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TPS7591 Background: Patients (pts) with refractory or relapsed (R/R) diffuse large B-cell lymphoma (DLBCL) have poor outcomes with standard treatment. Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca), an antibody-drug conjugate (ADC) comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer toxin, is approved in R/R DLBCL based on data from the phase 2 LOTIS-2 trial (Caimi et al. Lancet Oncol 2021). Rituximab (R) is part of standard immunochemotherapy for DLBCL, both as frontline therapy and in subsequent treatments. Preclinical evidence suggests that the addition of rituximab to anti-CD19 ADC therapy may result in prolonged tumor control (Ryan et al. Blood 2017). LOTIS-5 aims to evaluate Lonca-R vs. standard immunochemotherapy of R + gemcitabine + oxaliplatin (R-GemOx) in pts with R/R DLBCL. Methods: This is a phase 3 randomized open-label, two-part, two-arm multicenter study of Lonca-R in pts with R/R DLBCL (NCT04384484). A review of safety data from the nonrandomized safety run-in (Part 1), comparing the safety of Lonca-R to previous Lonca safety data, was completed in January 2022. The trial is now continuing to the randomized phase (Part 2). In Part 2, approximately 330 pts will be randomized 1:1 to receive Lonca-R or R-GemOx. The primary objective of the study is to evaluate the efficacy of Lonca-R versus R-GemOx. The primary endpoint is progression-free survival by independent central review (ICR). Secondary endpoints include overall survival, overall response rate (by ICR using 2014 Lugano classification), complete response rate by ICR, duration of response by ICR, frequency and severity of adverse events, changes from baseline in safety laboratory and clinical variables, concentration and pharmacokinetic parameters of Lonca (conjugated and total antibody and unconjugated warhead), immunogenicity, and changes in patient-reported outcomes. The time to event endpoints will be analyzed based on the intent-to-treat population using a stratified log-rank test. The dosing regimen for Lonca-R: Lonca at 0.15 mg/kg + rituximab at 375 mg/m2 every 3 weeks (Q3W) for 2 cycles and then Lonca at 0.075 mg/kg + rituximab at 375 mg/m2 Q3W for up to 6 cycles. The dose regimen of R-GemOx: rituximab at 375 mg/m2, gemcitabine at 1000 mg/m2 Gem, and oxaliplatin at 100 mg/m2 every 2 weeks for up to 8 cycles. Key inclusion criteria include age ≥18 years, pathologic diagnosis of DLBCL (including pts with DLBCL transformed from indolent lymphoma) or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, ≥1 line of prior systemic therapy, not being a candidate for stem cell transplantation, and measurable disease per the 2014 Lugano classification. The randomized part of LOTIS-5 commenced in January 2022, and recruitment is ongoing. Funding: ADC Therapeutics SA; medical writing: CiTRUS Health Group. Clinical trial information: NCT04384484.

e19551 Background: Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca) is an FDA approved CD19-directed antibody-drug conjugate for R/R DLBCL. From the LOTIS-2 trial primary data cut (April 6, 2020), overall response rate was 48.3% and median overall survival (OS) was 9.9 months. The OS Kaplan-Meier (KM) plot displayed a survival plateau suggesting the presence of long-term survivors (LTS). Survival analyses were conducted on a more mature data cut (March 1, 2021; median follow-up = 1.7 years, follow-up completeness at median = 81%) to estimate the percentage of LTS and expected lifetime survival (mean OS) for lonca-treated patients. Methods: Consistent with studies of other R/R DLBCL treatments, identified through a literature review, parametric and mixture cure models were fit utilizing multiple distributions. Flexible cubic spline (hazard scale 1-3 knots) and non-mixture cure analyses were also conducted. Age- and gender-matched United States life table hazards were used in projections for LTS and to ensure modeled hazards were not less than the general population. Best-fit models were determined through fit statistics, KM and fitted curve overlays, and clinical plausibility. The best-fit model from each method was a candidate for overall best fit. A hybrid model following the best-fit parametric/spline model to a defined time point and switching to general population mortality was also constructed. Results: Mixture and non-mixture cure models fit best (individual best fits gamma and Weibull, respectively). Parametric and spline models (individual best fits log-normal and 2 knot models, respectively) did not fit the observed data well nor fit the clinical expectation of long-term survival. Due to better fit, spline models were used in the hybrid model. LTS from the mixture cure and non-mixture cure models were 24-26%. Mixture cure, non-mixture cure, and hybrid model with a 2-year switch point were consistent in survival predictions (6.11-6.23 years). In a sensitivity analysis with 3-year switch point in the hybrid model, the estimated survival was shorter due to the switch point being below the observed survival plateau. Table presents full survival results and fit statistics. Conclusions: The observed survival plateau suggests lonca-treated patients may include LTS. Mixture cure, non-mixture cure, and hybrid models fit the trial data well and align on survival projections (6.11-6.23 years). Additional follow-up may help refine the switch point of the hybrid model and confirm presence of LTS.[Table: see text]

7546 Background: Outcomes for patients with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) are poor, particularly for those with high-risk clinical characteristics. There remains an unmet need for new treatment options for these patients. Loncastuximab tesirine (Lonca) is an antibody-drug conjugate comprising a humanized anti-CD19 antibody conjugated to a potent pyrrolobenzodiazepine dimer toxin. LOTIS 2 was a pivotal Phase 2 study that demonstrated substantial single-agent anti-cancer activity of Lonca in patients with R/R DLBCL. Efficacy and safety data were presented at ASH 2020 (Caimi et al, ASH 2020; abstract 1183). Here we present subgroup analyses of duration of response (DoR) to Lonca by demographic and clinical characteristics. Methods: Adult patients with R/R DLBCL who had received ≥2 prior therapies were enrolled in this Phase 2, multicenter, single-arm, open-label study of single-agent Lonca (150 µg/kg every 3 weeks for 2 doses, followed by 75 µg/kg thereafter for up to 1 year). The primary analysis has previously been reported, with a primary endpoint of overall response rate (ORR). Patients are being followed-up every 12 weeks for up to 3 years. DoR was a key secondary efficacy endpoint, defined as time from the first documentation of response (central review) to disease progression or death. We analyzed pre-specified demographic and clinical characteristic subgroups for DoR. Results: As of data cut-off (August 6, 2020), ORR in the total population (N = 145) was 48.3% (24.8% had complete response [CR] and 23.4% had partial response [PR]). Median DoR (mDoR) for the 70 responders was 12.58 months. mDoR for patients with CR and PR was 13.37 months and 5.68 months, respectively. Overall, subgroups with high-risk characteristics for poor prognosis had a DoR comparable to the whole study population. mDoR for patients with double-/triple-hit DLBCL was 13.37 months, with advanced stage disease was 12.58 months, and with transformed disease was 12.58 months. The mDoR for older patients was longer than for younger patients (≥75 years, 13.37 months; 65 to < 75 years, 12.58 months; < 65 years, 9.26 months). Patients with DLBCL refractory (defined as no response to therapy) to first-line, most recent line, and all prior lines of therapy had mDoRs of 9.63 months, 9.26 months, and 9.63 months, respectively. Conclusions: Durable responses were observed with the recommended Phase 2 dose regimen of Lonca in heavily pre-treated patients and those at high risk of poor prognosis, including older patients and those with double-/triple-hit, advanced stage, transformed, and primary refractory DLBCL. Updated DoR data will be presented at the meeting. Clinical trial information: NCT03589469.

7519 Background: Glofitamab (RG6026), a T-cell-engaging, bispecific, full-length antibody, allows bivalent binding to CD20 (B-cells), and monovalent binding to CD3 (T-cells). In NP30179 (NCT03075696), an ongoing multicenter, Phase I dose-escalation and expansion study, 0.6–25mg glofitamab fixed-dosing with obinutuzumab pretreatment (Gpt), showed high, durable complete responses and manageable safety in heavily pretreated R/R NHL (Dickinson, et al. EHA 2020). Glofitamab SUD, in addition to Gpt, allowed dose escalation up to 30mg to maximize efficacy, while mitigating cytokine release syndrome (CRS) (Hutchings, et al. JCO 2021). We present updated efficacy data from glofitamab monotherapy SUD cohorts. Methods: Gpt (1000mg) was given to pts 7 days pre-glofitamab initial dose. Intravenous SUD of glofitamab was given on Day (D) 1 and 8 of Cycle (C) 1 and then at the target dose from C2D1 (2.5/10/16mg or 2.5/10/30mg); treatment continued for up to 12 cycles, every 21 days. Response rates were based on the Lugano criteria (Cheson, et al. JCO 2014). Results: Fifty-two pts received glofitamab SUD; 17 and 35 pts received 2.5/10/16mg and 2.5/10/30mg, respectively. Twenty-eight pts (53.8%) had aggressive NHL (aNHL) and 24 pts had indolent NHL (iNHL). Pts had a median age of 68 (44–85) years and received a median of 3 (1–12) prior lines of therapy. Forty (76.9%) and 38 (73.1%) pts were refractory to their most recent and any prior CD20 therapy, respectively. After a median follow-up of 6.3 months, an updated efficacy analysis was conducted on December 1, 2020. For pts with aNHL (N = 28), the best overall response (OR) and complete metabolic response (CMR) rates were 64.3% and 57.1%, respectively; a trend of improved response was observed with increased target dose, with a CMR rate of 71.4% at 2.5/10/30mg (N = 14). Notably, 4/5 pts (80%) with mantle cell lymphoma (2.5/10/16mg, n = 2; 2.5/10/30mg, n = 2) had CMR. For aNHL, 13/16 CMRs are ongoing, with 8 CMRs lasting > 3 months. For pts with iNHL (N = 24), OR and CMR rates were 79.2% and 70.8%, respectively; 14/17 CMRs are ongoing, with 10 CMRs lasting > 3 months. As of August 3, 2020, common adverse events (52 pts) were CRS (63.5%), neutropenia (38.5%), and pyrexia (32.7%). CRS was mostly confined to C1: 24/50 pts had CRS after 2.5mg; 20/49 pts after 10mg; 2/16 and 8/32 pts had CRS after 16 and 30mg (C2D1), respectively. Grade [Gr] 1 and 2 CRS was reported in 18 (34.6%) and 12 (23%) pts, respectively; 3 pts had Gr 3 CRS; none had Gr 4/5 events (ASTCT 2019). Updated data, including biomarker data on baseline CD20 expression and CD8 levels in the tumor, will be presented. Conclusions: Updated data for glofitamab monotherapy SUD show higher preliminary response rates than previously reported in pts with R/R NHL who have failed multiple lines of therapy. CRS was mostly manageable, of low grade, and confined to the first cycle of treatment. Clinical trial information: NCT03075696.

TPS7574 Background: Patients (pts) with DLBCL for whom frontline therapy is unsuccessful and who are ineligible for autologous stem cell transplantation have poor outcomes with salvage therapy. Single-agent loncastuximab tesirine (Lonca), an antibody-drug conjugate comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer (PBD) toxin, showed antitumor activity and manageable toxicity in pts with R/R B-cell non-Hodgkin lymphoma in a Phase 1 trial (Hamadani et al. Blood 2020; blood.2020007512) and in pts with R/R DLBCL in a Phase 2 trial (Caimi et al. Blood 2020; 136(Suppl 1):35–37). Rituximab (R) is part of standard immunochemotherapy for DLBCL, both as frontline therapy and in subsequent treatments. LOTIS-5 aims to evaluate Lonca + R (Lonca-R) versus (vs) standard immunochemotherapy of R + gemcitabine + oxaliplatin (R-GemOx) in pts with R/R DLBCL. Methods: This is a Phase 3 randomized, open-label, 2-part, 2-arm, multicenter study (NCT04384484). A non-randomized safety run-in (Part 1) will compare the safety of Lonca-R with previous safety data for Lonca after the first 20 pts have completed Cycle 1. Part 2 will be started if no significant increase in toxicity occurs; ̃330 pts will be randomized 1:1 to receive Lonca-R or R-GemOx. The primary objective of the study is to evaluate the efficacy of Lonca-R vs R-GemOx. The primary endpoint is progression-free survival by independent review. Secondary endpoints include overall survival; objective response rate; complete response rate; duration of response; frequency and severity of adverse events; changes from baseline in safety laboratory and clinical variables; concentration and pharmacokinetic parameters of Lonca (conjugated and total antibody, and unconjugated warhead); immunogenicity; and changes in patient-reported outcomes. Time-to-event endpoints will be assessed for the intent-to-treat population using a stratified log-rank test. The dosing regimen of Lonca-R in both parts of the study will be 150 µg/kg Lonca + 375 mg/m2 R every 3 weeks (Q3W) for 2 cycles and then 75 µg/kg Lonca + 375 mg/m2 R for 6 cycles. The dose regimen of R-GemOx in Part 2 will be 375 mg/m2 R, 1000 mg/m2 Gem, and 100 mg/m2 Ox Q2W for 8 cycles. Key inclusion criteria include age ≥18 years; pathologic diagnosis of DLBCL (including pts with DLBCL transformed from indolent lymphoma) or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; ≥1 line of prior systemic therapy; not a candidate for stem cell transplantation; and measurable disease per 2014 Lugano Classification. The study opened in September 2020 and enrollment is ongoing. The trial design was presented at 62nd American Society of Hematology Annual Meeting and Exposition, December 5–8, 2020. Research Funding: ADC Therapeutics SA. Clinical trial information: NCT04384484.

170 Background: While there are different studies investigating the quality of life (QoL) of cancer patients (pts) during active treatment, few studies report QoL of cancer survivors (CS) after at least 5 years (yrs) from achieving complete remission. We have investigated QoL and concerns about physical\psychological symptom of CS enrolled in our survivorship program from April 2015 to December 2016. Methods: We included pts > 18 yrs affected by hematologic or solid tumors after at least 5 yrs from achieving complete remission. A cross-sectional survey was carried out using validated scales: Cancer Survivors Survey of Needs subscale and a single-item measure of global QoL perception. Results: We analyzed data from 178 CS. The median age was 62 yrs (52 yrs at diagnosis), 70% were females. The most frequent histological types were breast (50%), colorectal (11%) and hematologic tumors (16%). Most pts received both chemotherapy and radiation therapy. With a median observation time of 139 months, the 10-yrs cumulative incidence of second neoplasm and cardiac adverse event was 8% and 7% respectively. 133 pts (65%) reported a good QoL (score > 3). The most frequent symptoms reported were weight changes (77%), memory\concentration deficit (65%), dental\mouth problems (61%). The most common physical\psychological symptoms were fear of relapse (83%), genetic counseling (68%), living with uncertainty (66%). A positive statistically significant association (p < 0.05) was observed between previous hormonal therapy and the following concerns (score ≥2): sleep disturbance (42% vs 35%); weight gain (31% vs 24%), osteoporosis (35% vs 18%), living with uncertainty (44% vs 38%). Female reported more fear of relapse (p 0.023) and sense of uncertainty (p 0.006) than males. 92% of pts have fully or partially adhered to the survivorship care plan. Conclusions: Most CS have a good QoL perception but we observed a high percentage of pts with a low score indicating different needs to be addressed. Pts treated with hormonal therapy are at higher risk of having both physical and psychological concerns. So far, the compliance of pts with the program was high.

NOTE. Median follow-up, 5.7 years (range, 1-8.7); Z-HDS, 5.9 (range, 1-8.3); HDS, 4.9 (range, 1.4-8.7).

40 Background: In our Institution, we started a survivorship care program that integrates survivors’ health care provided by the oncologist and the primary care physician (PCP).We present the follow-up analysis of the first cohort of patients (pts) enrolled from April to July 2015. Methods: We included adult pts affected by hematologic or solid tumors without evidence of disease from at least 5 years (yrs). They are referred to the PCP with a survivorship care plan. An online platform for cancer survivors (CS) and their PCPs will be available. Progression free survival (PFS), overall survival (OS) and treatment related clinical events were calculated after 17 months from the start of the project. Results: We analyzed data from 269 CS. The median age was 67 yrs, they were mainly females (77%). The most frequent histological types were breast (157), colorectal (37), and hematologic (30) tumors. 189 pts had an early stage disease. 161 pts received chemotherapy with 95 pts receiving anthracycline-based-chemotherapy (ABC), 86% at a cumulative dose > 240 mg/mq. 154 pts underwent radiation therapy (RT), 94% at a dose > 30 Gy. 58 pts received both ABC and RT. The 10-yr cumulative risk of secondary cancer (SC) was 4% with a median latency period from the first cancer diagnosis of 11.3 yrs. 15-yr OS was 98% (one patient died of myocardial infarction), and 15-yr PFS was 96%. The 10-yr cumulative risk of late cardiologic toxicity (LCT) was 11% and 37 pts developed cardiologic complications with a median latency period from treatment of 10.5 yrs. The adhesion to the survivorship care plan was 84%. 13% of pts returned to our Center. The main non-clinical reason for returning was the lack of confidence in PCP. No association was observed between ABC and/or RT exposure and LCT or SC development. Conclusions: In this cohort of patients a high risk of LCT was observed. The risk and latency of SC was similar to the ones reported in literature. The number of cardiac events and SC is too low to give solid conclusions about the association with therapeutic exposure. So far, the compliance of patients and PCPs with the program was high. More data and longer follow-up period are necessary to confirm the accuracy of this model of care.

e275 Background: The population of cancer-survivors faces different lifetime health risk. Thus, models for high-quality and personalized care delivery are strongly needed. ASCO provides different models for survivorship care delivery but there is not an agreement on what is the best in meeting patients’ needs and in terms of cost-effectiveness. In our institution we started a program that tries to integrate survivors’ health care provided by the oncologist and by the Primary Care Physician (PCP). Methods: We included patients (pts) aged more than 18 yrs-old at the time of diagnosis, affected by hematologic or solid tumors. Pts had no evidence of disease from at least 5 yrs from the diagnosis. They are referred to the PCP with the following documents: Survivorship Care-Plan, Survivorship Care-Program, letter to the PCP. Recurrence rate, death rate, treatment related serious clinical events will be calculated after 12 months from the start of the project. Results: We includedin our program 269 cancer-survivors (60% of pts referred to our survivorship-clinic from April to July 2015). The median age was 67 yrs, they were mainly females. The different cancer types were: breast (157), colorectal (36), hematologic (30), gynecologic (11), gastric (9), melanoma (6) lung (5), genitourinary (5), head/neck (3), sarcoma (3) and others (4). 189 of pts had an early stage disease (stage I-II) at diagnosis. 234 of pts underwent surgical treatment and 161 received chemotherapy with different schedules based on tumor types. 59% of pts received anthracycline-based-chemotherapy, 78% at a cumulative dose > 240 mg/m2 . 154 of pts underwent radiation therapy (90% in thoracic field) with a median dose of 60 Gy. We observed 11 cases of secondary cancer after a median of 2.7 yrs from the first diagnosis. The median observation time from the diagnosis to the inclusion in our program was 10 yrs (range 2-31). Conclusions: The observation period from the beginning of the program is too short to provide follow-up data. A high percentage of pts present a high risk of cardiologic late toxicities, therefore they need a more intensive cardiologic follow-up. We will present the first follow-up analysis of this cohort of pts in April 2016.

e13593 Background: Sorafenib might have a role in the treatment of malignant lymphomas by overcoming the cytoprotective effects of Bcl-XL, ERK, and Mcl-1 and eventually targeting additional signalling pathways relevant to lymphomagenesis. This Phase II study was aimed to determine safety and activity of Sorafenib in patients (pts) with refractory/relapsed malignant lymphomas. Methods: Between March 2008 and July 2010, 30 pts (M/F: 19/11; median age, 61 years; range, 18-74) with relapsed (n = 6) or refractory (n = 24) aggressive non-Hodgkin lymphoma (NHL) (n = 14), indolent NHL (n = 7), chronic lymphocytic leukemia (n = 2), peripheral T cell NHL (n = 1) and Hodgkin Lymphoma (n = 6) were enrolled in this study. Prior to study entry, pts received a median of 4 (range, 1-8) lines of treatment with autografting performed in 67% and an additional allografting in 17% of cases. Sorafenib 400 mg BID was administered continuously until disease progression or appearance of clinical significant toxicity. Tumor respon...

8019 Background: ASCT is the procedure of choice in poor risk NHL, however conditioning regimens is a challenging procedures because safely delivered only in younger and clinically fit patients, th...

e18513 Background: We reported that dendritic cell-based vaccination in relapsed indolent NHL patients achieved clinical benefits strongly associated with B and T cell responses. Hence, we exploited the antibody (Ab) repertoires of responders (R) and non-R (NR) to investigate whether the recognized ags might represent novel NHL targets for therapy. Methods: Vaccine-induced Ab cross-reactivity with allogeneic paraffin-embedded specimens and live tumor cells was tested by immunohistochemistry (IHC) and flow cytometry (FC), using biotinylated Abs purified from pre- and post-vaccine sera. Ag discovery was performed by a modified serological proteomics- based approach. Proteins differentially revealed by post-vaccine Abs of R were analyzed by mass spectrometry (MS). Abs-mediated antitumor activity of was tested in a standard proliferation assay. Statistical analysis was performed by Student t-test. Results: Post-vaccine Abs from R displayed increased allo-reactivity compared to matched pre-vaccine or NR sample...

3068 Background: Encouraging safety and clinical activity of givinostat (ITF2357, Italfarmaco, Italy, EU) in combination with the alkylating agent meclorethamine observed in a compassionate use tri...

7567 Background: The aim of this retrospective study was to evaluate with a long follow-up the efficacy of HDCT + ASCT or ABMT for refractory or relapsed HL. Methods: Data were collected from 99 pts who failed or relapsed after first-line CT± radiotherapy and were treated with HDCT+ASCT or ABMT between Oct 1984 and Dec 2003. Thirty-two pts had late relapse (CR≥12 months), 31 had early relapse (CR No significant financial relationships to disclose.

9589 This study was aimed at investigating the development of T cell-mediated immune response in B cell tumor patients and at defining the optimal conditions for developing adoptive immunotherapy p...