, with healthy controls. Materials and Method: A case-control clinical study was conducted with a total of 75 systemically healthy subjects, where 25 subjects were selected in each groups: Group I, Healthy control subjects; Group II, generalized chronic periodontitis patients, and Group III, generalized aggressive periodontitis patients. Serum-CRP levels were quantified by using turbidimetric immunoassay at baseline and 3month post-treatment. Kit used was “TURBILYTE-CRP” (Tulip Diagnostics, Goa, India). In the treatment phase, patients received single visit nonsurgical periodontal treatment, completed within 24hrs under LA for GCP & GAP group. Results: Mean serum CRP levels were significantly higher in both GCP and GAP groups as compared to the control group at baseline. On comparing the clinical parameters at 3 months post-treatment for GCP & GAP group with control group values, the mean score of serum CRP levels for the GAP group was statistically significant (P

Pemphigus vulgaris (PV) is a potentially life threatening and rare mucocutaneous disease that usually manifests first in the oral cavity and may later spread to the skin or other mucous membrane. Lesions may occur anywhere on the mucosa but it is unusual for PV to present over the gingiva as a primary site of involvement. A 64 year old female patient reported with a chief complaint of reddish, painful gums with burning sensation since 8 years. The diagnosis of PV is based on clinical findings (Nikolsky’s sign positive) and confirmed by histopathological analysis. Medications were prescribed as per indications and requirements. Oral hygiene instructions were given. No recurrence was observed at 1½ year of follow-up. Thus, this case serves to enhance our awareness of gingiva as a site at which systemic disease can manifests itself.

Background: Frenum that encroaches on the margin of the gingiva may interfere with plaque removal and can lead to gingival recession and midline diastema. Thus, to maintain proper oral hygiene and prevent gingival recession, frenectomy is done. Frenectomy can be accomplished by conventional frenectomy technique, which has certain disadvantages. To overcome those drawbacks, paralleling technique of frenectomy has been introduced. Both the techniques can be performed by using various treatment modalities. Aim: The purpose of this clinical study was to compare the bleeding during surgery, post-operative wound healing and patient's perception towards the conventional frenectomy technique with scalpel, paralleling frenectomy technique with scalpel and paralleling technique with electrocautery. Materials and method: A total of 30 subjects with gingival or papillary frenal attachment were selected and equally divided into three groups. Group 1 was treated by conventional technique with scalpel, Group 2 by paralleling technique with scalpel and Group 3 by paralleling technique with electrocautery. Various parameters such as bleeding during surgery, patient's perception towards the various techniques and post-operative wound healing were evaluated. Results: The results showed that bleeding during surgery was minimum in group 3 as compared to other two groups. Patient's perception towards paralleling technique with scalpel, was found better than the other groups. At 7th day, though there was a difference in the healing but at 21st day wound healing was almost similar in all the three groups. Conclusion: Based on our findings and clinical outcome, paralleling technique with scalpel provided better patient's perception and an efficient and satisfactory option for frenectomy.

Next generation sequencing studies in Chronic lymphocytic leukemia (CLL) have revealed novel genetic variants that have been associated with disease characteristics and outcome. The aim of this study was to evaluate the prognostic value of recurrent molecular abnormalities in patients with CLL. Therefore, we assessed their incidences and associations with other clinical and genetic markers in the prospective multicenter COMPLEMENT1 trial (treatment naive patients not eligible for intensive treatment randomized to chlorambucil (CHL) vs. ofatumumab-CHL (O-CHL)). Baseline samples were available from 383 patients (85.6%) representative of the total trial cohort. Mutations were analyzed by amplicon-based targeted next generation sequencing (tNGS). In 52.2% of patients we found at least one mutation and the incidence was highest in NOTCH1 (17.0%), followed by SF3B1 (14.1%), ATM (11.7%), TP53 (10.2%), POT1 (7.0%), RPS15 (4.4%), FBXW7 (3.4%), MYD88 (2.6%) and BIRC3 (2.3%). While most mutations lacked prognostic significance, TP53 (HR2.02,p

Belantamab mafodotin (belamaf) is a BCMA-targeted antibody–drug conjugate recently approved as monotherapy for adults with relapsed/refractory multiple myeloma who have received ≥4 prior therapies. Belamaf binds to BCMA and eliminates myeloma cells by multimodal mechanisms of action. The cytotoxic and potential immunomodulatory properties of belamaf have led to novel combination studies with other anticancer therapies. Here, we describe the rationale and design of DREAMM-5, an ongoing Phase I/II platform study evaluating the safety and efficacy of belamaf combined with novel agents, including GSK3174998 (OX40 agonist), feladilimab (an ICOS; GSK3359609), nirogacestat (a gamma-secretase inhibitor; PF-03084014) and dostarlimab (a PD-1 blocker) versus belamaf monotherapy for patients with relapsed/refractory multiple myeloma.Clinical trial registration: NCT04126200 (ClinicalTrials.gov).

Hemangioma is a relatively common benign proliferation of blood vessels that primarily develops during childhood. Two main forms of hemangioma recognized: capillary and cavernous. The capillary form presents as a flat area consisting of numerous small capillaries. Cavernous hemangioma appears as an elevated lesion of a deep red color, and consists of large dilated sinuses filled with blood. The present case report is an presentation of gingival growth, which was clinically diagnosed as gingival polyp but histopathologically as capillary haemangioma. These lesions present as a diagnostic dilemma to the clinician and can lead to serious complications if not carefully managed. The purpose of the case report is to present the case of a capillary hemangioma in a patient and to describe the successful treatment of this case.

8019 Background: Preclinical data demonstrate that nirogacestat, a gamma-secretase inhibitor, may increase cell-surface levels of a B-cell maturation antigen (BCMA) and reduce soluble BCMA levels, which could enhance anti-BCMA agent activity in multiple myeloma. In the DREAMM-5 (NCT04126200) Phase I/II platform trial belantamab mafodotin (belamaf; BLENREP), a BCMA-targeting antibody-drug conjugate, is being evaluated in combination with nirogacestat to determine if the combination can result in similar efficacy and an improved ocular safety profile compared to the currently approved belamaf schedule (single agent dose 2.5 mg/kg Q3W) in patients with RRMM which showed a 31% overall response rate (ORR) and 44.5% Gr3/4 keratopathy (BLENREP US prescribing information). Methods: This cohort within the DREAMM-5 nirogacestat combination sub-study has a sequential dose-exploration (DE) phase evaluating 0.95 mg/kg Q3W belamaf with 100 mg BID nirogacestat continuously, followed by a randomized cohort expansion (CE) comparing the combination to a belamaf 2.5 mg/kg Q3W arm. Results: Preliminary results from the 10 patients (pts) in the DE cohort with low-dose belamaf + nirogacestat are presented in this abstract. Pts had a median (range) of 4.5 (3–10) prior lines of therapy. At time of data cut-off (Nov 15, 2021), pts received a median (range) of 7 cycles (1–26). The ORR was 60% (n=6/10) and 20% (n=2) achieved a very good partial response (Table). The key emergent adverse events (AEs) included ocular events (n=7 [70%]; ≥Grade [Gr] 3, n=2 [20%] of which Gr 3 keratopathy was reported in 1 pt [10%]), diarrhea (n=7 [70%]; Gr 3, n=1 [10%]) and hypophosphatemia (n=7 [70%]; Gr 3, n=1, [10%]). There were 2 Grade 5 AEs, neither of which were related to study treatment. No pt permanently discontinued study due to treatment related AEs. Conclusions: Encouraging clinical activity and a manageable safety profile is observed with low dose belamaf (0.95 mg/kg Q3W) + nirogacestat (100 mg BID continuously) in pts with RRMM. This ongoing sub-study is actively recruiting patients and will continue to evaluate belamaf + nirogacestat efficacy and safety. Updated results will be reported at the congress. Funding: GSK (208887); drug linker technology licensed from Seagen Inc.; mAb produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT04126200. [Table: see text]

Introduction Patients with relapsed or refractory multiple myeloma (RRMM) represent an unmet clinical need. Belantamab mafodotin (belamaf; GSK2857916) is a first-in-class antibody–drug conjugate (ADC; or immunoconjugate) that delivers a cytotoxic payload, monomethyl auristatin F (MMAF), to myeloma cells. In the phase II DREAMM-2 study (NCT03525678), single-agent belamaf (2.5 mg/kg) demonstrated clinically meaningful anti-myeloma activity (overall response rate 32%) in patients with heavily pretreated disease. Microcyst-like epithelial changes (MECs) were common, consistent with reports from other MMAF-containing ADCs. Methods Corneal examination findings from patients in DREAMM-2 were reviewed, and the clinical descriptions and accompanying images (slit lamp microscopy and in vivo confocal microscopy [IVCM]) of representative events were selected. A literature review on corneal events reported with other ADCs was performed. Results In most patients receiving single-agent belamaf (72%; 68/95), MECs were observed by slit lamp microscopy early in treatment (69% had their first event by dose 4). However, IVCM revealed hyperreflective material. Blurred vision (25%) and dry eye (15%) were commonly reported symptoms. Management of MECs included dose delays (47%)/reductions (25%), with few patients discontinuing due to MECs (1%). The first event resolved in most patients (grade ≥2 MECs and visual acuity [each 77%], blurred vision [67%], and dry eye [86%]), with no reports of permanent vision loss to date. A literature review confirmed that similar MECs were reported with other ADCs; however, event management strategies varied. The pathophysiology of MECs is unclear, though the ADC cytotoxic payload may contribute to on- or off-target effects on corneal epithelial cells. Conclusion Single-agent belamaf represents a new treatment option for patients with RRMM. As with other ADCs, MECs were observed and additional research is warranted to determine their pathophysiology. A multidisciplinary approach, involving close collaboration between eye care professionals and hematologist/oncologists, is needed to determine appropriate diagnosis and management of these patients. Trial Registration ClinicalTrials.gov Identifier, NCT03525678.

Introduction: The bortezomib, lenalidomide, and dexamethasone (VRd) regimen is an acceptable standard of care (SoC) for both transplant-eligible and transplant-ineligible newly diagnosed multiple myeloma (TI NDMM). Ongoing development of novel therapies and combinations strive to improve survival outcomes beyond what is expected from SoC. Belantamab mafodotin (belamaf) is a B-cell maturation antigen-binding antibody-drug conjugate that eliminates myeloma cells by a multimodal mechanism and has demonstrated durable responses in patients with relapsed/refractory multiple myeloma (RRMM). Preclinical evidence of belamaf in combination with bortezomib or lenalidomide suggests enhanced anti-myeloma activity, providing rationale for this treatment combination. We report the preliminary findings of belamaf + VRd for TI NDMM patients. Methods: DREAMM-9 (NCT04091126) is an ongoing Phase I, open-label, randomized, dose and schedule evaluation study of belamaf + VRd in patients with TI NDMM. Eligible patients include those ≥18 years old with ECOG status 0-2 and adequate organ system functions. The study evaluates safety and tolerability of belamaf + VRd in up to 8 cohorts, up to 144 patients, to establish the recommended phase 3 dose (RP3D). VRd is administered Q3W until cycle 8, followed by lenalidomide + dexamethasone (Rd) Q4W. Belamaf + VRd is administered until cycle 8, and then in combination with Rd thereafter. The belamaf dose cohorts currently being evaluated are: cohort 1 (1.9 mg/kg Q3/4W), cohort 2 (1.4 mg/kg Q6/8W), cohort 3 (1.9 mg/kg Q6/8W), cohort 4 (1.0 mg/kg Q3/4W), and cohort 5 (1.4 mg/kg Q3/4W). After evaluation of safety data for cohort 1, cohorts 2-5 were opened in parallel and enrolled patients were randomized 1:1:1:1. Safety data, clinical activity, and drug concentrations will be assessed, and used to determine the belamaf RP3D. This analysis reports the preliminary results from cohort 1. Primary endpoints include number of patients with adverse events (AEs). Secondary endpoints include establishing relative dose intensity of lenalidomide and bortezomib in combination with belamaf, cumulative dose of belamaf, pharmacokinetics (PK) profile of belamaf when combined with VRd, overall response rate (ORR), complete response (CR), stringent complete response (sCR), complete response rate ([CRR]; % of patients with a confirmed CR or better), and rate of very good partial response or better (≥VGPR). Exploratory endpoints include assessing minimal residual disease (MRD) in patients who achieve ≥VGPR, and safety and efficacy exposure-response relationships. Results: Twelve patients in cohort 1 were included in this preliminary analysis. Eight patients (67%) were male; median age (range) was 72.5 years (63-77). Ten patients (83%) were white and 2 (17%) were Asian. Nine patients (75%), were ISS stage II or III, and 4 (33%) patients had high-risk cytogenetics (consisting of one or more of the following: t(4;14), t(14;16), del17p, 17p13del). AEs related to study treatment were experienced by all 12 patients. Dose reductions occurred in 12 (100%) patients, all of whom also experienced a dose delay. Most common AEs leading to dose modification were thrombocytopenia, neutropenia, and corneal events. Grade 3 or 4 AEs related to belamaf occurred in 9 (75%) patients. During the trial, one patient experienced a fatal severe AE due to COVID-19 infection (unrelated to study treatment; Table). All patients, 100% (n=12; 95% CI: 73.5-100) achieved ≥VGPR. Early deep responses were observed; 2 (17%) patients achieved VGPR as early as 4 weeks. As of data cut-off, 5 (42%) remain in CR and 3 (25%) in sCR. Based on real-time data captured in the clinical database, 7 out of 9 patients achieved MRD-negative status at the first test after VGPR. Belamaf PK profile was similar to that observed in patients with RRMM taking into consideration baseline patients characteristics. Conclusion: Preliminary data suggest addition of belamaf to VRd did not reveal new safety signals and demonstrates high response rates, albeit with short follow-up. The study is ongoing to confirm safety and evaluate the efficacy of belamaf + VRd. Updated data for cohort 1 will be reported at the congress. Funding: GSK (Study 209664); belamaf drug linker technology licensed from Seagen; belamaf monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Figure 1 Figure 1. Disclosures Usmani: Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Takeda: Consultancy, Research Funding, Speakers Bureau; Merck: Consultancy, Research Funding; SkylineDX: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Janssen Oncology: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; EdoPharma: Consultancy; GSK: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; Array BioPharma: Consultancy, Research Funding; Abbvie: Consultancy; Amgen: Consultancy, Research Funding, Speakers Bureau. Quach: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees. Koh: Pfizer: Consultancy; Jassen: Honoraria; AstraZeneca: Honoraria; Novartis: Honoraria; GSK: Honoraria; Roche: Honoraria; Takeda: Honoraria. Guenther: Novartis: Consultancy; Celgene: Consultancy, Honoraria; Roche: Consultancy; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AbbVie: Consultancy; Jazz Pharmaceuticals: Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria. Zhou: GlaxoSmithKline: Current Employment. Kaisermann: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Mis: GlaxoSmithKline: Current Employment. Williams: GlaxoSmithKline: Current Employment. Yeakey: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Ferron-Brady: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Figueroa: GlaxoSmithKline: Current Employment. Kremer: GlaxoSmithKline: Current Employment. Gupta: Novartis: Current equity holder in publicly-traded company; GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Janowski: Celgene: Consultancy; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees.

Background Single-agent belamaf, a B-cell maturation antigen-targeting antibody-drug conjugate, induced durable responses with a manageable safety profile in patients with RRMM at 13 months of follow-up (DREAMM-2; NCT03525678). The unique multimodal mechanisms of action (MoAs) of belamaf, in combination with MoAs of selected agents, have the potential to achieve synergistic effects in RRMM to further enhance the benefit-risk profile. Belamaf is being evaluated in DREAMM-5 in various lines of treatment, as monotherapy or in combination with other agents. Methods DREAMM-5 (NCT04126200) is a phase 1/2 platform study that utilizes a master protocol with separate sub-studies comprised of sequential dose-exploration (DE) and cohort-expansion (CE) phases to identify effective belamaf combinations compared with a shared single-agent belamaf control arm (CE phase only). In the DE phase, patients will be assigned to one of the multiple belamaf dosing combination cohorts by a predetermined algorithm (N≤10 per cohort). A recommended phase 2 dose (RP2D) for each combination will be identified based on safety and preliminary efficacy in the DE phase. An interim analysis of safety, pharmacokinetic, biomarker, and efficacy data will be performed for each combination to determine if it should move forward to the CE phase. Patients in the CE phase (N≥35 per cohort) will be randomized to a sub-study, and within a sub-study, to either the combination arm or belamaf control arm. Patients will also be stratified by number of prior therapies; eligible patients will have received ≥3 prior lines, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody. All patients will provide informed consent for participation. Primary objectives of the study are to identify the RP2D (DE phase), the overall response rate (≥partial response, CE phase), and safety and tolerability for each combination. Sub-study 1 (combination with GSK3174998, OX40 agonist antibody) is no longer open to enrollment. Sub-studies 2 (combination with GSK3359609, feladilimab, anti-ICOS agonist), 3 (combination with nirogacestat [PF-03084014; SpringWorks Therapeutics], gamma-secretase inhibitor), and 4 (combination with dostarlimab, PD-1 antagonist antibody) are currently open to enrollment. Sub-study 5 (combination with isatuximab [Sanofi], CD38 antagonist antibody) will be open to enrollment soon. Additional sub-studies will be explored based on scientific rationale and/or available preclinical combination data. Funding GSK (208887; NCT04126200). Belamaf drug linker technology licensed from Seagen Inc.; mAb produced using POTELLIGENT Technology licensed from BioWa. Nirogacestat and isatuximab produced by and used in collaboration with SpringWorks Therapeutics and Sanofi, respectively Encore Statement ©2021 European Hematology Association, Inc. Reused with permission. This abstract was accepted and previously presented at the 2021 EHA Annual Meeting. All rights reserved.

Context Belamaf is a B-cell maturation antigen-targeting antibody-drug conjugate approved in the US and EU for the treatment of RRMM. Ocular events (OEs) during the DREAMM-2 trial (NCT03525678) included corneal exam findings (punctate keratopathy and microcyst-like epithelial changes), BCVA changes, and ocular symptoms. Dose reductions or delays based on corneal exam findings and BCVA were used to manage OEs. Objective To study relationships between exam findings, BCVA changes, and patient-reported ocular symptoms in a post hoc analysis to explore if BCVA changes and symptoms alone could guide dosing. Methods Patients receiving single-agent belamaf (2.5 mg/kg) had eye evaluations (including a corneal exam and BCVA assessment of Snellen visual acuity) performed by ophthalmologists at baseline and prior to each dose. Changes in the corneal epithelium (Ker) and BCVA were assessed per protocol-defined criteria and assessment of grade was based on the worse eye. BCVA grading was relative to baseline. Patient-reported ocular symptoms were reported per the Common Terminology Criteria for Adverse Events. Results In 12.5% of eye evaluations Grade 3–4 Ker was associated with minimal or no (Grade ≤1) BCVA changes. When patient-reported ocular symptoms were also considered, only 7.5% of evaluations found Grade 3–4 Ker with Grade ≤1 BCVA changes or ocular symptoms. Mild or no (Grade ≤2) Ker was associated with Grade ≤1 BCVA changes in 59.5% of evaluations, or in 38.8% of evaluations with no ocular symptoms reported. Overall, Grade 3–4 Ker were found in 24.9% of evaluations; by contrast, patients had Grade 2–4 BCVA changes or ocular symptoms in 53.7% of evaluations. Conclusions BCVA changes and ocular symptoms should be further investigated to determine if they can be used as alternatives (e.g., frequency of eye examinations based on symptoms) for the management of belamaf dosing to potentially reduce the burden on patients and healthcare professionals. Funding GlaxoSmithKline (205678; NCT03525678). Drug linker technology licensed from Seagen Inc.; mAb produced using POTELLIGENT Technology licensed from BioWa. © 2021 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2021 ASCO Annual Meeting. All rights reserved.

Introduction: Belantamab mafodotin (belamaf; GSK2857916) is a B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate. In the pivotal Phase II DREAMM-2 study, single-agent belamaf demonstrated deep and durable responses and a manageable safety profile in patients refractory and/or intolerant to ≥3 lines of therapy, including an anti-CD38 monoclonal antibody such as daratumumab (Lonial et al. Lancet Oncol 2020). Responses were sustained at 13 months of follow-up with belamaf (2.5 mg/kg intravenously [IV] every 3 weeks [Q3W]); overall response rate (ORR) was 32% and median duration of response (DoR) was 11.0 months (Lonial et al. ASCO 2020 Poster 436). Triple combination regimens, such as daratumumab plus bortezomib and dexamethasone (D-Vd), are considered a standard of care for patients with RRMM and have demonstrated superior antimyeloma activity to monotherapy and dual combination regimens, such as bortezomib and dexamethasone. Preclinical data suggest synergistic antimyeloma activity of belamaf and bortezomib (a proteasome inhibitor), and initial results from the ongoing Phase I/II DREAMM-6 study of B-Vd indicate an acceptable safety profile for the combination (Nooka et al. ASCO 2020 Oral 8502). The DREAMM-7 study (NCT04246047) will evaluate the efficacy and safety of B-Vd compared with D-Vd in patients with RRMM. Methods: DREAMM-7 is an ongoing, randomized, open-label, global, multicenter, Phase III, two-arm study in patients with measurable RRMM who had received ≥1 prior therapy with documented disease progression during or after their most recent therapy. Patients aged ≥18 years with Eastern Cooperative Oncology Group Performance Status 0-2, adequate organ system function, and who provide informed consent will be eligible. Patients intolerant/refractory to daratumumab or bortezomib, or with prior exposure to anti-BCMA therapy, will be excluded. Patients will be stratified by the Revised International Staging System, prior exposure to bortezomib, and number of prior lines of therapy. Approximately 478 patients will be randomized (1:1) to Arm A (B-Vd) or Arm B (D-Vd). In Arm A, patients will receive belamaf 2.5 mg/kg (IV) Q3W on Day 1 of each cycle; bortezomib 1.3 mg/m2 (subcutaneously) on Days 1, 4, 8, and 11 of Cycles 1-8 (21-day cycles); and dexamethasone 20 mg (IV or orally) on the day of, and the day after, bortezomib treatment. In Arm B, patients will receive daratumumab 16 mg/kg (IV) in 21-day cycles: Cycles 1-3 Q1W, Cycles 4-8 Q3W, and from Cycle 9 onwards Q4W; dexamethasone and bortezomib schedules will be the same as in Arm A. Treatment will continue in both arms until disease progression, death, unacceptable toxicity, withdrawal of consent, or study end. The primary endpoint is progression-free survival (PFS; time from randomization to the earliest date of documented disease progression or death [any cause]). The key secondary endpoint is minimal residual disease negativity rate, as assessed by next-generation sequencing. Additional secondary endpoints include complete response rate, ORR, DoR, PFS2 (PFS after initiation of new anticancer therapy), overall survival, and endpoints related to pharmacokinetics, antidrug antibodies, safety, and health-related quality of life. As of August 2020, the study is enrolling. Funding: GSK (Study 207503); drug linker technology licensed from Seattle Genetics; mAb produced using POTELLIGENT Technology licensed from BioWa. Disclosures Rifkin: McKesson: Current equity holder in publicly-traded company, Ended employment in the past 24 months, Other: Stock ownership; Takeda, Amgen, Celgene, BMS, Mylan, Coherus BioSciences, Fresenius: Consultancy; AbbVie: Other: Investigator in AbbVie sponsored clinical trials; Takeda, Amgen, BMS (Celgene): Membership on an entity's Board of Directors or advisory committees. Boyd:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Di Raimondo:Amgen: Consultancy, Honoraria; GILEAD, Incyte: Research Funding; Amgen, Takeda, Novartis: Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Dimopoulos:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees. Weisel:Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Adaptive: Consultancy, Honoraria; GlaxoSmithKline: Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Arnulf:BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria. Hajek:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Pharma MAR: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Spencer:AbbVie, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Consultancy; Amgen, Celgene, Haemalogix, Janssen, Servier and Takeda: Research Funding; AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Honoraria; Celgene, Janssen and Takeda: Speakers Bureau. Davis:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Riccio:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Kim:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Wilkes:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Rutledge:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Talekar:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Kremer:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Gupta:Novartis: Current equity holder in publicly-traded company; GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Mateos:Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; PharmaMar-Zeltia: Consultancy; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria; GlaxoSmithKline: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Introduction: The treatment paradigm for RRMM is characterized by continuous treatment to suppress the malignant plasma cell clone. Some treatments may affect the eye, leading to a broad spectrum of ocular disorders, from dry eye to glaucoma, causing impaired quality of life. Therefore, we examined the baseline eye health of patients with RRMM receiving single-agent belamaf in the DREAMM-2 study (NCT03525678) and compared the findings to those of age-matched individuals in the general population. A better understanding of baseline ocular status is important as patients may have existing, undiagnosed eye conditions that may affect future treatment options. Methods: DREAMM-2 investigated belamaf, a B-cell maturation antigen-targeted antibody-drug conjugate in patients with RRMM. Eligible patients had received ≥3 prior therapies and were refractory to an immunomodulatory agent, a proteasome inhibitor, and refractory and/or intolerant to an anti-CD38 monoclonal antibody. Prior to receiving belamaf, patients underwent systematic ocular history collection and eye examination and completed the eye-specific National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25). We report pretreatment eye-related findings to describe the baseline ocular status of patients with RRMM in DREAMM-2. Results: Of 221 patients enrolled, 100 (45%) were female and 121 (55%) were male, with a median age (range) of 66 years (34-89), median time from diagnosis of 5.4 years (1.1-12.1), and median 6 (3-21) prior lines of therapy; 98% patients had received bortezomib. Previous ocular history reported by patients were cataract (60%), intraocular surgery and/or laser treatment (35%), dry eye (20%), and glaucoma (6%), and history of ocular disease requiring medical treatment (12%). On examination, the mean best corrected visual acuity (BCVA) Snellen score was worse than 20/50 in one or both eyes in 20 and 4 of 218 patients with data, respectively. Blepharitis (anterior) was evident in approximately 20% and the corneal epithelium was abnormal (mainly mild-grade keratopathy) in 43% of patients. Impaired tear film production was reported with meibomian gland dysfunction (MGD) in 33% of patients, and evidence of dry eye (Schirmer's test, median 8.2 mm [normal ≥15 mm] in the worse eye. Median worse-eye tear break up time was 8.6 sec [normal >10 sec]). Slit-lamp examination revealed a cataract in approximately 50% of patients. Ten (8%) patients had evidence of prior cataract surgery with an implanted lens (pseudophakia). Dilated fundoscopy identified an abnormal optic nerve in 10% of patients in either eye; of these, glaucomatous cupping was noted in 43% (right eye) to 50% (left eye) of patients. Median (range) overall composite vision score by NEI-VFQ-25 was 95.3 (28-100). Conclusions: There was a 60% prevalence of cataract in the study cohort and an increased prevalence of glaucoma (6% vs expected 3% in patients >65 years old; Kreft et.al. BMC Public Health 2019) in RRMM patients treated in the DREAMM-2 study. Both conditions can be associated with corticosteroids, often used in MM treatments, although cataract is also an age-related phenomenon. We noted a significant number of patients with blepharitis (anterior), dry eye, and MGD, which may be associated with prior bortezomib treatment. Forty-three percent of patients had an abnormal corneal epithelium at baseline, which may be related to dry eye. This is relevant as belamaf is associated with keratopathy (microcyst-like epithelial changes visible on slit-lamp examination, with or without symptoms). Overall NEI-VFQ-25 scores were comparable to those reported in patients >65 years old (Nickels et al. Health Qual Life Outcomes 2017). Patients with RRMM may have a number of baseline ocular abnormalities suggesting a need for regular ophthalmic examinations in this vulnerable population to identify and manage underlying conditions and treatment-related complications. Specifically, attention should be paid to patients who may have ocular conditions associated with prior treatment with corticosteroids or bortezomib. The optimization of ocular heath in this population is particularly relevant given that emerging RRMM therapies such as belamaf are associated with significant ocular side effects. Funding: GSK (Study 205678); drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Disclosures Popat: GSK: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Celgene: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); AbbVie: Consultancy, Honoraria. Farooq:University of Chicago: Current Employment; GlaxoSmithKline: Consultancy. Thulasi:Emory University: Current Employment. Lonial:Novartis: Consultancy, Honoraria, Other: Personal fees; Janssen: Consultancy, Honoraria, Other: Personal fees, Research Funding; BMS: Consultancy, Honoraria, Other: Personal fees, Research Funding; GSK: Consultancy, Honoraria, Other: Personal fees; Abbvie: Consultancy; Merck: Consultancy, Honoraria, Other: Personal fees; Takeda: Consultancy, Other: Personal fees, Research Funding; Amgen: Consultancy, Honoraria, Other: Personal fees; Sanofi: Consultancy; Genentech: Consultancy; Karyopharm: Consultancy; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; JUNO Therapeutics: Consultancy; Millennium: Consultancy, Honoraria; Onyx: Honoraria. Jakubowiak:AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive, Juno: Consultancy, Honoraria. Badros:Amgen: Consultancy; University of Maryland: Current Employment. Jeng:University of Maryland: Current Employment; EyeGate: Current equity holder in publicly-traded company; Kedrion, Merck, GSK: Consultancy. Opalinska:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Baron:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Piontek:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Byrne:Adaptimmune, Novartis: Current equity holder in publicly-traded company; GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Womersley:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Gupta:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company. Degli Esposti:Moorfields Eye Hospital: Current Employment; GlaxoSmithKline: Consultancy, Honoraria.

Introduction: IRRs are commonly reported by patients receiving intravenous (IV) treatments for RRMM (Nooka et al. J Oncol Pract 2018); these can be troublesome for patients and can lead to discontinuation of treatment, negatively impacting durability of response. In the Phase II DREAMM-2 study (NCT03525678), single-agent belamaf (GSK2857916), a first-in-class B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate, demonstrated deep and durable responses with a manageable safety profile in patients with heavily pre-treated RRMM (Lonial et al. ASCO 2020; poster 436). As expected with IV biologic agents, IRRs were commonly reported in this study, but were considered self-limited. Here, we report details on IRRs for patients receiving belamaf 2.5 mg/kg (the recommended dose for future clinical development) after 13-months of follow-up. Methods: In the DREAMM-2 study, patients with RRMM progressing after ≥3 prior therapies, refractory to an immunomodulatory agent and a proteasome inhibitor, and refractory and/or intolerant to an anti-CD38 monoclonal antibody, and who provided informed consent, received single-agent belamaf (2.5 or 3.4 mg/kg IV every 3 weeks) on Day 1 of each cycle until disease progression or unacceptable toxicity. Pre-medication for IRR prophylaxis was not protocol mandated (administered per investigator discretion, if deemed medically appropriate). These events were graded by Common Terminology Criteria for Adverse Events criteria version 4.03 and included the terms: IRR, pyrexia, chills, diarrhea, nausea, asthenia, hypertension, hypotension, lethargy, and tachycardia. Grade 2 IRRs were managed by stopping the infusion, providing medical treatment and continuing the infusion at half the original infusion rate until resolution to Grade ≤1. Grade 3 IRRs were managed by discontinuing the infusion until recovery to Grade ≤1, after which the treatment could only continue (with pre-medication and a longer infusion time) following discussion with the study sponsor; all future infusions were pre-medicated. Patients experiencing Grade 4 IRRs were permanently withdrawn from the study. IRRs were followed until resolution/stabilization. Results: After 13-months of follow-up, IRRs occurred in 20/95 (21%) patients; most were mild to moderate in severity, with no Grade 4 or 5 events (Grade 1, n=6 [30%]; Grade 2, n=11 [55%]; Grade 3, n=3 [15%]). Pyrexia was reported in 5/20 (25%) patients; chills, diarrhea, and nausea in 2/20 (10%) each; asthenia, hypertension, lethargy, and tachycardia in 1/20 (5%) patients each; and the adverse event term 'IRR' was recorded for 16/20 (80%) patients. In most patients (18/20 [90%]), IRRs occurred during Cycle 1, and the incidence of these events declined thereafter (Figure). Of 73/95 (77%) patients without pre-medication at Cycle 1, 12 (16%) experienced an IRR. A total of 22/95 (23%) patients received a pre-medication at Cycle 1; of these, 8 (36%) had an IRR. Among the 20 patients experiencing an IRR, 11 (55%) received ≥1 pre-medication over the course of the study (most commonly: antihistamine, n=6 [30%]; analgesic (paracetamol); n=7 [35%]; steroid, n=6 [30%]). The median time of onset of the first IRR occurrence was at Day 1 (range: 1-22). The median duration of IRRs was 1 day (range: 1-3). Most patients experiencing IRRs (12/20 [60%]) had only one event; 3 (15%) experienced two IRRs and 5 (25%) patients had ≥3 events. Treatment was permanently discontinued due to IRRs in 1 (5%) patient (Grade 3 IRR at first and second infusion); no dose reductions or interruptions/delays occurred due to an IRR. At 13-month follow-up, IRRs were considered recovered/resolved in most (18/20 [90%]) patients (recovered/resolved with sequelae; recovering/resolving, n=1 [5%] each). Conclusions: As expected with biologic treatments administered via IV infusion, IRRs were reported with belamaf in the DREAMM-2 study. However, IRRs were typically mild-to-moderate in severity and most were considered resolved at 13-month follow-up. Importantly, IRRs resulted in few dose modifications or discontinuations, allowing patients to continue active belamaf treatment, which has been associated with durable responses in patients with RRMM. Funding: GSK (Study 205678; drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Disclosures Nooka: Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding; Spectrum Pharmaceuticals: Consultancy; Adaptive Technologies: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding. Lee:Celgene: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Genentech: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding; Regeneron: Research Funding; Genentech: Consultancy; GlaxoSmithKline: Consultancy, Research Funding. Badros:Amgen: Consultancy; University of Maryland: Current Employment. Voorhees:TeneBio: Honoraria, Other: Other relationship; Janssen: Honoraria, Other: Other relationship; Adaptive Biotechnologies: Honoraria, Other: Other relationship; Oncopeptides: Honoraria, Other: Other relationship; Novartis: Honoraria, Other: Other relationship; GSK: Honoraria, Other: Other relationship; BMS/Celgene: Honoraria, Other: Other relationship. Hultcrantz:Intellisphere LLC: Consultancy; Amgen: Research Funding; Daiichi Sankyo: Research Funding; GSK: Research Funding. Karlin:Sanofi: Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; Celgene: Other: Personal fees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees. Arnulf:BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria; Celgene: Research Funding. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. Zhi:GSK: Current Employment, Current equity holder in publicly-traded company. Baron:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Piontek:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Lewis:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Opalinska:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Gupta:Novartis: Current equity holder in publicly-traded company; GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Cohen:Novartis: Other: Patents/Intellectual property licensed, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda,: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Membership on an entity's Board of Directors or advisory committees. Lonial:Karyopharm: Consultancy; Sanofi: Consultancy; Amgen: Consultancy, Honoraria, Other: Personal fees; Takeda: Consultancy, Other: Personal fees, Research Funding; Novartis: Consultancy, Honoraria, Other: Personal fees; Janssen: Consultancy, Honoraria, Other: Personal fees, Research Funding; BMS: Consultancy, Honoraria, Other: Personal fees, Research Funding; GSK: Consultancy, Honoraria, Other: Personal fees; Abbvie: Consultancy; Merck: Consultancy, Honoraria, Other: Personal fees; JUNO Therapeutics: Consultancy; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Honoraria; Genentech: Consultancy; Onyx: Honoraria.

Introduction: Patients with heavily pretreated RRMM have a poor prognosis (median overall survival [OS]: 6-9 months) and a need for novel, well-tolerated treatments that induce lasting responses (Gandhi Leukemia 2019; Chari NEJM 2019). Belamaf (GSK2857916) is a first-in-class, B-cell maturation antigen-targeting, antibody-drug conjugate (ADC) containing monomethyl auristatin F (MMAF). In DREAMM-2 (NCT03525678), patients with heavily pretreated RRMM who responded to single-agent belamaf maintained deep and durable responses at 13-month follow-up (median OS: >13 months) with a manageable safety profile (Lonial ASCO 2020, Poster 436). Consistent with other MMAF-containing ADCs, ocular events were common (Farooq et al. Ophthal Ther 2020). These events included keratopathy (microcyst-like epithelial changes [MECs]: an eye exam finding with/without symptoms), best-corrected visual acuity (BCVA) changes, and symptoms (blurred vision and dry eye). Longer-term recovery data will help inform management strategies. Methods: In DREAMM-2, eye exams were conducted at baseline and prior to each dose in patients received single-agent belamaf (2.5 or 3.4 mg/kg Q3W) and included a corneal exam and assessment of BCVA change from baseline (Snellen visual acuity [VA]). Dose modifications (delays/reductions) were permitted to manage these events. The corneal events were graded per the Keratopathy and Visual Acuity (KVA) scale, which combined corneal exam findings and BCVA changes from baseline. Dose modifications were determined based on the most severe KVA scale grade. These events were followed until recovery, defined as any Grade 1 exam findings/no exam findings, and ≤1-line decline in Snellen VA compared with baseline. A change to a BCVA 20/50 or worse (ie, limiting driving ability) in the better-seeing eye (in patients with BCVA better than 20/50 at baseline) was considered one definition of clinically meaningful VA decrease. Recovery of these events was defined as BCVA improvement to better than 20/50 (better-seeing eye). We report ocular event outcomes for patients receiving belamaf 2.5 mg/kg (recommended dose for future clinical development) from a 13-month follow-up post-hoc analysis. Results: In patients receiving single-agent belamaf 2.5 mg/kg, 72% (68/95) experienced a treatment-related eye exam finding of keratopathy (MECs) (Farooq Ophthal Ther 2020).Fewer patients (56%; 53/95) had symptoms (eg, blurred vision or dry eye) and/or a ≥2-line BCVA decline (better-seeing eye). Treatment discontinuations due to ocular events were rare (3% [3/95] total; 1% [1/95] each due to keratopathy [MECs], blurred vision, and reduced BCVA (Farooq Ophthal Ther 2020). In patients with keratopathy (MEC) events Grade ≥2 per KVA, 48% (29/60) had >1 event. The first event recovered in 77% (46/60; Table; Farooq Ophthal Ther 2020). At last follow-up, 48% (29/60) had documented recovery of their most recent event (Farooq Ophthal Ther 2020). In patients with unrecovered events at last follow-up, 45% (14/31) are receiving treatment or in follow-up. The remaining 55% (17/31) are no longer in follow-up (9 died; 4 withdrew from study; 4 lost to follow-up). 84% (37/44) of patients with Grade 3/4 events were improving or had recovered events at last follow-up. Seventeen (18%) patients had a clinically meaningful BCVA decline, with no reports of complete permanent vision loss (Farooq Ophthal Ther 2020). Of these patients, 76% (13/17) had 1 event and 24% (4/17) had 2 events (no patients had >2 events). 82% (14/17) had recovery of their first event and 82% (14/17) had recovery at last follow-up (Farooq Ophthal Ther 2020). Of the remaining 3 patients with unrecovered events, 1 patient is receiving treatment and 2 patients are no longer in follow-up (1 died due to disease progression; 1 withdrew from study). Conclusions: Though keratopathy (MECs) were frequently observed on eye exam, the majority of patients did not experience a clinically meaningful BCVA decline, and events rarely led to treatment discontinuation. The first keratopathy (MEC) event or clinically meaningful BCVA decline recovered in the majority of patients with events. In this ongoing study, patients are being followed for recovery. Based on experience, it is anticipated these events will likely recover over time. Funding: GSK (205678); drug linker technology licensed from Seattle Genetics; mAb produced using POTELLIGENT Technology licensed from BioWa. Disclosures Lonial: Karyopharm: Consultancy; Sanofi: Consultancy; Amgen: Consultancy, Honoraria, Other: Personal fees; Onyx: Honoraria; Takeda: Consultancy, Other: Personal fees, Research Funding; Novartis: Consultancy, Honoraria, Other: Personal fees; Janssen: Consultancy, Honoraria, Other: Personal fees, Research Funding; BMS: Consultancy, Honoraria, Other: Personal fees, Research Funding; GSK: Consultancy, Honoraria, Other: Personal fees; Abbvie: Consultancy; Merck: Consultancy, Honoraria, Other: Personal fees; JUNO Therapeutics: Consultancy; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Honoraria; Genentech: Consultancy. Nooka:Spectrum Pharmaceuticals: Consultancy; Oncopeptides: Consultancy, Honoraria; Adaptive Technologies: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding. Thulasi:Emory University: Current Employment. Badros:University of Maryland: Current Employment; Amgen: Consultancy. Jeng:Kedrion, Merck, GSK: Consultancy; University of Maryland: Current Employment; EyeGate: Current equity holder in publicly-traded company. Callander:University of Wisconsin: Current Employment; Cellectar: Research Funding. Sborov:University of Utah: Current Employment; Celgene, Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees. Zaugg:University of Utah: Current Employment. Popat:Celgene: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); GSK: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); AbbVie: Consultancy, Honoraria. Degli Esposti:GlaxoSmithKline: Consultancy, Honoraria; Moorfields Eye Hospital: Current Employment. Byrne:Adaptimmune, Novartis: Current equity holder in publicly-traded company; GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Opalinska:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Baron:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Piontek:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Gupta:Novartis: Current equity holder in publicly-traded company; GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Dana:Kala: Consultancy; Alcon: Consultancy; GSK: Consultancy; Aramis Biosciences, Claris Biotherapeutics, GelMEDIX: Current equity holder in private company; Novartis: Consultancy; Dompe: Consultancy; Massachusetts Eye and Ear; Harvard Medical School Department of Ophthalmology: Current Employment; NIH, DOD, Allegan: Current equity holder in publicly-traded company. Farooq:GlaxoSmithKline: Consultancy; University of Chicago: Current Employment. Jakubowiak:Adaptive, Juno: Consultancy, Honoraria; AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Introduction: Single-agent belamaf (GSK2857916), a B-cell maturation antigen-targeting antibody-drug conjugate, demonstrated deep and durable responses with a manageable safety profile in patients with heavily pretreated RRMM (median 7 lines of prior therapy) refractory to an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and refractory and/or intolerant to an anti-CD38 monoclonal antibody in the pivotal Phase II DREAMM-2 study (NCT03525678). At 13-month follow-up, the overall response rate (ORR) was 32% and the median duration of response (DoR) was 11.0 months in the belamaf 2.5 mg/kg arm (Lonial. ASCO 2020 Poster 436). The multimodal mechanism of action, efficacy and safety profile of belamaf, as well as preclinical data suggest possible synergy with standard of care agents and a potential benefit in combination with IMiDs and PIs. DREAMM-6 (NCT03544281) is an ongoing Phase I/II, two-part study of belamaf in combination with lenalidomide/dexamethasone (Arm A) or BorDex (Arm B) in patients with RRMM who had received ≥1 prior therapy (bortezomib-refractory patients were not excluded); preliminary results from Arm B have been reported (Nooka. ASCO 2020 Oral 8502). Methods: Part 1 (dose escalation) and Part 2 (dose expansion) of Arm B in DREAMM-6 evaluated belamaf (2.5 and 3.4 mg/kg intravenously (IV) every 3 weeks [Q3W]) administered as SINGLE (Day 1) or SPLIT dose (divided equally on Days 1 and 8) plus BorDex (Bor 1.3 mg/m2 [subcutaneously] and Dex 20 mg [IV or orally]). Combination treatment continued for up to 8 cycles, with single-agent belamaf maintenance therapy thereafter. Primary objectives were safety, tolerability, and efficacy (ORR [≥ partial response, PR] per investigator-assessed best confirmed response). We report safety and efficacy results from the 2.5 mg/kg SINGLE dose cohort from Arm B. Results: As of March 30, 2020, 18 patients had received belamaf 2.5 mg/kg SINGLE + BorDex in Parts 1 and 2 of Arm B. The median age was 67 years, 61% were male, and 33% had high-risk cytogenetics; patients had received a median of 3 (range, 1-11) prior lines of therapy. All 18 patients had treatment-related adverse events (AEs), of whom 16 (89%) had Grade 3/4 events (see Table). Treatment-related serious AEs occurred in 5 (28%) patients. There were no Grade 5 AEs of interest. Thirteen (72%) patients had dose reductions (8/13 belamaf) and all patients had dose delays (16/18 belamaf) to manage AEs. Five (28%) patients discontinued a study treatment due to AEs: 4 bortezomib, 2 dexamethasone, no patients discontinued belamaf. Of the AEs of interest, thrombocytopenia occurred in 12 patients (67%; maximum Grade 4 in 8 patients and Grade 3 in 3 patients) and led to dose reduction in 6 (33%) patients, dose delay in 7 (39%) patients, and no discontinuations. Three (17%) patients had Grade 2 infusion-related reactions (with no dose modifications or discontinuations). Changes in the corneal epithelium (keratopathy/microcyst-like epithelial changes [MECs], an eye exam finding with or without symptoms), an anticipated AE associated with monomethyl auristatin F, the payload in belamaf, occurred in all 18 patients (maximum Grade 3 in 10 patients, Grade 2 in 7 patients, and Grade 1 in 1 patient), and led to dose reduction in 7 (39%) patients, dose delay in 15 (83%) patients, with no discontinuations. Response was evaluable in all patients; ORR was 78% (95% CI 52.4-93.6), with very good partial response (VGPR) in 9 (50%) and PR in 5 (28%) patients. One (6%) patient had minimal response, and 3 (17%) patients had stable disease. Clinical benefit rate was 83% (95% CI 58.6-96.4). After a median of 18.2 weeks (range 6.0-46.4 weeks) on treatment, median DoR was not reached. Conclusions: The combination of belamaf 2.5 mg/kg Q3W with standard-of care BorDex demonstrated an acceptable safety profile in patients with RRMM who had received a median of 3 prior lines of therapy, with AEs as expected, and no new safety signals to date. Corneal events were common but manageable with belamaf dose modifications. At interim follow-up, best response data indicate a high ORR of 78%, VGPR of 50%, and clinical benefit rate of 83%. Final data for the 2.5 mg/kg SINGLE + BorDex cohort will be reported at the congress. Funding: GSK (Study 207497); drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Disclosures Popat: AbbVie: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Nooka:Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy, Honoraria; Spectrum Pharmaceuticals: Consultancy; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Adaptive Technologies: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding. Stockerl-Goldstein:Celgene: Consultancy; Abbott Laboratories: Current equity holder in publicly-traded company; Abbvie: Current equity holder in publicly-traded company; GSK: Research Funding; Takeda: Research Funding; BiolineRx: Research Funding; Janssen: Research Funding; Cellerant: Other: Other relationship. Abonour:Takeda: Consultancy; Janssen: Honoraria, Research Funding; Celgene: Consultancy; BMS: Consultancy, Research Funding. Khot:Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Other: Speaker fees; Novartis: Other: Travel grant. Lee:Janssen: Consultancy; Amgen: Consultancy; Celgene/BMS: Consultancy. Augustson:Roche: Other: Support of parent study and funding of editorial support. Spencer:AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Honoraria; Amgen, Celgene, Haemalogix, Janssen, Servier and Takeda: Research Funding; AbbVie, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Consultancy; Celgene, Janssen and Takeda: Speakers Bureau. Mateos:Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria; PharmaMar-Zeltia: Consultancy; Abbvie/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Chopra:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Rogers:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Smith:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Davidge:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Montes de Oca:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Ferron-Brady:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Yeakey:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Talekar:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Kremer:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Gupta:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company. Quach:Sanofi: Consultancy, Research Funding; Janssen Cilag: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria, Research Funding; Glaxo Kline Smith: Consultancy, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding.

Introduction: Belamaf (GSK2857916), a B-cell maturation antigen-targeting antibody-drug conjugate (ADC), demonstrated deep and durable responses with a manageable safety profile as a single agent in patients with heavily pretreated RRMM in the pivotal DREAMM-2 study (NCT03525678; Lonial ASCO 2020 Poster 436). Health-related quality of life (HRQoL) was evaluated via the cancer-specific European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC-QLQ-C30; Popat EHA 2020 Poster EP1746), a PRO used extensively in oncology/MM studies to evaluate symptoms, functioning, and QoL. The EORTC-QLQ-MY20 module was used to assess MM symptoms. Corneal events are expected during belamaf treatment, as with other monomethyl auristatin F-containing ADCs, so two ophthalmic vision-related PRO questionnaires (National Eye Institute Visual Function Questionnaire-25 item [NEI-VFQ-25] and Ocular Surface Disease Index [OSDI]) were used to characterize the impact of corneal events on patient symptoms and visual function. Meaningful within-patient changes in OSDI and NEI-VFQ-25 scores were estimated to better interpret outcomes in this population (Eliason ISPOR 2020). We report here the results of the PRO analyses in DREAMM-2 according to measures used in the trial. Methods: In DREAMM-2, patients who received single-agent belamaf (2.5 or 3.4 mg/kg, every 3 weeks [Q3W]) completed PRO questionnaires electronically at baseline and Q3W during treatment. Group-level, mean change from baseline over time was evaluated on EORTC domains. We also evaluated the percentage of patients with ≥10-point meaningful change threshold for improvement (Osoba J Clin Oncol 1998) on EORTC domains over time. Meaningful change thresholds in ocular PROs measuring treatment-related corneal events were estimated using recommended anchor and distribution-based methods, with 12.5-16.6 points estimated as meaningful in this population, depending on the domain (Eliason ISPOR EU 2020). We report results of the PRO data analysis for patients in the 2.5-mg/kg group selected for clinical development. Results: At Weeks 7 and 13, 46% (21/46) and 41% (12/29) of patients who completed PROs improved ≥10 points in the EORTC-QLQ-C30 Fatigue domain score, respectively; 30% (14/46) and 31% (9/29) improved their General Pain domain score. For EORTC-QLQ-C30, there were trends toward improvement in Fatigue at some time points on treatment; Global Health Status (GHS)/QoL, Role Functioning, and Physical Functioning domain scores remained relatively stable. The EORTC-QLQ-MY20 Disease Symptoms domain score (representing pain in different locations) showed a general trend toward improvement over time, with improvements of ≥10 points at Weeks 7 and 13 for 38% (17/45) and 29% (8/28) of participants. Ocular PRO data were available for 95% (92/97) of patients. Based on the OSDI vision-related functioning domain, a total of 49.5% of patients experienced a ≥12.5-point worsening from baseline (median time to worsening: 44 days). Meaningful improvement of these changes (based on defined 12.5-point thresholds) from worst severity post baseline was seen in 72% of patients (median time to improvement: 24 days). Importantly, even among patients with meaningful worsening in visual functioning, patient-reported QoL/GHS, Physical Functioning, and Role Functioning domains of the EORTC-QLQ-C30 remained stable while on treatment (Figure). Conclusions: Disease symptoms, functioning, and QoL did not worsen over time in these heavily pretreated patients receiving belamaf in DREAMM-2. Patients showed a general improvement in fatigue, which is often a difficult-to-manage symptom for patients with RRMM. Group-level, meaningful worsening in vision-related PRO domains was observed, which improved in the majority of patients. Despite ocular symptoms, even in patients with meaningful worsening, EORTC-QLQ-C30 data suggest that overall HRQoL and patient functioning remained stable while on treatment. These PRO results demonstrate a balance between overall QoL/functioning and vision-related impacts that, together with its clinical efficacy, supports the use of belamaf in the treatment of patients with RRMM. Funding: GSK (study 205678); drug linker technology licensed from Seattle Genetics; mAb produced using POTELLIGENT Technology licensed from BioWa. Figure 1 Disclosures Popat: GSK: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Celgene: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); AbbVie: Consultancy, Honoraria. Lonial:Novartis: Consultancy, Honoraria, Other: Personal fees; Takeda: Consultancy, Other: Personal fees, Research Funding; Amgen: Consultancy, Honoraria, Other: Personal fees; Sanofi: Consultancy; Karyopharm: Consultancy; GSK: Consultancy, Honoraria, Other: Personal fees; Abbvie: Consultancy; Merck: Consultancy, Honoraria, Other: Personal fees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; JUNO Therapeutics: Consultancy; Millennium: Consultancy, Honoraria; Onyx: Honoraria; Genentech: Consultancy; Janssen: Consultancy, Honoraria, Other: Personal fees, Research Funding; BMS: Consultancy, Honoraria, Other: Personal fees, Research Funding. Voorhees:Adaptive Biotechnologies: Other: Personal fees; Levine Cancer Institute, Atrium Health: Current Employment; TeneoBio: Other: Personal fees; Oncopeptides: Other: Personal fees; Novartis: Other: Personal fees; Janssen: Other: Personal fees; Celgene: Other: Personal fees; Bristol-Myers Squibb: Other: Personal fees. Degli Esposti:Moorfields Eye Hospital: Current Employment; GlaxoSmithKline: Consultancy, Honoraria. Gupta:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company. Opalinska:GSK: Current Employment, Current equity holder in publicly-traded company. Sapra:GSK: Current Employment, Current equity holder in publicly-traded company. Gorsh:GSK: Current Employment, Current equity holder in publicly-traded company. He:GSK: Current Employment, Current equity holder in publicly-traded company. Kleinman:Triphase Accelerator U.S Corporation: Consultancy; ONL Therapeutics, Inc: Consultancy; Revolution Medicines, Inc: Consultancy; Editas Medicine, Inc: Consultancy; Cleave Therapeutics, Inc: Consultancy; Coherus Biosciences, Inc: Consultancy; Synergy Research Inc: Consultancy; GSK: Consultancy; Eyeon Therapeutics, LLC.: Current equity holder in private company; Zenith Epigenetics Ltd: Consultancy. Schaumberg:Evidera, Inc: Current Employment; GSK: Consultancy; Novaliq: Consultancy; SilkTech: Consultancy; University of Utah School of Medicine: Current Employment. Loubert:Modus Outcomes: Current Employment. Meunier:Modus Outcomes: Current Employment. Regnault:Modus Outcomes: Current Employment. Eliason:GSK: Current Employment, Current equity holder in publicly-traded company.

Introduction: Single-agent belamaf (GSK2857916), a B-cell maturation antigen-targeting antibody-drug conjugate, induced deep and durable responses in patients with RRMM, with a manageable safety profile with 13 months of follow-up (DREAMM-2; NCT03525678; Lonial et al, ASCO 2020, Poster 436). A platform trial design allows efficient evaluation of belamaf in combination with other anti-myeloma agents, such as a humanized wild-type IgG1 anti-OX40 agonist, an IgG4-inducible T-cell co-stimulator (ICOS) agonist, a gamma-secretase inhibitor, and a humanized programmed cell death (PD)-1 antagonist. The unique, multimodal mechanisms of action (MoAs) of belamaf, in combination with MoAs of these agents, has the potential to achieve synergistic effects in RRMM to further enhance anti-myeloma activity without compromising safety. Methods: DREAMM-5 (NCT04126200) is a Phase I/II study that utilizes a master protocol with separate substudies comprised of sequential dose-exploration (DE) and cohort-expansion (CE) phases, to identify promising, effective belamaf combinations when compared with a shared single-agent belamaf control arm (CE phase only). The DE phase consists of multiple dosing cohorts with belamaf combinations in which patients are assigned to treatment slots by a predetermined algorithmic approach (N≤10 per cohort). A recommended Phase II dose (RP2D) for each combination treatment will be identified based on the safety and preliminary efficacy in the DE phase. At the end of the DE phase, an interim analysis of safety, pharmacokinetic, and efficacy data will also be performed for each substudy treatment combination to determine whether the combination should move forward at the RP2D to the CE phase. Patients in the CE phase (N≥35 per cohort) will be randomized to a substudy and within a substudy to either combination treatment or the belamaf monotherapy control arm; patients will also be stratified by number of prior therapies). Eligible patients will have RRMM and will have received ≥3 prior therapy lines, which includes a prior immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody; all patients will provide informed consent for participation. The primary objectives of the study are to identify the RP2D (DE phase) and the overall response rate (≥partial response, CE phase), along with safety and tolerability, for each combination treatment. Substudies 1 (combination with GSK3174998, OX40 agonist antibody), 2 (combination with GSK3359609, ICOS agonist antibody), and 3 (combination with nirogacestat [PF-03084014; SpringWorks Therapeutics], gamma-secretase inhibitor) are currently open to enrollment. Substudy 4 (combination with dostarlimab; PD-1 antagonist antibody) is under review. Additional substudies will be explored based on scientific rationale and/or preclinical combination study results. Funding: GSK (Study 208887); belamaf drug linker technology licensed from Seattle Genetics; belamaf monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa; nirogacestat gamma-secretase inhibitor produced by and used in collaboration with SpringWorks Therapeutics. Figure: DREAMM-5 study design Figure 1 Disclosures Richardson: Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. Nooka:GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding; Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Spectrum Pharmaceuticals: Consultancy; Adaptive Technologies: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding. Quach:Amgen, sanofi, celgene, Karyopharm, GSK: Research Funding; Amgen, Celgene, karyopharm, GSK, Janssen Cilag, Sanofi.: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Consultancy; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Honoraria. Trudel:Celgene, Janssen, Takeda, Sanofi, Karyopharm, Amgen Canada: Honoraria; Celgene, Amgen, GSK: Consultancy, Research Funding; GSK, Celgene, Janssen, Amgen, Genentech: Research Funding. Routledge:Celgene, Sandoz: Consultancy; Amgen, BMS, Celgene, Sandoz: Honoraria. Song:Otsuka: Honoraria; Janssen: Honoraria, Research Funding; Amgen, Celgene,Takeda: Consultancy, Honoraria; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Paul:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Khan:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Brouch:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Ferron-Brady:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Yeakey:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Shelton:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Montes de Oca:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Smith:SpringWorks: Current Employment, Current equity holder in publicly-traded company. Im:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Ahlers:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Paul:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Holkova:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Gupta:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company. Kremer:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Rodriguez-Otero:GlaxoSmithKline: Consultancy, Current Employment, Current equity holder in publicly-traded company, Honoraria; Kite: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Medscape: Membership on an entity's Board of Directors or advisory committees; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Sanofi: Consultancy, Honoraria.

Context: Single-agent belamaf demonstrated deep and durable responses in the DREAMM-2 ( NCT03525678 ) primary analysis (1) and long-term follow-up (2,3). Keratopathy (microcyst-like epithelial changes [MECs] observed on eye examination with/without symptoms) were managed through dose delays and reductions. Objective: To provide an update on the impact of dose delays on responses in patients receiving single-agent belamaf 2.5-mg/kg in DREAMM-2 (13-month follow-up). Methods: In the DREAMM-2 study (single-agent belamaf 2.5 mg/kg [n=97] or 3.4 mg/kg [n=99] Q3W), dose modifications were permitted to manage adverse events (AEs), including keratopathy (MECs), an eye examination finding that may/may not be associated with symptoms. Objective response (IMWG criteria 2016) was assessed by an independent review committee Q3W, regardless of treatment delays. Here, we report a post-hoc analysis on the impact of dose delays >63 days on clinical response in the 2.5-mg/kg arm (the selected dose for future clinical development based on risk–benefit assessment). Results: In patients receiving single-agent belamaf (2.5 mg/kg), dose delays (54%) and reductions (35%) due to AEs were common (2,3). Keratopathy (MECs) was the most frequent reason for dose delays (47%) and reductions (25%), leading to only 1 patient (1%) discontinuing treatment (2,3). Of 31 patients with ≥partial response, 16 had prolonged treatment interruptions (>63 days). Of these 16 patients, 14 (88%) continued experiencing a clinical benefit during the first prolonged delay: 6 (38%) deepened their response during delay (1 SD to MR; 2 PR to VGPR; 2 MR to VGPR; 1 VGPR to CR); 6 (38%) maintained the same response category as that of the last evaluable assessment during delay/first evaluable assessment after delay; 2 (13%) had increasing paraproteins during the delay but did not meet progression criteria. Two (13%) developed disease progression (1 patient 6 weeks into delay; 1 patient 3 weeks after delay). Conclusions: Despite dose delays lasting for several cycles to manage AEs, most responses were sustained throughout the delay, thus maintaining clinical benefit for the majority of patients. Funding: GlaxoSmithKline (205678). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. References: [1] Lonial Lancet Oncol 2020. [2] Lonial ASCO 2020, EP436. [3] Lonial EHA 2020, EP970.

Context: Belamaf showed deep and durable single-agent activity in the pivotal DREAMM-2 study primary analysis ( NCT03525678 ) (1–7) in a patient population that historically has a poor prognosis (overall survival [OS] 6–9 months). Objective: To present longer-term efficacy/safety outcomes (13-month follow-up) with single-agent belamaf in DREAMM-2 in the overall patient population and patients with HR cytogenetics and RI, subgroups with poor outcomes. Methods: DREAMM-2 is an ongoing study of belamaf 2.5 mg/kg (n=97) or 3.4 mg/kg (n=99). Primary outcome: overall response rate (ORR; ≥partial response). In post-hoc analyses, HR-cytogenetics included t(4;14), t(14;16), 17p13del, or 1q21 + . RI was based on eGFR (mild: ≥60– Results: Overall population ORRs in the 2.5 mg/kg and 3.4 mg/kg groups were 32% (97.5% CI: 21.7–43.6) and 35% (97.5% CI: 24.8–47.0); 19% and 23% of patients (58% and 66% of responders) achieved very good partial response or better. Median duration of response was 11.0 (95% CI: 4.2–not reached [NR]) and 6.2 months (95% CI: 4.8–NR). Median progression-free survival was 2.8 (95% CI: 1.6–3.6) and 3.9 months (95% CI: 2.0–5.8); median estimated OS was 13.7 (95% CI: 9.9–NR) and 13.8 months (95% CI: 10.0–NR). Most common Grade ≥3 adverse events (AEs) were keratopathy (microcyst-like epithelial changes [MECs] observed on eye examination; 2.5 mg/kg: 46%; 3.4 mg/kg: 42%), thrombocytopenia (2.5 mg/kg: 22%; 3.4 mg/kg: 32%), and anemia (2.5 mg/kg: 21%; 3.4 mg/kg: 27%). AE-related permanent discontinuation occurred in 9% and 12%; discontinuation due to MECs was rare (2.5 mg/kg: 1%; 3.4 mg/kg: 3%). HR cytogenetics and RI subgroup analyses will be presented at the conference. Conclusions: Deep and durable responses to single-agent belamaf were sustained and no new safety signals identified with longer follow-up in this heavily pretreated RRMM population. Funding: GSK (205678). Drug linker technology licensed from Seattle Genetics; mAb produced using POTELLIGENT Technology licensed from BioWa. References: [1] Lonial et al. Lancet Oncol. 2020. [2] Lonial et al. ASCO 2020. EP436. [3] Lonial et al. EHA 2020. EP970. [4] Cohen et al. ASCO 2020. EP441. [5] Trudel et al. EHA 2020. EP1037. [6] Lee et al. ASCO 2020. EP419. [7] Lee et al. EHA 2020. EP1006.

Summary Background Belantamab mafodotin (GSK2857916), an immunoconjugate targeting B-cell maturation antigen, showed single-agent activity in the phase 1 DREAMM-1 study in heavily pre-treated patients with relapsed or refractory multiple myeloma. We further investigated the safety and activity of belantamab mafodotin in the DREAMM-2 study. Methods DREAMM-2 is an open-label, two-arm, phase 2 study done at 58 multiple myeloma specialty centres in eight countries. Patients (aged ≥18 years) with relapsed or refractory multiple myeloma with disease progression after three or more lines of therapy and who were refractory to immunomodulatory drugs and proteasome inhibitors, and refractory or intolerant (or both) to an anti-CD38 monoclonal antibody with an Eastern Cooperative Oncology Group performance status of 0–2 were recruited, centrally randomly assigned (1:1) with permuted blocks (block size 4), and stratified by previous lines of therapy (≤4 vs >4) and cytogenetic features to receive 2·5 mg/kg or 3·4 mg/kg belantamab mafodotin via intravenous infusion every 3 weeks on day 1 of each cycle until disease progression or unacceptable toxicity. The intention-to-treat population comprised all randomised patients, regardless of treatment administration. The safety population comprised all patients who received at least one dose of belantamab mafodotin. The primary outcome was the proportion of randomly assigned patients in the intention-to-treat population who achieved an overall response, as assessed by an independent review committee. This study is registered with ClinicalTrials.gov , NCT03525678 , and is ongoing. Findings Between June 18, 2018, and Jan 2, 2019, 293 patients were screened and 196 were included in the intention-to-treat population (97 in the 2·5 mg/kg cohort and 99 in the 3·4 mg/kg cohort). As of June 21, 2019 (the primary analysis data cutoff date), 30 (31%; 97·5% CI 20·8–42·6) of 97 patients in the 2·5 mg/kg cohort and 34 (34%; 23·9–46·0) of 99 patients in the 3·4 mg/kg cohort achieved an overall response. The most common grade 3–4 adverse events in the safety population were keratopathy (in 26 [27%] of 95 patients in the 2·5 mg/kg cohort and 21 [21%] of 99 patients in the 3·4 mg/kg cohort), thrombocytopenia (19 [20%] and 33 [33%]), and anaemia (19 [20%] and 25 [25%]); 38 (40%) of 95 patients in the 2·5 mg/kg cohort and 47 (47%) of 99 in the 3·4 mg/kg cohort reported serious adverse events. Two deaths were potentially treatment related (one case of sepsis in the 2·5 mg/kg cohort and one case of haemophagocytic lymphohistiocytosis in the 3·4 mg/kg cohort). Interpretation Single-agent belantamab mafodotin shows anti-myeloma activity with a manageable safety profile in patients with relapsed or refractory multiple myeloma. Funding GlaxoSmithKline.

Interim analyses of a phase I study with GSK2857916, an antibody–drug conjugate against B cell maturation antigen, have previously reported a 60% overall response and 7.9 months progression-free survival in relapsed/refractory multiple myeloma (MM). We provide updated safety and efficacy results of the BMA117159 trial following an additional 14 months' follow-up. This open-label, first-in-human, phase I study was conducted at nine centres in the USA, Canada and the UK, and included adults with MM and progressive disease after stem cell transplantation, alkylators, proteasome inhibitors, and immunomodulators. In part 1, the recommended dose of 3.4 mg/kg was identified; in part 2, patients received GSK2857916 3.4 mg/kg once every 3 weeks. Selected part 2 safety/tolerability and efficacy endpoints are reported. Twenty-one (60.0%; 95% confidence interval (CI) 42.1–76.1) of 35 patients achieved partial response or better, including two stringent complete responses and three complete responses. The median progression-free survival was 12 months and median duration of response was 14.3 months. Thrombocytopenia and corneal events were commonly reported; no new safety signals were identified. GSK2857916 was well tolerated and demonstrated a rapid, deep and durable response in heavily pre-treated patients with relapsed/refractory MM, consolidating the interim analyses conclusions that GSK2857916 is a promising treatment for these patients.

8033 Background: Belantamab mafodotin (GSK2857916; belamaf; BLENREP) is a B-cell maturation antigen (BCMA)-targeting antibody–drug conjugate approved in the US and EU as a monotherapy for the treatment of adult patients with RRMM. Ocular events (OEs) during the pivotal DREAMM-2 trial (NCT03525678) included corneal exam findings (punctate keratopathy and microcyst-like epithelial changes), BCVA changes, and ocular symptoms. Dose reductions or delays based on corneal exam findings and BCVA were used to manage OEs. Here we performed a post hoc investigation of relationships between corneal exam findings, BCVA changes, and patient-reported ocular symptoms to explore if BCVA changes and symptoms could guide dosing, rather than corneal exams. Methods: Eye evaluations (including a corneal exam and BCVA assessment of Snellen visual acuity) were performed on all patients receiving single-agent belamaf (2.5 mg/kg) by ophthalmologists at baseline and prior to each belamaf dose. Changes in the corneal epithelium (Ker) and BCVA were both assessed as per protocol-defined criteria and assessment of grade (Gr) was based on the worse eye. BCVA grading was relative to baseline. Patient-reported ocular symptoms were reported as per the Common Terminology Criteria for Adverse Events. Results: In 12.5% of eye evaluations Gr 3–4 Ker was associated with minimal or no (Gr ≤1) BCVA changes. When patient-reported ocular symptoms were also considered, only 7.5% of evaluations found Gr 3–4 Ker with Gr ≤1 BCVA changes or ocular symptoms. Mild or no (Gr ≤2) Ker was associated with Gr ≤1 BCVA changes in 59.5% of evaluations, or in 38.8% of evaluations with no ocular symptoms reported. Overall, Gr 3–4 Ker were found in 24.9% of evaluations; by contrast, patients had Gr 2–4 BCVA changes or ocular symptoms in 53.7% of evaluations. Association of corneal epithelium changes (Ker) with BCVA changes and ocular symptoms. Conclusions: These findings highlight that BCVA changes and ocular symptoms should be further investigated to determine if they can be used as alternatives (eg, frequency of eye examinations based on symptoms) for the management of belamaf dosing to potentially reduce the burden on patients and healthcare professionals. Clinical trial information: NCT03525678. [Table: see text]

Peripheral ossifying fibroma (POF) is one of the inflammatory reactive exophytic nodular growth, commonly occurring on the gingiva. It is seen more often in females, in the interdental papilla and anterior part of the maxilla. It represents unique clinical characteristics and diverse histopathological features. Surgical excision is the treatment of choice but with a reported recurrence rate of 7%–45%. In the present case report, a 15-year-old female patient reported with the chief complaint of painless swelling in the mandibular anterior region. An excisional biopsy was obtained and sent for histopathological diagnosis. On histopathological examination, it was confirmed as POF. The purpose of this article is to present a case of POF and review the current literature on this condition, so that, such condition can be treated through proper diagnosis and treatment planning.

Patients diagnosed with chronic lymphocytic leukemia (CLL) are usually elderly and frequently have a number of comorbidities. Health-related quality of life (HRQoL) for these patients is of utmost importance and should be taken into consideration when assessing new treatment options. The combination of ofatumumab with chlorambucil has shown longer progression-free survival compared with chlorambucil alone. In this study, we aim to assess how this treatment combination affects patients' health-related quality of life and patient-reported symptoms.In this open-label phase III trial, patients with previously untreated CLL for whom fludarabine-based treatment was contra-indicated, were randomized 1:1 to receive oral chlorambucil (10 mg/mPatient-reported improvements from baseline in Global Health Status (GHS)/HRQoL scores and fatigue scores were recorded during treatment with both chlorambucil monotherapy and ofatumumab in combination with chlorambucil. There were no significant differences between the two treatment arms for GHS/HRQoL (p = 0.667) or fatigue (p = 0.103). Following treatment, numerical improvements to GHS/HRQoL and fatigue scores were reported, with no significant differences between the two treatment arms.Small but detectable improvements in patients' quality of life were reported as a result of treatment. The addition of ofatumumab to chlorambucil did not negatively impact HRQoL. Quality of life was maintained in the months following treatment.

The purpose of this study is to assess the safety and efficacy of the combination of ofatumumab and bendamustine in patients with previously untreated or relapsed chronic lymphocytic leukemia. Patients received IV ofatumumab (cycle 1: 300 mg day 1 and 1,000 mg day 8; cycles 2-6: 1,000 mg on day 1 every 28 days) and IV bendamustine 90 mg m(-2) (previously untreated) or 70 mg m(-2) (relapsed) on days 1 and 2 of each 28-day cycle, for up to 6 cycles. Forty-four previously untreated and 53 relapsed patients were enrolled. Median age was 62.5 years (previously untreated) and 68 years (relapsed); relapsed patients had received a median of 1 (range 1-11) prior therapy. The investigator-assessed overall response rate was 95% (43% complete response [CR]) for the previously untreated, and 74% (11% CR) for the relapsed patients. The regimen was well tolerated with 89% (previously untreated) and 85% (relapsed patients) receiving all 6 cycles. No unexpected toxicities were reported. Grade 3/4 events occurred in 57% of previously untreated, and 72% of relapsed patients. At ∼29 months' follow-up, the median progression-free survival (PFS) was not reached for the previously untreated population, and the 28-month PFS estimate was 72.3%. The median PFS for the relapsed population was 22.5 months (95% CI: 14.0-27.3 months). The combination of ofatumumab and bendamustine was well tolerated and effective in these previously untreated or relapsed populations. Am. J. Hematol. 91:900-906, 2016. © 2016 Wiley Periodicals, Inc.

Introduction: Belantamab mafodotin (belamaf; GSK2857916) is a B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate. In the pivotal Phase II DREAMM-2 study, single-agent belamaf demonstrated deep and durable responses with a manageable safety profile in heavily pretreated patients with RRMM (Lonial et al. Lancet Oncol 2020). Responses were sustained at 13 months of follow-up; with belamaf (2.5 mg/kg administered intravenously [IV] every 3 weeks [Q3W]), overall response rate (ORR) was 32% and median duration of response (DoR) was 11.0 months (Lonial et al. ASCO 2020 Poster 436). Preclinical data suggest synergistic antimyeloma activity of belamaf in combination with pomalidomide/dexamethasone (Pd). Preliminary data from an ongoing Phase I/II study (NCT03715478) evaluating belamaf in combination with Pd (B-Pd) suggest an acceptable safety profile and early signs of clinical activity in patients with RRMM. The DREAMM-8 study (NCT04484623) will evaluate the efficacy and safety of B-Pd compared with pomalidomide, bortezomib, and dexamethasone (PVd). Methods: This Phase III, two-arm, randomized, open-label, multicenter study will include patients with measurable RRMM who have received ≥1 prior line of therapy (including lenalidomide), with documented disease progression during or after their most recent line of treatment. Patients aged ≥18 years with Eastern Cooperative Oncology Group Performance Status 0-2, adequate organ system function, and who provide informed consent will be eligible. Patients with prior exposure to BCMA-targeted therapies or pomalidomide and those intolerant/refractory to bortezomib will be excluded. Approximately 450 patients will be randomized (1:1) to Arm A (B-Pd) or Arm B (PVd), stratified by number of prior lines of treatment, prior exposure to bortezomib, and International Staging System status. No more than 50% of participants with two or more prior lines of treatment will be enrolled. In Arm A, patients will receive belamaf 2.5 mg/kg (IV) Q4W on Day 1 in Cycle 1 (28-day cycle) followed by belamaf 1.9 mg/kg (IV) Q4W on Day 1 in Cycle 2 onwards (28-day cycles); pomalidomide 4 mg (orally [PO]) will be administered on Days 1-21 and dexamethasone 40 mg (PO) on Days 1, 8, 15, and 22 in all cycles (28-day cycles). In Arm B, pomalidomide 4 mg (PO) will be administered Q3W on Days 1-14 in all cycles (21-day cycles); bortezomib 1.3 mg/m2 will be administered subcutaneously on Days 1, 4, 8, and 11 in Cycles 1-8, and Days 1 and 8 in Cycle 9+ (21-day cycles). Dexamethasone 20 mg (PO) will be administered on the day of and the day after bortezomib. The dose level of dexamethasone in each arm will be reduced by half in patients >75 years of age. Treatment in both arms will continue until progressive disease, unacceptable toxicity, withdrawal of consent, initiation of another anticancer therapy, or end of study or death. The primary endpoint is progression-free survival (PFS; time from randomization to the earliest date of documented disease progression or death [any cause]). Minimal residual disease negativity rate is a key secondary endpoint. Additional secondary endpoints include ORR, time to response, DoR, time to progression, overall survival, PFS2 (PFS after initiation of new anticancer therapy), safety, health-related quality of life, and pharmacokinetic and pharmacodynamic parameters. The study is planned to start in August 2020. Funding: GSK (Study 207499); drug linker technology licensed from Seattle Genetics; mAb produced using POTELLIGENT Technology licensed from BioWa. Disclosures Trudel: GSK, Celgene, Janssen, Amgen, Genentech: Research Funding; Celgene, Janssen, Takeda, Sanofi, Karyopharm, Amgen Canada: Honoraria; Celgene, Amgen, GSK: Consultancy, Research Funding. Davis:GSK: Current Employment, Current equity holder in publicly-traded company. Lewis:GSK: Current Employment, Current equity holder in publicly-traded company. Bakshi:GSK: Current Employment, Current equity holder in publicly-traded company. Chopra:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Montes de Oca:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Ferron-Brady:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Eliason:GSK: Current Employment, Current equity holder in publicly-traded company. Kremer:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Gupta:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company. Wu:GSK: Current Employment, Current equity holder in publicly-traded company.

Multiple myeloma (MM) is a hematological malignancy that affects plasma cells and leads to devastating clinical features. Typically, front-line and relapsed/refractory multiple myeloma (RRMM) treatments comprise standard of care (SOC) combinations that include proteasome inhibitors (e.g., bortezomib), immunostimulatory drugs (e.g., lenalidomide or pomalidomide) and/or a steroid (e.g., dexamethasone). While these therapies have significantly improved patient outcomes, the disease remains incurable and novel targeted therapies are urgently needed. Belantamab mafodotin is as a promising candidate for the treatment of multiple myeloma, achieving a 60% overall response rate in a phase 1 clinical trial. Belantamab mafodotin targets the B-cell maturation antigen (BCMA) protein, highly expressed in multiple myeloma and other B cell malignancies. Belantamab mafodotin is an immuno-conjugate that consists of a humanized afucosylated anti-BCMA monoclonal antibody conjugated to the microtubule inhibitor monomethyl auristatin-F (MMAF) that enables anti-tumor activity by: 1) direct cell kill, 2) antibody-dependent cellular cytotoxicity or cellular phagocytosis, and 3) immunogenic cell death. To determine potential combinatorial activity, we conducted in vitro and in vivo studies of belantamab mafodotin in double and/or triple combinations with MM SOC agents (bortezomib, dexamethasone, lenalidomide or pomalidomide) in two multiple myeloma models: OPM-2 and MOLP-8. In vitro, belantamab mafodotin as single agent demonstrated direct cell kill activity in OPM-2 and MOLP-8 cells, after 72 hours of exposure. Treatment of OPM-2 cells with bortezomib, dexamethasone, lenalidomide or pomalidomide also led to direct cell kill. However, direct cell kill of MOLP-8 cells was only observed with bortezomib treatment. Combining belantamab mafodotin with each SOC agent led to synergistic activity in both cell lines. In vivo, belantamab mafodotin significantly induced tumor growth inhibition and provided survival advantage when administered as monotherapy to immune-compromised mice bearing OPM-2 and MOLP-8 xenografts. Combinations with lenalidomide, pomalidomide, or bortezomib enhanced this anti-tumor activity and provided additional survival benefit compared to each single agent. The observed synergy in cell cultures and in vivo xenograft models provided preclinical evidence for combining belantamab mafodotin with IMiDs or bortezomib in MM. Selected combinations are currently under clinical evaluation in RRMM in the DREAMM-6 trial. All studies were conducted in accordance with the GSK Policy on the Care, Welfare and Treatment of Laboratory Animals and were reviewed the Institutional Animal Care and Use Committee either at GSK or by the ethical review process at the institution where the work was performed. Drug linker technology is licensed from Seattle Genetics; monoclonal antibody is produced using POTELLIGENT® Technology licensed from BioWa. Citation Format: Rocio Montes De Oca, Ira Gupta, Chris Shelton. Combinations of belantamab mafodotin with lenalidomide, pomalidomide, bortezomib and/or dexamethasone synergize in vitro and potentiate in vivo anti-tumor activity in multiple myeloma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6711.

8541 Background: Patients with RRMM and HR cytogenetics have a poor prognosis and need effective therapies. In DREAMM-2 (NCT03525678), single-agent belantamab mafodotin (an immunoconjugate targeting B-cell maturation antigen) demonstrated clinically meaningful activity and a manageable safety profile in patients with heavily pretreated RRMM ( Lancet Oncol.2020). We present outcomes in patients with HR-cytogenetics (9-month follow-up). Methods: Patients with RRMM received single-agent belantamab mafodotin (2.5 or 3.4 mg/kg). For this post hoc analysis, HR-cytogenetics included t(4;14), t(14;16), 17p13del, or 1q21+ (tested locally). Results: The median number of cycles was 3 (2.5: range: 1–15) and 4 (3.4: range: 1–14). Overall response rate (ORR; ≥partial response [PR] per independent review committee) was 27% in the 2.5 mg/kg group (22% with ≥very good partial response [VGPR]) and 40% in the 3.4 mg/kg group (27% with ≥VGPR). The median duration of response (DoR) was not reached in the 2.5 mg/kg group and was 6.2 months in the 3.4 mg/kg group. The most common adverse events ( > 30% in either group) were consistent with the overall population ( Lancet Oncol.2020): keratopathy (2.5: 59%;3.4: 79%), thrombocytopenia (2.5: 44%; 3.4: 65%), nausea (2.5: 27%; 3.4: 33%), anemia (2.5: 24%; 3.4: 42%), and blurred vision (2.5: 20%; 3.4: 42%). Conclusions: Patients with HR-cytogenetics maintain deep and durable clinical responses with single-agent belantamab mafodotin, comparable to that reported in the overall population. The safety profile remained consistent with previous reports. Funding: GlaxoSmithKline (205678). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03525678 . [Table: see text]

TPS8552 Background: Single-agent belantamab mafodotin (GSK2857916), a B-cell maturation antigen targeting immunoconjugate, induced deep and durable responses in patients with RRMM, with a manageable safety profile (DREAMM-2, NCT03525678, Lancet Oncol.2020). A platform trial design allows efficient evaluation of belantamab mafodotin in combination with other anti-myeloma agents, such as a humanized wild-type IgG1 anti-OX40 agonist, an IgG4 inducible T-cell costimulatory (ICOS) agonist, and a gamma-secretase inhibitor. The unique, multimodal mechanisms of action (MoAs) of belantamab mafodotin, in combination with MoAs of these agents, has the potential to achieve synergistic effects in MM, to further enhance anti-myeloma activity without compromising safety. Methods: DREAMM-5 (NCT04162210) utilizes a master protocol with separate sub-studies comprised of sequential dose exploration (DE) and cohort expansion (CE) phases, to identify promising, effective belantamab mafodotin combinations when compared with a shared belantamab mafodotin monotherapy control arm (CE phase only). DE phases consist of multiple dosing cohorts with belantamab mafodotin combinations where patients are assigned to treatment slots by predetermined algorithmic approach (modified toxicity probability interval; N≤10 per cohort). Recommended phase 2 doses (RP2D) will be based on dose-limiting toxicities, safety, and pharmacokinetics. Interim analyses, based on overall response rate (ORR), determine if a RP2D is moved forward to a CE phase (N≥35 per cohort). Patients in the CE (stratified by number of prior therapies) will be randomized equally to open sub-studies. Eligible patients will have received ≥3 prior therapy lines which must include ≥1 immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody. The primary objectives are to identify RP2D for each combination (DE phase) and ORR (≥partial response, CE phase). Sub-studies 1 (combination with GSK3174998, OX40 agonist antibody) and 2 (combination with GSK3359609, ICOS agonist antibody) are currently enrolling. Sub-study 3 (combination with nirogacestat [PF-03084014; SpringWorks Therapeutics]) is projected to begin enrollment in the first half of 2020. Additional sub-studies will be explored based on scientific rationale and/or preclinical combination study results. Funding: GlaxoSmithKline (207495). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT04162210 .

8502 Background: Belantamab mafodotin, a B-cell maturation antigen targeting immunoconjugate, demonstrated clinically meaningful, single-agent activity in patients with heavily pre-treated RRMM refractory to an immunomodulatory agent, a proteasome inhibitor, and refractory and/or intolerant to an anti-CD38 monoclonal antibody (DREAMM-2, NCT03525678, Lancet Oncol.2020). The multimodal mechanism of action and manageable safety profile make belantamab mafodotin a promising candidate for use in different RRMM combination regimens. Methods: DREAMM-6 (NCT03544281) is an ongoing, two-part, two-arm, study evaluating the safety, tolerability, and clinical activity of belantamab mafodotin in combination with bortezomib/dexamethasone (BorDex) and lenalidomide/dexamethasone in patients previously treated with ≥1 prior therapy line. Here, we present data for belantamab mafodotin in combination with BorDex. Part 1 (dose escalation) and Part 2 (dose expansion) evaluated belantamab mafodotin (2.5 and 3.4 mg/kg) administered as SINGLE (Day 1) or SPLIT dose (divided equally on Days 1 and 8) in combination with BorDex. Results: As of February 6, 2020, 52 patients were enrolled: 6 patients were enrolled at 2.5 mg/kg single dose and 7 at 3.4 mg/kg single dosing in Part 1, and 45 patients in Part 2. No dose-limiting toxicities were observed. Corneal events (including keratopathy, blurred vision, and dry eye) and thrombocytopenia were the most frequently reported AEs and were clinically manageable. Conclusions: In DREAMM-6, preliminary data demonstrate that the combination of belantamab mafodotin and BorDex has an acceptable safety profile, with no new safety signals identified. Funding: GlaxoSmithKline (207497). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03544281 .

8519 Background: Renal impairment, a frequent complication and poor prognostic factor in RRMM, often leads to poor tolerability of standard regimens. We report outcomes in patients with renal impairment receiving single-agent belantamab mafodotin (2.5 or 3.4 mg/kg; B-cell maturation antigen targeting immunoconjugate not renally metabolized) from the DREAMM-2 post-hoc analysis (NCT03525678). Methods: Eligible patients with RRMM had no active renal conditions and adequate renal function (based on albumin/creatinine ratio [2]: normal [≥90], mild impairment [mild, ≥60≤90], moderate impairment [mod, ≥30≤60]). Results: Overall response rates (95% CI) in patients with mild/mod impairment (2.5 mg/kg: 32% [21.4–44.0]; 3.4 mg/kg: 36% [25.6–48.5]) were similar to those in the overall population ( Lancet Oncol.2020). The median duration of response (DoR) was not reached (NR) in 2.5 mg/kg mild/mod subgroup (95% CI estimate: 4.2 months–NR); median DoR was 7.5 months (4.9–NR) in 3.4 mg/kg mild/mod subgroup. Rates of keratopathy and albuminuria were similar regardless of renal function; rates of anemia, pyrexia, and thrombocytopenia were more frequent in patients with impaired renal function (Table). eGFR did not change or changed to normal in most patients. Conclusions: Following treatment with single-agent belantamab mafodotin, patients with mild/mod renal impairment achieved a similar efficacy and safety profile as patients with normal renal function. Funding: GlaxoSmithKline (205678). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03525678 . [Table: see text]

8536 Background: Single-agent belantamab mafodotin (B-cell maturation antigen targeting immunoconjugate) showed clinically meaningful activity and manageable safety in patients with heavily pre-treated RRMM (DREAMM-2, NCT03525678, Lancet Oncol.2020). We report updated results (median follow-up 9 months). Methods: DREAMM-2 is an ongoing single-agent belantamab mafodotin (2.5 or 3.4 mg/kg) study in patients with RRMM after ≥3 prior therapy lines and refractory to an immunomodulatory agent, a PI, and refractory and/or intolerant to an anti-CD38 mAb. Primary endpoint: overall response rate (ORR; ≥partial response per independent review committee). Results: ORR was 31% in the 2.5 mg/kg (19% with ≥very good partial responses [VGPR]) and 35% (24% with ≥VGPR) in the 3.4 mg/kg groups (Table). Duration of response (DoR) was not reached (NR) in the 2.5 mg/kg and 6.2 months in the 3.4 mg/kg groups; 1-year overall survival (OS) estimate was 53%. Common Grade 3/4 AEs ( > 10% in either group) were keratopathy (2.5: 29%; 3.5: 24%), thrombocytopenia (2.5: 21%; 3.4: 32%), anemia (2.5: 20%; 3.4: 27%), pneumonia (2.5: 6%; 3.4: 13%), and neutropenia (2.5: 11%; 3.4: 16%). AEs were managed with dose delays (2.5: 54%; 3.4: 62%) and reductions (2.5: 34%; 3.4: 43%); discontinuations due to AEs were uncommon (2.5: 9%; 3.4: 12%). Conclusions: Single-agent belantamab mafodotin was well-tolerated, and clinically meaningful responses were sustained despite dose modifications with longer follow-up. Funding: GlaxoSmithKline (205678). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03525678 . [Table: see text]

Treatment for patients with chronic lymphocytic leukaemia who are elderly or who have comorbidities is challenging because fludarabine-based chemoimmunotherapies are mostly not suitable. Chlorambucil remains the standard of care in many countries. We aimed to investigate whether the addition of ofatumumab to chlorambucil could lead to better clinical outcomes than does treatment with chlorambucil alone, while also being tolerable for patients who have few treatment options.We carried out a randomised, open-label, phase 3 trial for treatment-naive patients with chronic lymphocytic leukaemia in 109 centres in 16 countries. We included patients who had active disease needing treatment, but in whom fludarabine-based treatment was not possible. We randomly assigned patients (1:1) to receive oral chlorambucil (10 mg/m(2)) on days 1-7 of a 28 day treatment course or to receive chlorambucil by this schedule plus intravenous ofatumumab (cycle 1: 300 mg on day 1 and 1000 mg on day 8; subsequent cycles: 1000 mg on day 1) for three to 12 cycles. Assignment was done with a randomisation list that was computer generated at GlaxoSmithKline, and was stratified, in a block size of two, by age, disease stage, and performance status. The primary endpoint was progression-free survival in the intention-to-treat population and assessment was done by an independent review committee that was masked to group assignment. The study is registered with ClinicalTrials.gov, number NCT00748189.We enrolled 447 patients, median age 69 years (range 35-92). Between Dec 22, 2008, and May 26, 2011, we randomly assigned 221 patients to chlorambucil plus ofatumumab and 226 patients to chlorambucil alone. Median progression-free survival was 22·4 months (95% CI 19·0-25·2) in the group assigned to chlorambucil plus ofatumumab compared with 13·1 months (10·6-13·8) in the group assigned to chlorambucil only (hazard ratio 0·57, 95% CI 0·45-0·72; p0·0001). Grade 3 or greater adverse events were more common in the chlorambucil plus ofatumumab group (109 [50%] patients; vs 98 [43%] given chlorambucil alone), with neutropenia being the most common event (56 [26%] vs 32 [14%]). Grade 3 or greater infections had similar frequency in both groups. Grade 3 or greater infusion-related adverse events were reported in 22 (10%) patients given chlorambucil plus ofatumumab. Five (2%) patients died during treatment in each group.Addition of ofatumumab to chlorambucil led to clinically important improvements with a manageable side-effect profile in treatment-naive patients with chronic lymphocytic leukaemia who were elderly or had comorbidities. Chlorambucil plus ofatumumab is therefore an important treatment option for these patients who cannot tolerate more intensive therapy.GlaxoSmithKline, Genmab A/S.

Multiple myeloma (MM) is a plasma cell malignancy characterized by clonal proliferation of plasma cells within the bone marrow. B cell maturation antigen (BCMA) is a cell-surface receptor required for the survival of plasma cells and is also ubiquitously expressed on MM cells. Belantamab Mafodotin (GSK2857916) is a humanised monoclonal anti-BCMA antibody, which is afucosylated and conjugated to the microtubule-disrupting agent monomethyl auristatin-F (MMAF). Upon binding to BCMA on the cell surface, belatamab mafodotin is rapidly internalised and the cytotoxic moiety (cys-mcMMAF) is released, leading to direct cell death. BCMA is directly shed from the plasma membrane by gamma-secretase, a type-I sheddase. In order to further enhance belantamab mafodotin activity, we sought to increase cell surface levels of BCMA by blocking shedding of BCMA with a gamma-secretase inhibitor (GSI). We then determined the effect on the activity of belantamab mafodotin by combining belantamab mafodotin with PF-03084014, a highly-selective GSI. In order to understand combination effects against immuno-conjugate activity, a 3-day proliferation assay on a panel of multiple myeloma and lymphoma cell lines with varying levels of BCMA expression was conducted. The assay showed a 50 to 3,000-fold EC50 shift in cell lines sensitive to belantamab mafodotin across multiple lymphoma cell types. Antibody-dependent cellular cytotoxicity (ADCC) activity of belantamab mafodotin in combination with PF-03084014 was also examined. In a 24-hour ADCC Jurkat reporter assay, an EC50 shift across multiple BCMA-expressing cell lines was observed. Even cell lines with very low BCMA expression, such as Raji, showed a synergistic increase in ADCC activity in combination with PF-03084014. Cell lines that were non-responsive in the cell proliferation assay, showed activity in the ADCC assay, indicating low-expressing BCMA cell lines remain sensitive to belantamab mafodotin, alone and in combination with PF-03084014. Synergistic effect from this preclinical work provided rationale to support clinical evaluation of belantamab mafodotin in combination with PF-03084014 in a planned clinical trial (DREAMM-5). Disclosures Eastman: GlaxoSmithKline: Employment, Equity Ownership. Shelton:GlaxoSmithKline: Employment, Equity Ownership. Gupta:GlaxoSmithKline: Employment, Equity Ownership. Krueger:GlaxoSmithKline: Employment, Equity Ownership. Blackwell:GlaxoSmithKline: Employment, Equity Ownership. Bojczuk:GlaxoSmithKline: Employment, Equity Ownership.

Chronic lymphocytic leukemia (CLL) is an incurable disease. Quality of life during treatment and periods of subsequent remission is therefore vital. Health-related quality of life (HRQoL) was compared in relapsed CLL during and after treatment with ofatumumab combined with fludarabine and cyclophosphamide versus fludarabine and cyclophosphamide alone. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 v3 and QLQ-CLL16 were used to assess HRQoL in this open-label, phase 3 study. Improvements in prespecified domains of patient-reported outcomes (Global Health Status [GHS]/HRQoL and B symptom scores) were recorded in both treatment arms after three cycles and were sustained after 18 months of follow-up. The two treatment arms were not significantly different at the nominal 0.05 level for GHS/HRQoL (p = .7278) or B symptoms (p = .5968). Small improvements in quality of life were maintained after therapy. The addition of ofatumumab was without any adverse impact on HRQoL (NC...

In this multicenter, open-label, phase III study, patients with relapsed chronic lymphocytic leukemia (CLL) were randomized (1:1) to receive ofatumumab plus fludarabine and cyclophosphamide (OFA + FC) or FC alone; the primary endpoint being progression-free survival (PFS) assessed by an independent review committee (IRC). Between March 2009 and January 2012, 365 patients were randomized (OFA + FC: n = 183; FC: n = 182). Median IRC-assessed PFS was 28.9 months with OFA + FC versus 18.8 months with FC (hazard ratio = 0.67; 95% confidence interval, 0.51–0.88; p = .0032). Grade ≥3 adverse events (≤60 days after last dose) were reported in 134 (74%) OFA + FC-treated patients compared with 123 (69%) FC-treated patients. Of these, neutropenia was the most common (89 [49%] vs. 64 [36%]). OFA + FC improved PFS with manageable safety for patients with relapsed CLL compared with FC alone, thus providing an alternative treatment option for patients with relapsed CLL. Trial registration: www.clinicaltrials.gov...

6584 Background: In Study 406, the anti-CD20 monoclonal antibody ofatumumab (ofa), given as monotherapy over 6 months, showed 47% overall response rate (ORR) in patients (pts) with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab (FA-ref), or to fludarabine with bulky (>5cm) lymphadenopathy (BF-ref). The effects of ofa retreatment (retx) and maintenance (mt) are unknown. Methods: Pts who responded to ofa and then progressed or had stable disease (SD) in Study 406, were offered retx in Study 416 (NCT00802737; GSK/Genmab) with ofa 1 x 300 mg + 7 x 2000 mg weekly followed by mt with ofa 2000 mg monthly for up to 2 years (if SD or better). Primary endpoint was ORR (1996 NCI-WG). Safety and time to event outcomes were also assessed. Results: Of 29 pts enrolled, 7 had SD and 22 had partial response (PR) and progressed in Study 406. Pts were defined per Study 406: 17 FA-ref, 11 BF-ref, 1 “other”. Pretreatment characteristics were similar between groups. Pts received a median of 12 doses (range 3-32); 86% had 8 doses, 3% received all 32 doses. 72% of pts had infusion-related adverse events (AEs), 41% at 1st infusion, mostly grade 1-2. The most common grade >3 AE occurring up to 60 days after last tx was infection (38%); the most common was pneumonia (17%). 3 pts (10%) had fatal infections, all bronchopneumonia. Clinical efficacy is shown in Table. Comparative analysis to Study 406 is ongoing. Conclusions: The response to ofatumumab (ofa) as induction retreatment and progression-free survival in this limited number of pts was similar to 1st treatment (Study 406). Ofa maintenance had some clinical benefit for pts with advanced CLL. Ofa was well-tolerated with no unexpected toxicities. [Table: see text]