Search

Steroid-refractory chronic graft versus host disease (cGVHD) remains a significant cause of morbidity and mortality following allogeneic transplantation. Abatacept is a selective co-stimulation modulator, used for the treatment of rheumatologic disease, and was recently the first drug to be approved by the FDA for the prophylaxis of acute graft versus host disease. We conducted a Phase II study to evaluate the efficacy of Abatacept in steroid-refractory cGVHD (clinicaltrials.gov #NCT01954979). The overall response rate was 58%, with all responders achieving a partial response. Abatacept was well-tolerated with few serious infectious complications. Immune correlative studies showed a decrease in IL-1-alpha, IL-21, and TNF-alpha as well as decreased PD-1 expression by CD4+ T cells in all patients after treatment with Abatacept, demonstrating the effect of this drug on the immune microenvironment. The results demonstrate that Abatacept is a promising therapeutic strategy for the treatment of cGVHD.

Introduction: Our group has pioneered a novel vaccine by fusion of patient-derived tumor with autologous dendritic cells (DCs) that presents an array of tumor antigens generating a polyclonal immune response. DC/AML vaccination led to expansion of leukemia-specific T cells with survival benefit in a phase II clinical trial. We postulated that ex vivo generation of vaccine-educated T cells would provide a powerful platform for adoptive immunotherapy with opportunity to augment T-cell functional potency prior to infusion. We report on an ex vivo system in which vaccine-educated T cells are further enriched for activated antigen-specific effector cells via an agonistic 4-1bb antibody. We report phenotypic and functional characteristics of 4-1bb-enriched vaccine-educated T cells. Methods: DC/AML fusion vaccines were generated from C57BL/6J mice DCs and syngeneic C1498 mCh/luc+ AML cells. Splenic T cells were co-cultured with autologous irradiated DC/AML fusions in presence of IL-2/7/15. Selection with biotinylated agonistic 4-1bb (3H3) was performed on vaccine-educated T cells followed by expansion with anti-CD3/CD28 activation beads. T cells were phenotyped for activation (CD25/CD69), immune checkpoints (PD1/LAG3/TIM3), memory (CD44+CD62L-) and enrichment (anti-rat H&L). Cytotoxicity was evaluated by luminescence. Mice were inoculated with C1498 and injected with T cells 7 days later. BLI imaging was performed and 100-day survival measured. Results: Vaccine-educated T cells demonstrated evidence of immune activation and memory phenotype compared to unstimulated naïve T-cell controls (TN) (7.24-fold, CD4+CD25+CD69+; 1.7-fold, CD3+CD44+CD62L-). Vaccine-educated T cells selected based on 4-1bb expression showed enhanced markers of activation (15.3-fold, CD4+CD25+CD69+) and memory phenotype (5-fold, CD3+CD44+CD62L-) compared to TN. Selection enriched for 4-1bb+ vaccine-educated T cells resulting in enhanced antigen-specific recognition as measured by tumor lysate induction of IFNg expression. Tumor specificity and activation was maintained following CD3/CD28-mediated expansion. The 4-1bb+ vaccine-educated T cells showed enhanced cytotoxicity (1.9-fold increase/TN at 10:1 E/T, P Conclusion: We demonstrate that vaccine-educated T cells subject to selection via an agonist 4-1bb antibody confer enhanced tumor selectivity and potency. Optimal duration for T-cell education was 3-5 days. T-cell stimulation and enrichment by agonistic 4-1bb selection enhanced cytotoxicity and memory phenotype. Thus, 4-1bb selection is a novel approach for antigen-specific T-cell enrichment for superior adoptive immunotherapy in AML. Citation Format: Kathrine S. Rallis*, Jessica Liegel*, Giulia Cheloni, Dina Stroopinsky, Poorva Bindal, Kenel Dufort, Daniela Torres, Isabella Saldarriaga, Samuel Herzlinger, Abigael Morin, Raphael Kesselman, Jeremy Rosenbaum, Georges Chedid, Sophia Adamia, Donald Kufe, Jacalyn Rosenblatt, David Avigan. 4-1bb selection augments DC/AML fusion vaccine-educated T cells for adoptive cell therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4076.

PURPOSE: Evidence suggests that patients with cancer frequently use cannabis with medicinal intent and desire clinical guidance from providers. We aimed to determine whether oncology training adequately prepares fellows to discuss medical cannabis. METHODS: A national survey study was conducted from January to March 2021. A questionnaire assessing oncology fellows' practices regarding cannabis recommendations in cancer care and their knowledge of its effectiveness and risks compared with conventional care for cancer-related symptoms was developed and sent to 155 US-based oncology training programs to distribute to trainees. RESULTS: Forty programs from 25 states participated; of the 462 trainees across these programs, 189 responded (response rate of 40%). Of the participants, 52% were female; 52% were White, 33% Asian, and 5% Hispanic. Fifty-seven percent reported that they discussed medical cannabis with more than five patients in the preceding year; however, only 13% felt sufficiently informed to issue cannabis-related clinical recommendations. Twenty-four percent reported having received formal training regarding medical cannabis. Oncology fellows who reported having received prior training in medical cannabis were significantly more likely to discuss cannabis with patients (risk ratio: 1.37, 95% CI 1.06 to 1.75; P = .002) and feel sufficiently informed to discuss cannabis recommendations (risk ratio: 5.06; 95% CI, 2.33 to 10.99; P < .001). Many viewed the botanical as a useful adjunctive therapy that was at least as effective as conventional treatments for anorexia/cachexia (72%), nausea/vomiting (45%), and pain (41%). CONCLUSION: Most oncology trainees not only reported engaging in discussions regarding medical cannabis with patients but also considered themselves insufficiently informed to make cannabis-related clinical recommendations. The discrepancy between the frequency of cannabis inquiries/discussions at the patient level and comfort/knowledge at the trainee provider level represents an unmet curricular need with implications for both graduate medical education and patient care.

Introduction Immune agents including anti-programmed death receptor-1 and anti-cytotoxic T-lymphocyte antigen-4 have been associated with numerous immune-related complications. Pembrolizumab, a programmed death-1 inhibitor, has been associated with a number of immune-related adverse events such as pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and type 1 diabetes. Case report We present a rare case of an elderly male on pembrolizumab who suffered from four autoimmune toxicities including type 1 diabetes, pneumonitis, hypothyroidism, and polymyalgia rheumatica likely catalyzed by age-related immune activation. Management and outcome: Immunotherapy was indefinitely stopped, and patient was started on steroids for the immune-related adverse events with complete resolution of polymyalgia rheumatica. Thyroid dysfunction resolved once he started thyroid replacement therapy. His diabetes is well controlled with insulin and is followed by endocrinology. He continues on prednisone for immune-mediated pneumonitis with a good response with regular monitoring via computed tomography scans and pulmonary consultation. Discussion Few cases wherein multiple toxicities are seen within one patient are reported. Aging appears to be a risk factor for immune-related adverse events. Aging is associated with an increased incidence of autoimmunity as programmed death-1 ligand expression represents an important mechanism that tissues use to protect from self-reactive effector T cells. Programmed death-1 blockade breaks this protective mechanism and enhances autoimmune diseases. Therefore, close monitoring and extreme vigilance is warranted while using immune checkpoint inhibitors including pembrolizumab as multiple toxicities can occur within a short span of infusion, especially in elderly individuals. Prompt discontinuation and the use of a multidisciplinary team are prudent to prevent further morbidity and mortality.

Atezolizumab (a monoclonal antibody against PD-L1), which restores anticancer immunity, improved overall survival in patients with previously treated non-small-cell lung cancer and also showed clinical benefit when combined with chemotherapy as first-line treatment of non-small-cell lung cancer. IMpower130 aimed to assess the efficacy and safety of atezolizumab plus chemotherapy versus chemotherapy alone as first-line therapy for non-squamous non-small-cell lung cancer.IMpower130 was a multicentre, randomised, open-label, phase 3 study done in 131 centres across eight countries (the USA, Canada, Belgium, France, Germany, Italy, Spain, and Israel). Eligible patients were aged 18 years or older, and had histologically or cytologically confirmed stage IV non-squamous non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0 or 1, and received no previous chemotherapy for stage IV disease. Patients were randomly assigned (2:1; permuted block [block size of six] with an interactive voice or web response system) to receive atezolizumab (1200 mg intravenously every 3 weeks) plus chemotherapy (carboplatin [area under the curve 6 mg/mL per min every 3 weeks] plus nab-paclitaxel [100 mg/mBetween April 16, 2015, and Feb 13, 2017, 724 patients were randomly assigned and 723 were included in the intention-to-treat population (one patient died before randomisation, but was assigned to a treatment group; this patient was excluded from the intention-to-treat population) of the atezolizumab plus chemotherapy group (483 patients in the intention-to-treat population and 451 patients in the intention-to-treat wild-type population) or the chemotherapy group (240 patients in the intention-to-treat population and 228 patients in the intention-to-treat wild-type population). Median follow-up in the intention-to-treat wild-type population was similar between groups (18·5 months [IQR 15·2-23·6] in the atezolizumab plus chemotherapy group and 19·2 months [15·4-23·0] in the chemotherapy group). In the intention-to-treat wild-type population, there were significant improvements in median overall survival (18·6 months [95% CI 16·0-21·2] in the atezolizumab plus chemotherapy group and 13·9 months [12·0-18·7] in the chemotherapy group; stratified hazard ratio [HR] 0·79 [95% CI 0·64-0·98]; p=0·033) and median progression-free survival (7·0 months [95% CI 6·2-7·3] in the atezolizumab plus chemotherapy group and 5·5 months [4·4-5·9] in the chemotherapy group; stratified HR 0·64 [95% CI 0·54-0·77]; p0·0001]). The most common grade 3 or worse treatment-related adverse events were neutropenia (152 [32%] of 473 in the atezolizumab plus chemotherapy group vs 65 [28%] of 232 in the chemotherapy group), anaemia (138 [29%] vs 47 [20%]), and decreased neutrophil count (57 [12%] vs 19 [8%]). Treatment-related serious adverse events were reported in 112 (24%) of 473 patients in the atezolizumab plus chemotherapy group and 30 (13%) of 232 patients in the chemotherapy group. Treatment-related (any treatment) deaths occurred in eight (2%) of 473 patients in the atezolizumab plus chemotherapy group and one (1%) of 232 patients in the chemotherapy group.IMpower130 showed a significant and clinically meaningful improvement in overall survival and a significant improvement in progression-free survival with atezolizumab plus chemotherapy versus chemotherapy as first-line treatment of patients with stage IV non-squamous non-small-cell lung cancer and no ALK or EGFR mutations. No new safety signals were identified. This study supports the benefit of atezolizumab, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer.F. Hoffmann-La Roche.

Immune checkpoint inhibitors (ICPIs) have revolutionized the treatment paradigm of a wide range of malignancies with durable responses seen in even advanced, refractory cancers. Unfortunately, only a small proportion of patients with cancer derive meaningful benefit to ICPI therapy, and its use is also limited by significant immune and financial toxicities. Thus, there is a critical need for the development of biomarkers to reliably predict response to ICPI therapy. Only a few biomarkers are validated and approved for use with currently Food and Drug administration (FDA)-approved ICPIs. The development and broad application of biomarkers is limited by the lack of complete understanding of the complex interactions of tumor-host environment, the effect of immunotherapies on these already complex interactions, a lack of standardization and interpretation of biomarker assays across tumor types. Despite these challenges, the field of identifying predictive biomarkers is evolving at an unprecedented pace leaving the clinician responsible for identifying the patients that may derive optimal benefit from ICPIs. In this review, we provide clinicians with a current and practical update on the key, clinically relevant biomarkers of response to ICPIs. We categorize the current and emerging biomarkers of response to ICPIs in four major categories that govern anticancer response-the inflamed tumor, tumor antigens, immune suppression, and overall host environment.

Meningiomas are primary CNS tumors that arise from the arachnoid layer of the meninges. Genomic sequencing has revealed that NF2 mutations are the most common genetic alteration seen in meningiomas. Meningiomas although usually low grade, can sometimes progress to high grade. A patient who had several recurrences of meningiomas since childhood presented with recurrent headaches. Imaging showed that he had another recurrence of a meningioma. He underwent surgery for resection of the meningioma and histopathology showed NF2 mutation. He was started on everolimus and bevacizumab with good effect. Studies have shown that NF-2 mutated meningiomas have a good response to everolimus and bevacizumab with increased progression-free survival time and progression-free survival time at 6 months.

Background Chimeric antigen receptor (CAR-T) T-cell therapy is a novel immunotherapy for cancer treatment in which patients are treated with targeted, genetically-modified T-cells. Common side effects include cytokine release syndrome, neurotoxicity, hypogammaglobulinemia, and increased susceptibility to infections. Long-term infectious outcomes are poorly characterized. Methods We retrospectively examined patients who received CAR-T therapy at BIDMC & MGH from July 2016 to March 2020 and evaluated bacterial, fungal, viral, and parasitic infections at 3 months intervals to 1 year following cell infusion. The incidence, timing, and outcomes of the infectious complications were evaluated. Results In total, there were 47 patients; averaging 61.4 years of age (±12 years). Primary indications for CAR-T therapy included diffuse large b-cell lymphoma (65%) and multiple myeloma (25%), chronic lymphocytic leukemia (2%) and mantle cell lymphoma (2%). Patients had received an average 4 ± 2.9 lines of chemotherapy prior to CAR-T infusion; 19 subjects (40%) had a history of prior autologous stem cell transplant. All patients received acyclovir for antiviral prophylaxis and most received either trimethoprim-sulfamethoxazole (24/47; 51%) or atovaquone (16/47; 34%) for pneumocystis prophylaxis. In the first year, 35/47 (74.5%) of subjects experienced at least one infection with an infection rate of 84.4/10,000 person days. Median time to first infection was 59 days (range 1-338 patient days). 31/47 (66.0%) subjects had at least one bacterial infection, with pulmonary (42/113; 37.2%) sources being the most common site of infection. 13/47 (27.7%) of patients had a viral infection (predominantly respiratory viral infections) and 6/47 (12.8%) had a proven or probable fungal infection. Death attributed to infection was noted in 2 subjects (4.3%), both related to COVID-19. Baseline IgG levels were significantly lower in the group with infections (p=0.028), while white blood cell count and absolute neutrophil counts were comparable. Table 1. Baseline Demographic, Clinical Characteristics, and Outcomes of 47 Recipients of CAR-T Cell Therapy by Infection Status Notes BMI: body mass index; DLBCL: diffuse large B-cell lymphoma; CLL: chronic lymphocytic leukemia; Flu/Cy: Fludarabine/cyclophosphamide; IVIG: intravenous immunoglobulin; WBC: white blood cell count; ANC: absolute neutrophil count; ALC: absolute lymphocyte count. Table 2. Characteristics of the 113 Infections in the 35 Subjects Who Developed Infections Conclusion Infectious complications, particularly of bacterial etiology, are common in the first year following CAR-T therapy. These data may inform future prophylactic strategies in this patient population. Disclosures Matthew Frigault, MD, Arcellx (Consultant)BMS (Consultant)Iovance (Consultant)Kite (Consultant)Novartis (Consultant) Jay A. Fishman, MD, Nothing to disclose Jon Arnason, MD, BMS/Juno (Advisor or Review Panel member)Regeneron (Advisor or Review Panel member)

When the COVID-19 pandemic began, formal frameworks to collect data about affected patients were lacking. The COVID-19 and Cancer Consortium (CCC19) was formed to collect granular data on patients with cancer and COVID-19 at scale and as rapidly as possible. CCC19 has grown from five initial institutions to 125 institutions with >400 collaborators. More than 5,000 cases with complete baseline data have been accrued. Future directions include increased electronic health record integration for direct data ingestion, expansion to additional domestic and international sites, more intentional patient involvement, and granular analyses of still-unanswered questions related to cancer subtypes and treatments.

Background For cancer patients, coronavirus disease 19 (COVID‐19) infection can lead to delays in cancer therapy both due to the infection itself and due to the need to minimize exposure to other patients and to staff. Clearance guidelines have been proposed, but expected time to clearance has not been established. Methods We identified all patients at a tertiary care hospital cancer center between 25 March 2020 and 6 June 2020 with a positive nasopharyngeal reverse transcriptase polymerase chain reaction (RT‐PCR) test for the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a cancer‐related visit within 3 years, and at least one follow‐up assay. We determined the time to clearance using American Society of Clinical Oncology (ASCO), the UK National Institute for Health and Care Excellence (UK‐NICE), and Centers for Disease Control and Prevention (CDC) criteria. A matched non‐cancer comparison cohort was also identified. Results Thirty‐two cancer patients were identified. Nineteen were cleared by ASCO criteria, with estimated median time to clearance of 50 days. Fourteen patients resumed chemotherapy prior to clearance. Using UK‐NICE criteria, median time to clearance would have been 31 days, and using CDC criteria, it would have been 13 days. The matched non‐cancer cohort had similar clearance time, but with less frequent testing. Conclusion SARS‐CoV‐2 clearance times differ substantially depending on the criteria used and may be prolonged in cancer patients. This could lead to a delay in cancer care, increased use of clearance testing, and extension of infection control precautions., In this single‐institution retrospective cohort study, the median time to SARS‐CoV‐2 clearance among cancer patients was 50 days using the ASCO/CDC criteria of two negative RT‐PCR assays >24 h apart. Using alternative criteria of one negative RT‐PCR assay (UK‐NICE) or CDC clinical criteria (10 days after first positive RT‐PCR and 3 days after last symptoms), median clearance times were 31 and 13 days, respectively.

Key Points Cumulative incidence of overall thrombosis was 2.5% and of bleeding was 3.7% at day 30 after discharge for hospitalization for COVID-19. These data highlight the importance of a data-driven risk-benefit ratio assessment for postdischarge extended thromboprophylaxis., Coronavirus disease 2019 (COVID-19) is associated with a prothrombotic state with a high incidence of thrombotic events during hospitalization; however, data examining rates of thrombosis after discharge are limited. We conducted a retrospective observational cohort study of discharged patients with confirmed COVID-19 not receiving anticoagulation. The cohort included 163 patients with median time from discharge to last recorded follow-up of 30 days (interquartile range [IQR], 17-46 days). The median duration of index hospitalization was 6 days (IQR, 3-12 days) and 26% required intensive care. The cumulative incidence of thrombosis (including arterial and venous events) at day 30 following discharge was 2.5% (95% confidence interval [CI], 0.8-7.6); the cumulative incidence of venous thromboembolism alone at day 30 postdischarge was 0.6% (95% CI, 0.1-4.6). The 30-day cumulative incidence of major hemorrhage was 0.7% (95% CI, 0.1-5.1) and of clinically relevant nonmajor bleeds was 2.9% (95% CI, 1.0-9.1). We conclude that the rates of thrombosis and hemorrhage appear to be similar following hospital discharge for COVID-19, emphasizing the need for randomized data to inform recommendations for universal postdischarge thromboprophylaxis., Visual Abstract

Background Coronavirus disease-2019 (COVID-19) is a recognized prothrombotic state. Patients hospitalized with active cancer are predisposed to thrombosis but whether active cancer further amplifies thrombotic risk with COVID-19 is not known. Objectives To evaluate cumulative incidences of thrombotic and hemorrhagic events in hospitalized COVID-19 patients with and without active cancer at 28 days. Methods A retrospective cohort analysis of consecutive adults hospitalized with COVID-19 was performed. Active cancer required cancer-directed therapy within previous 6 months. The cumulative incidences of thrombosis or hemorrhage were estimated considering death as a competing risk. Results Patients without cancer (n = 353) and active cancer (n = 45) were comparable in terms of age, sex, antibiotics administered, length of hospitalization, and critical care. The most common malignancies were lymphoid (17.8%), gastrointestinal (15.6%), lung (13.3%), and genitourinary (13.3%). At day 28, the cumulative incidence of thrombotic events was 18.2% (95% confidence interval [CI], 10.2%-27.9%) in the non-cancer cohort and 14.2% (95% CI, 4.7%-28.7%) in the cancer cohort. The cumulative incidence of major and fatal bleeding at day 28 was 20.8% (95% CI, 12.1%-31.0%) in the non-cancer group and 19.5% (95% CI, 5.5%-39.8%) in the cancer cohort. Three patients experienced fatal bleeds, all of whom were in the non-cancer cohort. Survival was significantly shorter in the group with active cancer (P = .038). Conclusions We observed a similarly high incidence of thrombosis and bleeding among patients admitted with COVID-19 with or without active cancer.

Primary bone lymphoma (PBL) is a subtype of lymphoma that exclusively affects skeletal tissue. Despite the relatively common involvement of skeletal structures as a manifestation of non-Hodgkin’s lymphoma (NHL), primary and exclusive involvement of the skeletal system is rare. The prevalence of PBL is estimated to be 3–7% amongst primary bone tumors and less than 2% amongst all lymphomas in adults. However, the definition of primary bone lymphoma has been inconsistent over time. Within our institution, we identified four cases of primary bone lymphoma based on diagnostic criteria formed from the general consensus of multiple organizations, including the World Health Organization (WHO) and International Extranodal Lymphoma Study Group (IELSG). Here, we discuss the distinct characteristics amongst these cases in addition to performing a systematic review of current literature regarding this lymphoproliferative entity.

Patient: Female, 68-year-old Final Diagnosis: Chordoma Symptoms: Hoarseness • neck pain • weakness Medication: — Clinical Procedure: — Specialty: Oncology Objective: Unusual or unexpected effect of treatment Background: Chordoma is rare, but aggressive bone tumor, primarily affecting the axial skeleton. Systemic chemotherapies are not effective against the tumor, and treatment primarily consists of surgical resection and radiation. Despite these treatment modalities, recurrence is common. Our case highlights the role of afatinib as an effective treatment option in such cases. Case Report: We present case of 68-year-old female with chordoma, who underwent multiple surgical resections, radiotherapy session, and had course complication by disease progression on imatinib and local recurrence. She was eventually placed on afatinib with good effect. Conclusions: This article discusses the effectiveness of afatanib as a treatment modality, along with diagnosis, histopathological features, associated genetic aberrations, currently available and upcoming treatment options. Special emphasis is placed on molecular targeted therapy, emerging immunotherapies and use of vaccination in this field.

Background: Chronic graft versus host disease (cGVHD) remains a significant cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HCT), with a cumulative incidence of 50% (Arora et al, Biol Blood Marrow Transplant 2016). Systemic corticosteroids are considered first-line therapy, and best approach to managing steroid-refractory cGVHD is lacking. Abatacept is a recombinant fusion protein consisting of the extracellular domain of human cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) linked to the modified Fc portion of human immunoglobulin G1 (IgG1) to prevent complement fixation and antibody-dependent cellular cytotoxicity. Abatacept is a selective costimulation modulator that binds specifically to CD80 and CD86 on antigen presenting cells, thus attenuating CD28-mediated T cell activation. We previously reported results from a Phase I clinical trial evaluating the safety and clinical efficacy of abatacept in patients with steroid-refractory cGVHD (Nahas et al, Blood 2018 #NCT01954979). Here we report results of the phase II study evaluating the overall clinical response rate of abatacept in patients with steroid-refractory cGVHD. Methods: Allogeneic bone marrow or stem cell transplantation recipients were eligible if they developed cGVHD as defined by NIH consensus criteria and were treated with prednisone ≥ 0.25 mg/kg/day for at least 4 weeks without complete resolution of signs and symptoms. Peripheral blood was drawn prior to each dose of abatacept and following completion of therapy to assess the effect of treatment on circulating T cells. Abatacept was administered at 10mg/kg for a total of 6 doses. Doses 1-3 were administered at two-week intervals. One month after administration of Dose 3, abatacept was given at four-week intervals for Doses 4-6. Patients who completed 6 doses of abatacept and continued to demonstrate response were eligible to receive extended duration therapy with monthly abatacept at a dose of 10mg/kg for up to a total of 12 additional doses. Primary study endpoint was overall response rate (ORR) of using abatacept in treating cGVHD. Complete response (CR) was defined as resolution of all manifestations in each organ or site, and partial response (PR) was defined as improvement in at least one organ or site without progression in any other organ or site as per the 2014 NIH Chronic GVHD Consensus Response Criteria (Lee et al Biol Blood Marrow Transplant 2015). Results: 39 subjects with median age of 62 years (range 25-77 years) had undergone HCT a median of 43 months (range 6-173 months) prior to study entry. Patients were treated with abatacept and received a median of 8 doses (range 2-18). 17 patients had moderate cGVHD and 22 patients had severe cGVHD at baseline. Baseline cGVHD assessment of the 39 evaluable patients showed involvement of the skin in 85% (n=33), mouth in 44% (n=17), eyes in 69% (n=27), gastrointestinal tract (GI) in 18% (n=7), liver in 23% (n=9), lung in 54% (n=21), joints in 82% (n=32), and genital tract in 8% (n=3). The ORR was 49% (19/39 patients) with CR 0% and PR 49%. The organ sites with greatest improvement included lung (33%), eyes (23%), mouth (21%), and joints (21%). Progression of disease occurred in 26% of patients (n=10), with sites of involvement including skin (8%), mouth (10%), eyes (5%), lung (3%), and joints (5%). Baseline median daily dose of prednisone was 20mg with a 27.5% reduction at 1-month follow-up to 14.5mg (p Conclusions: Abatacept is associated with a 49% ORR in steroid refractory cGVHD and leads to durable reduction in prednisone dosing over time. Severe infections are uncommon and the infusions are well tolerated. Abatacept represents a promising novel therapeutic agent for patients with steroid-refractory cGVHD. Disclosures Stroopinsky: The Blackstone Group: Consultancy. Arnason: Juno/BMS: Honoraria. Cutler: Cimeio: Consultancy; Editas: Consultancy; Kadmon: Consultancy; Pfizer: Consultancy; Mallinckrodt: Consultancy; CareDx: Consultancy; Incyte: Consultancy; Omeros: Consultancy; Syndax: Consultancy; Mesoblast: Consultancy; Deciphera: Consultancy; Jazz: Consultancy. Nikiforow: Kite/Gilead: Other: ad HOC Advisory Boards; Novartis: Other: ad Hoc Advisory Boards; Iovance: Other: ad Hoc Advisory Boards; Glaxo Smith Kline (GSK): Other: ad Hoc Advisory Boards. Avigan: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Kite Pharma: Consultancy, Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Partner Tx: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Aviv MedTech Ltd: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; Chugai: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Parexcel: Consultancy; Takeda: Consultancy; Sanofi: Consultancy. Soiffer: Rheos Therapeutics, USA: Consultancy; Kiadis, Netherlands: Membership on an entity's Board of Directors or advisory committees; Juno Therapeutics, USA: Other: Data Safety Monitoring Board; Precision Biosciences, USA: Consultancy; Jazz Pharmaceuticals, USA: Consultancy; Takeda: Consultancy; Jasper: Consultancy; Gilead, USA: Other: Career Development Award Committee; NMPD - Be the Match, USA: Membership on an entity's Board of Directors or advisory committees. Rosenblatt: Attivare Therapeutics: Consultancy; Parexel: Consultancy; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Imaging Endpoints: Consultancy; Wolters Kluwer Health: Consultancy, Patents & Royalties; Bristol-Myers Squibb: Research Funding.

Introduction: Immunotherapy for AML holds promise in overcoming chemotherapy resistance and in preserving immunologic memory necessary for durable remissions.A bispecific T-cell engaging antibody targeting CD3 and CD123 (CD123-CODV-TCE) has been shown to stimulate T cells to target CD123-expressing leukemic cells in vitroand in mouse models 1. While the short-term immune stimulation mediated by the CD123TCE has the potential to result in clinical response, long-term disease control will require the development of immune memory. We have developed a personalized cancer vaccine in which patient's dendritic cells are fused with autologous leukemia cells resulting in presentation of a wide range of antigens to the immune system. Here, we describe a novel combination of CD123TCE with a DC/AML fusion vaccine ex vivo and in a xenograft murine model. We hypothesized that the CD123TCE will direct the vaccine-educated T cells to not only more effectively eradicate target leukemia cells but also evoke a repertoire of memory T cells and long-term response. Methods/Results: AML cells expressing CD123 were isolated from bone marrow mononuclear cells (BMMCs) from AML patients (n=3). DCs were generated from autologous adherent peripheral blood mononuclear cells (PBMCs) obtained at the time of disease remission as previously described 2,3. Concurrently, CD3+ T cells were isolated from the non-adherent fraction of PBMCs using magnetic bead separation. Fusion cells were generated by co-culturing the DC and tumor cells at a ratio of 3:1 in the presence of polyethylene glycol (PEG). Vaccine educated T cells were then generated by co-culture of T cells with the autologous fusion cells at a ratio of 10:1 for 5-7 days followed by T cell expansion via CD3/CD28 ligation. The capacity of the vaccine-educated T cells to target autologous leukemia cells with the addition of CD123TCE was assessed. The results demonstrated a statistically significant increase in Granzyme B activity in the target AML cells following co-culture with vaccine-educated T cells and the addition of the CD123TCE, compared to T cells + isotype control (n=3). Furthermore, vaccine stimulation in combination with CD123TCE led to a robust increase in induction of tumor specific activated T cells as detected by CD137 expression and intracellular IFN-γ production after co-culture of vaccine-educated T cells with autologous tumor cells in the presence of CD123TCE. The addition of CD123TCE to vaccine-educated T cells resulted in mean 25.4% and 9.6% intracellular IFN-γ expression for CD8 and CD4 T cells, respectively, compared to 8.5 and 3.1% IFN-γ expression following the addition of isotype control (n=3). Next, we examined the efficacy of the combined treatment with vaccine-educated T cells and CD123TCE in-vivo, in two independent xenograft experiments. NSG mice were irradiated with 300rads and challenged with 1x10 6 patient-derived CD123+ tumor cells via retro-orbital injections. After detection of human AML engraftment in the PB on day 76, the mice were inoculated IV with 1X10 6 resting, or ex vivo fusion vaccine educated autologous T cells IV. Subsequently, cohorts of mice were treated with CD123TCE or an appropriate isotype control every 3 days IP. A significant decrease in human leukemia burden was detected in the peripheral blood, spleen and bone marrows of analyzed animals after treatment with vaccine educated T cells and isotype control, or resting T cells and CD123TCE, compared to untreated mice (n=5). Strikingly, no detectable AML was found in peripheral blood, spleens and bone marrows of mice treated with vaccine educated T cells in combination with TCE (n=5). Of note, treatment with vaccine educated T cells led to an expansion of human CD3+ T cells in tissues obtained from the analyzed animals. These human T cells persisted in mice treated with the CD123TCE with a two-fold increase in tumor-specific CD8+ T cells, as assessed by intracellular IFN-γ secretion following ex vivo stimulation with autologous tumor lysate. Conclusions: We demonstrated that the combination of DC/AML fusion vaccine and CD123TCE led to increase in tumor specific T cell immunity, both ex-vivo and in a xenograft murine model when compared to uneducated T cells with CD123TCE or educated T cells with isotype control molecule. Most significantly, the combination treatment was shown to eradicate AML in this model with all animals remaining disease-free several months post inoculation. Disclosures Stroopinsky: The Blackstone Group: Consultancy. Nahas: Kite Pharma: Current Employment. Fraenkel: Sanofi: Current Employment. Yildirim: Sanofi: Current Employment. Bonnevaux: Sanofi: Current Employment. Guerif: Sanofi: Current Employment. Kufe: Genus Oncology: Current equity holder in publicly-traded company; Canbas: Consultancy; REATA: Consultancy, Current equity holder in publicly-traded company; Hillstream BioPharma: Current equity holder in publicly-traded company. Rosenblatt: Parexel: Consultancy; Wolters Kluwer Health: Consultancy, Patents & Royalties; Bristol-Myers Squibb: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Imaging Endpoints: Consultancy; Attivare Therapeutics: Consultancy. Avigan: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Kite Pharma: Consultancy, Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Partner Tx: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Aviv MedTech Ltd: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; Chugai: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Parexcel: Consultancy; Takeda: Consultancy; Sanofi: Consultancy.

Allogeneic transplantation is uniquely curative for a subset of patients with acute myeloid leukemia (AML) however, post-transplant relapse and graft versus host disease remain significant concerns. We have developed a vaccine in which patient-derived AML cells are fused with donor-derived dendritic cells (DCs), thereby presenting a broad array of antigens. Previous work (Rosenblatt Sci Transl Med) has suggested that such vaccines given in the first complete remission setting after chemotherapy consolidation elicit specific immune responses and can possibly lessen the risk of relapse. We hypothesize that donor-derived DC/AML vaccination post-transplant would elicit the durable expansion of leukemia- specific T cells within the donor T cell repertoire to effectively protect against disease relapse. We report the results of a phase 1 clinical trial (NCT03679650) evaluating the use of DC/AML fusion vaccine in patients with acute myeloid leukemia (AML) following allogeneic transplant. DC/AML fusion vaccine is generated with autologous leukemia blasts, cryopreserved at the time of diagnosis with AML, and donor-derived dendritic cells. DCs are collected via leukapheresis in pts in CR 25-70 days after an allogenic matched related or unrelated donor transplant (cohort A) or a haplo-identical donor (Cohort B). In order to proceed with leukapheresis, patients must demonstrate donor hematopoietic recovery and the absence of ongoing grade 2 or higher GVHD. For DC generation, donor-derived adherent mononuclear cells are cultured with GM-CSF, IL-4 and TNFa. Vaccine is administered subcutaneously starting day 70-100 post-transplant. 2 vaccines are given at 3 week intervals, in conjunction with 100 mcg GMCSF daily at the vaccine site for 4 days. A booster vaccine is given 30-60 days following the taper of immune suppression, in the absence of GVHD. Profiling of the immune microenvironment using single cell RNA sequencing from samples obtained before and after vaccination is being carried out. 17 participants have been enrolled. The median age was 59 years (range 23-74). 15 patients were enrolled to cohort A: 8 were transplanted with a matched unrelated donor and 7 were transplanted with a matched sibling donor. 2 participants were enrolled to cohort B. The median yield of leukemia cells was 207x10 6 (range 80-818x10 6)and mean viability was 96.5%. The median yield of DCs was 133x10 6 (range 29-182x10 6) and mean viability 72%. Fusion vaccine was successfully generated in 14/16 patients. One patient had insufficient DC, one patient relapsed prior to leukapheresis and one vaccine is currently in process. Mean fusion efficiency was 52% with viability of 78.6%. Mean fusion vaccine dose was 4.36 x10 6 cells. 3 patients from whom vaccine was generated did not meet eligibility to initiate vaccination due to ongoing toxicity following transplant or GVHD. 11 participants have initiated vaccine administration and are evaluable for toxicity and response. The most common side effects have been vaccine site reactions (n=10 grade 1, n=2 grade 2). 7 patients developed GVHD that was determined to be possibly related to vaccination, at a median time of 19 days after vaccination (range 5-70 days). 2 of these patients developed grade 2 acute GVHD of the skin, and 5 developed chronic GVHD affecting one to up to four organ systems ranging from mild to severe. There were 5 additional GVHD events with a median time of 115 days post vaccination (range 91-126 days), assessed as unlikely related or unrelated to vaccine based on timing of onset. 10 of 11 evaluable patients remain in a CR at a median time of 21 months post-transplant (range 6-33 months). One patient died of relapsed disease 15 months post transplant and another died of GVHD and infection unrelated to vaccine 21 months post transplant. Vaccination using patient-derived autologous leukemia cells and donor derived DC isolated following engraftment of hematopoietic cells appears safe and feasible. Toxicity of vaccination has included injection site reactions as well as graft versus host disease, primarily mild to moderate severity. Outcomes to date demonstrate that vaccination post-transplant may be a promising strategy to reduce relapse as 10 of 11 vaccinated patients remain relapse free. However this approach is limited to patients who have not had early relapse or early GVHD post-transplant. Immune correlates, including single cell RNA sequencing of the immune milieu, are ongoing. Disclosures Stone: Abbvie: Consultancy; Actinium: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Aprea: Consultancy; Arog: Consultancy, Research Funding; Astellas: Membership on an entity's Board of Directors or advisory committees; BerGen Bio: Membership on an entity's Board of Directors or advisory committees; Boston Pharmaceuticals: Consultancy; Bristol Meyers Squibb: Consultancy; Celgene: Consultancy; Elevate Bio: Membership on an entity's Board of Directors or advisory committees; Foghorn Therapeutics: Consultancy; Gemoab: Membership on an entity's Board of Directors or advisory committees; Glaxo Smith Kline: Consultancy; Innate: Consultancy; Janssen: Consultancy; Jazz: Consultancy; Macrogenics: Consultancy; Novartis: Consultancy, Research Funding; OncoNova: Consultancy; Syndax: Membership on an entity's Board of Directors or advisory committees; Syntrix/ACI: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy. Soiffer: Takeda: Consultancy; Jasper: Consultancy; Jazz Pharmaceuticals, USA: Consultancy; Precision Biosciences, USA: Consultancy; Juno Therapeutics, USA: Other: Data Safety Monitoring Board; Kiadis, Netherlands: Membership on an entity's Board of Directors or advisory committees; Rheos Therapeutics, USA: Consultancy; Gilead, USA: Other: Career Development Award Committee; NMPD - Be the Match, USA: Membership on an entity's Board of Directors or advisory committees. Stroopinsky: The Blackstone Group: Consultancy. Romee: Glycostem: Membership on an entity's Board of Directors or advisory committees; Crispr Therapeutics: Research Funding. Neuberg: Madrigal Pharmaceuticals: Other: Stock ownership; Pharmacyclics: Research Funding. Kufe: Canbas: Consultancy; Hillstream BioPharma: Current equity holder in publicly-traded company; Genus Oncology: Current equity holder in publicly-traded company; REATA: Consultancy, Current equity holder in publicly-traded company. Avigan: Chugai: Membership on an entity's Board of Directors or advisory committees; Partner Tx: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Parexcel: Consultancy; Janssen: Consultancy; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Juno: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Sanofi: Consultancy; Aviv MedTech Ltd: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Rosenblatt: Wolters Kluwer Health: Consultancy, Patents & Royalties; Parexel: Consultancy; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Imaging Endpoints: Consultancy; Bristol-Myers Squibb: Research Funding; Attivare Therapeutics: Consultancy.

Background: In Zuma-1 study, approximately 40% of patients with refractory or relapsed large B cell lymphoma (LBCL) show durable response to Axi-cel. The identification of immunologic factors predictive of therapeutic efficacy and tumor escape is a critical area of investigation. The impact of CAR T cell activation on the native T cell repertoire and lymphoma specific immunity has not been elucidated. Aim: We sought to determine the role of host immune activation in response to tumor-associated antigens and the impact of consequent epitope spreading on CAR-T mediated therapeutic efficacy. To this end, we performed longitudinal single cell immunoprofiling of peripheral blood samples from ZUMA-1 patients to capture immune cell subsets and T cell repertoire during axi-cel treatment. Methods: Single cell immunoprofiling (expression + V(D)J sequencing) was performed on PBMC samples from ZUMA-1 patients (N=32), collected at leukapheresis, 4 weeks, and 6 months post CAR-T cell infusion, to examine potential markers associated with response and resistance. scRNA-seq was performed using 10x Genomics Chromium Next GEM Single Cell 5' Kit v1.1. Full-length paired α/β TCR and BCR libraries were obtained using the Chromium Single Cell V(D)J Enrichment, Human T Cell/B cell kits following manufacturer instructions, while γ/δ TCR libraries were generated using custom primers. Results: Analysis has been completed on the pilot implementation comprising 3 patients. A total of 22,403 cells passed quality-check capturing 31 cellular populations (Figure 1a). In 2 of the 3 patients analyzed, CD8 T cells, after an initial decrease at 4 weeks post CAR T infusion, exhibited an increase at 6 months post CAR T infusion reaching higher levels than those observed prior to CAR T treatment. The third patient presented an increase of the CD8 T cell compartment at 4 weeks compared to pretreatment (Figure 1a). A similar trend was observed for CD4 T cell population, with an increase at 6 months post CAR-T to a level higher than prior to CAR T infusion (Figure 1a). On the contrary, the myeloid cell compartment depicted a gradual decrease from leukapheresis to 6 months post CAR T (Figure 1a). B cells were observed only in 1 of the 3 patients at 6 months (Figure 1a). α/β TCR, γ/δ TCR and BCR clonotypes were identified and projected on the 2-dimensional embedding (Figure 1b). Full-length paired α/β TCR at single cell level showed that some of the most abundant clonotypes at baseline continued to be prominent in post CAR T timepoints (Figure 1c). An extensive expansion of new clonotypes was observed at 6 months after infusion. Moreover, in 2 of the 3 patients, we observed that T cell clonal diversity converged at 4 weeks, and diverged in one patient at 6 months post treatment (Figure 1d). The analysis of the remaining 29 patients (87 samples) is ongoing. Conclusion: The application of single cell immunoprofiling on longitudinal samples from Axi-cel-treated LBCL patients successfully captured the changes in the cellular transcriptional landscape, cell proportions, and TCR/BCR space across the time axis in high resolution. It is anticipated that the full analysis of 32 patients can elucidate the transcriptional program in response to CAR T cell therapy. Figure 1: (A) Two-dimensional uniform manifold approximation and projection (UMAP) of all cells passing QC (n=22,403), separated per patient and timepoint. (B) T and B cell receptor clonality at single cell resolution. T and B cells with one or more clones are colored. (C) α/β clonotype frequency per timepoint for each patient. (D) T Cell receptor Shannon diversity index per timepoint for the 3 profiled patients. Dashed lines connect the different timepoints from the same patient. Figure 1 Figure 1. Disclosures Stroopinsky: The Blackstone Group: Consultancy. Bot: Kite, a Gilead Company: Current Employment; Gilead Sciences: Consultancy, Current equity holder in publicly-traded company, Other: Travel support. Mattie: Kite: Current Employment. Chou: Kite Pharma: Current Employment. Rosenblatt: Karyopharm: Membership on an entity's Board of Directors or advisory committees; Parexel: Consultancy; Wolters Kluwer Health: Consultancy, Patents & Royalties; Bristol-Myers Squibb: Research Funding; Imaging Endpoints: Consultancy; Attivare Therapeutics: Consultancy. Avigan: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Kite Pharma: Consultancy, Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Partner Tx: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Aviv MedTech Ltd: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; Chugai: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Parexcel: Consultancy; Takeda: Consultancy; Sanofi: Consultancy.

Background: CAR-T cells are a tremendous breakthrough in the treatment of certain type of blood cancer, demonstrating impressive and durable responses. However, mechanisms of resistance and relapse have been reported. Mechanisms contributing to relapse after CAR-T therapy include the downregulation of the CAR-T target antigen and the rapid extinguishing of CAR-T cells. We have developed a personalized cancer vaccine whereby patient derived tumor cells are fused to autologous dendritic cells (DC). DC/tumor vaccine induces a broad anti-tumor immunity capable of preventing relapse but may not be effective in patients with advanced disease. Aims: We sought to overcome relapse and resistance to CAR-T therapy to improve the current response rate to CAR-T cells. To this end, we combined CAR-T cells treatment with our personalized DC/tumor vaccine. We postulated that the DC/tumor vaccine would demonstrate synergy with CAR-T cells in a setting where CAR-T cells reduce the bulky disease and the fusion vaccine prevents relapse by expanding CAR-T cells and tumor antigen specific lymphocytes. Methods: To investigate the effects of the CAR-T/fusion vaccine combination, we used the A20 murine B-cell lymphoma model. Syngeneic T cells were obtained from BALB/c mice and retrovirally transduced with a second-generation CAR construct composed of an antigen binding domain that recognizes murine CD19, the CD3ζ domain, 4-1BB as costimulatory molecule and GFP (m19BBz-GFP). GFP expression was used to assess gene-transfer efficiency and monitor the CAR-transduced T cells. The DC/tumor vaccine was obtained by PEG-mediated fusions of A20 cells and BALB/c DC. In the in vitro experiments, T cells transduced with the m19BBz-GFP CAR or non-transduced T cells were co-cultured in the presence or the absence of the DC/A20 vaccine for 3 days. Tumor killing was measured by quantifying Firefly luciferase activity (WT A20) or Renilla luciferase activity (CD19- A20). Vaccine was removed before starting the killing assay. In the in vivo experiment, B-cell lymphoma was induced in BALB/c mice by tail vein injection of A20 cells. The mice were lymphodepleted and treated with m19BBz-GFP CAR-T. The mice were then subcutaneous injected with the DC/A20 fusion vaccine or with PBS (control group). CD8+ T-cells specific for the A20 idiotype epitope were quantified by MHC Class I tetramer analysis. Results: In vitro co-culture of CAR-T cells and DC/A20 vaccine induced a memory-like CAR-T phenotype and strongly improved CAR-T persistence (measured as % of GFP+ T cells in culture). These results were confirmed in vivo where increased CAR-T percentage was observed in the bone marrow and spleen of vaccinated mice with respect to the unvaccinated control group. Moreover, in the vaccinated mice we detected CD8+ T-cells specific for the A20 idiotype epitope demonstrating the expansion of tumor-specific lymphocytes in response to the fusion vaccine. To assess whether the vaccine-induced persistence of CAR-T cells was translated in a higher tumor killing capacity, we performed an in vitro killing assay. To mimic the presence of CD19- clones in the tumor bulk, we used a mixture of WT A20 and CD19-A20 as CAR-T target cells. Enhanced killing capacity against CD19+ tumors was induced by education of the CAR-T with the vaccine. No effects on the CAR-T killing capacity against CD19- A20 were elicited by the fusion vaccine. However, when the same killing assay was performed using as effector cells a mixture of CAR-T and naïve T cells or a mixture of CAR-T and vaccine-educated T cells, we observed that the addition of vaccine-educated T cell to the CAR-T, strongly reduced both A20 WT and A20 CD19- in the cultures. Thus, vaccine-educated T cells are able to kill tumor cells independently from the presence or the absence of the CAR-T target antigen on the tumor. Conclusions: The combination of CAR-T and DC/tumor vaccine, increasing the persistence of CAR-T cells and evoking a polyclonal T cell response against tumor antigens in the non-CAR-transduced T cells, may represent a novel therapeutic strategy to overcame therapeutic resistance and improve current response rate to CAR-T therapy. Disclosures Capelletti: Caris Life Sciences: Current Employment. Stroopinsky: The Blackstone Group: Consultancy. Kufe: REATA: Consultancy, Current equity holder in publicly-traded company; Genus Oncology: Current equity holder in publicly-traded company; Hillstream BioPharma: Current equity holder in publicly-traded company; Canbas: Consultancy. Themeli: Fate Therapeutics: Patents & Royalties. Rosenblatt: Attivare Therapeutics: Consultancy; Imaging Endpoints: Consultancy; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Parexel: Consultancy; Wolters Kluwer Health: Consultancy, Patents & Royalties; Bristol-Myers Squibb: Research Funding. Sadelain: Minerva Biotechnologies: Patents & Royalties; Juno Therapeutics: Patents & Royalties; Fate Therapeutics: Other: Provision of Services (uncompensated), Patents & Royalties; Mnemo Therapeutics: Patents & Royalties; Takeda Pharmaceuticals: Other: Provision of Services, Patents & Royalties; Ceramedix: Patents & Royalties; NHLBI Gene Therapy Resource Program: Other: Provision of Services (uncompensated); St. Jude Children's Research Hospital: Other: Provision of Services; Atara Biotherapeutics: Patents & Royalties. Avigan: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Kite Pharma: Consultancy, Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Partner Tx: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Aviv MedTech Ltd: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; Chugai: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Parexcel: Consultancy; Takeda: Consultancy; Sanofi: Consultancy.

Nearly all men with prostate cancer who are treated with androgen deprivation therapy develop disease progression. There is considerable evidence to suggest that CXCL 13 released by tumor cells leads to B-cell infiltration into the prostate cells. This B-cell infiltration has been postulated to play a role in development of disease progression following androgen-deprivation therapies. We present a case of a patient who achieved remission of metastatic castrate-resistant prostate cancer after receiving rituximab and bendamustine for the treatment of follicular lymphoma. The findings in this report suggest that further investigation is warranted for utilizing B-cell targeted therapy in delaying progression of castrate-resistant prostate cancer.

Background DICER1 syndrome is an autosomal dominant tumour predisposition syndrome associated with a wide variety of cancerous and noncancerous conditions, including ovarian sex cord–stromal tumours and thyroid conditions, including multinodular goiter. The most common ovarian sex cord–stromal tumour associated with DICER1 syndrome is Sertoli–Leydig cell tumour, with germline DICER1 mutations present in more than 50% of cases. We present a case in which a patient in her late 30s was diagnosed with a Sertoli–Leydig cell tumour in the background of a strong family history of multinodular goiter and Sertoli–Leydig cell tumour with a germline mutation in DICER1. Case Presentation A 38-year-old woman with history of multinodular goiter was found to have stage iiic ovarian Sertoli–Leydig cell cancer after presenting with abdominal pain. She underwent multiple surgeries and chemotherapy. The patient developed rapid disease progression and died 7 months after diagnosis. Seven years earlier, a daughter had experienced the same disease and was found to have a germline DICER1 mutation. The mother had not undergone testing before her own diagnosis. Summary The co-occurrence of Sertoli–Leydig cell tumour and multinodular goiter is highly suggestive of DICER1 syndrome. The recognition of DICER1 syndrome within a family is essential for increased awareness and potential early recognition of complications. Most conditions associated with DICER1 syndrome occur in childhood, and most of the current screening recommendations are specific for childhood and young adulthood. Cancer risks and findings for the adult population are not as well defined. Clinicians who encounter DICER1 syndrome should review recommendations for genetic testing and surveillance and enrol patients in the DICER1 registry.

Immune checkpoint inhibitors have ushered in a new era in cancer management. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that selectively inhibits programmed cell death-1 (PD-1) activity by binding to the PD-1 receptor. This inhibits suppression of the T-cell activity, which can in turn cause increased killing of cancer cells. This alteration in the activity of the T cells can cause them to lose their ability to identify host cells and leads to immune-related adverse effects (irAE). Nivolumab-induced hepatotoxicity is rare and accounts for 3–6% of all irAE. We present a case of nivolumab-induced hepatitis. A woman who was treated for recurrent renal cell carcinoma presented with hepatitis. Workup for other causes was negative and the hepatitis was attributed to the administration of nivolumab. She was started on oral steroids followed which she initially improved. However, she later presented with massive upper gastrointestinal bleeding secondary to gastroduodenal ulcers and subsequently developed acute tubular necrosis and passed from the complications. Immune checkpoint inhibitors have proven to be a promising approach in the management of a wide array of neoplasms by immunomodulation. As these agents are becoming standard of therapy in the management of cancers, a heightened vigilance in the diagnosis of irAE is warranted. With heightened vigilance, early recognition can lead to decreased mortality and morbidity.

Non-small cell lung adenocarcinoma is the most common type of lung cancer but is often difficult to treat. New treatment options have emerged with the class of tyrosine kinase inhibitors, but it has been found that certain genetic mutations in the epidermal growth factor receptor (EGFR) receptor are not as sensitive to this treatment as others. We present a case of a 78-year-old man who was diagnosed with stage IV non-small cell lung adenocarcinoma with an EGFR exon 20 mutations treated with pemetrexed, nivolumab, and then docetaxel. He has lived over four years after his initial diagnosis. This case illustrates the importance of genetic testing of patients to evaluate for specific gene mutations. It highlights the fact that these patients with exon 20 mutations are not sensitive to tyrosine kinase inhibitor treatment and often respond better to chemotherapeutic agents.

11028 Background: Evidence shows that cancer patients are interested in learning about medicinal cannabis and frequently ask their oncologists for recommendations. To determine whether oncology training is adequately preparing physicians to address this topic, we conducted a national survey of oncology trainees to determine attitudes, practices, and knowledge about medical cannabis in cancer care. Methods: An interdisciplinary team developed an electronic questionnaire assessing trainees’ current practices regarding cannabis recommendations in cancer care and their knowledge of its effectiveness and risks compared with conventional care for cancer-related symptoms. We contacted 155 oncology training programs throughout the U.S. and asked that they distribute the survey to their trainees. Primary outcomes were: whether trainees reported discussing or recommending cannabis with/to patients and whether they felt sufficiently informed to make such recommendations. We presented data as proportions and used chi-square tests to compare proportions between groups. Results: Forty training programs from 25 states participated; of the 462 trainees in these programs, 187 completed surveys, yielding a response rate of 40%. Of the participants, 52% were female, 53% White, 33% Asian, and 5% Hispanic. One third (34%) graduated medical school before 2015, and 22% attended medical school outside the US. While 24% of trainees reported having received training regarding medical cannabis, only 12% felt sufficiently informed to make cannabis recommendations. Despite this, 91% reported having discussed cannabis with patients, and 58% reported recommending cannabis clinically to more than five patients in the prior year. Many viewed it as useful adjunctive therapy that was at least as effective as conventional treatments for: anorexia/cachexia (72%), nausea/vomiting (45%), and pain (41%). Over half (55%) believed that cannabis was beneficial to patients at the end of life; 31%, patients in active treatment; 11%, cancer survivors; 20%, the elderly with cancer and 16%, young adults with cancer. Peer-reviewed material (30%), lectures or webinars by another physician (29%), and patients and their families (22%) were the most commonly cited sources of information regarding medical cannabis. Oncologists who reported at least one area of focus as supportive/palliative care were more likely to feel sufficiently informed to make recommendations than oncologists without this focus (17% vs. 4%, P = 0.01); no other demographic or practice characteristics were associated with feeling sufficiently informed (all P > 0.10). Conclusions: Although most oncology trainees discuss cannabis use with their patients, the majority do not feel sufficiently informed about its use in cancer care. This represents an unmet need in contemporary oncology training, trainee satisfaction, and patient care.

Introduction: We are conducting a clinical trial in which patients with acute myeloid leukemia (AML) who are undergoing allogeneic transplant undergo post-transplant vaccination with DC/AML fusion cells. Allogeneic transplantation is uniquely curative for a subset of patients with AML, however, post-transplant relapse and graft versus host disease remain significant concerns. We have developed a promising leukemia vaccine in which patient derived AML cells are fused with donor-derived dendritic cells (DCs), presenting a broad array of antigens that capture the heterogeneity of the leukemia cell population. We hypothesize that DC/AML vaccination post-transplant would elicit the durable expansion of leukemia specific T cells within the donor T cell repertoire to effectively protect against disease relapse. Methods: Patients undergo collection and cryopreservation of leukemia cells at the time of diagnosis with AML. Patients who undergo an allogeneic transplant in complete remission from a matched related or unrelated donor (cohort A) or a haplo-identical donor (Cohort B) are assessed for eligibility to undergo leukapheresis for dendritic cell generation between day 25-45 post-transplant. In order to proceed with leukapheresis, patients must demonstrate donor hematopoietic recovery in the absence of ongoing grade 2 or higher GVHD. Patients initiate vaccination between day 70-100 post-transplant. 2 vaccines are given at 3 week intervals, in conjunction with GMCSF 100 mcg daily at the vaccine site for 4 days. A booster vaccine may be given 30-60 days following the taper of immune suppression, in the absence of GVHD. Results: To date, 12 participants have undergone vaccine generation. The median age is 62 years (range 23-74). 10 participants were enrolled to cohort A: 7 were transplanted with a matched unrelated donor and 3 were transplanted with a matched sibling donor. 2 participants were enrolled to cohort B following transplant from a haplo-identical donor. The mean yield of leukemia cells was 314 x106 (range 95-to 818-x106)and mean viability was 96%. For DC generation, patients underwent leukapharesis and adherent mononuclear cells were cultured with GM-CSF, IL-4 and TNFa. The mean yield of DCs was 131 x106 and viability 77%. Fusion vaccine was successfully generated in 11/12 patients, with mean fusion efficiency of 51% with viability of 76%. One patient had insufficient DC for vaccine generation. Mean Fusion Vaccine Dose was 4.7 x 106 fusion cells. 3 patients did not meet eligibility to initiate vaccination due to ongoing toxicity following transplant (2 patients) and GVHD (1 patient). 8 participants have initiated vaccine administration and are evaluable for toxicity and response. The most common side effects have been grade 1 vaccine site reactions (n=9 grade 1, n=1 grade 2). 4 patients developed GVHD that was determined to be possibly related to vaccination, at a median time of 16.5 days after vaccination (range 5-21 days). 2 of these patients developed grade 2 acute GVHD of the skin, one patient developed grade 2 gastrointestinal GVHD that subsequently evolved into moderate, chronic GVHD affecting the skin, GI tract, eyes and mouth, and one patient developed mild transaminitis attributed to liver GVHD. An additional 3 patients developed GVHD with a median time of 99 days post vaccination (range 91-123 days), assessed as being unlikely related to vaccine. 7 of the 8 patients remain in a CR at a median time of 15.5 months post-transplant (range 4.8-22.4 months). One patient relapsed 14.8 months post haplo-identical transplant. Immunologic response following vaccination is being assessed, with respect to the presence of leukemia-reactive T cells, T cells targeting previously identified leukemia- associated antigens, T cell clonality, T regulatory cells, and PD-1 expressing T cells. In the absence of treatment associated toxicity, a second cohort is planned, in which vaccine will be given in conjunction with decitabine. Conclusions: Vaccine generation using donor derived DC isolated following engraftment is feasible. Mild to moderate graft versus host disease has been observed in a subset of patients, and 7/8 vaccinated patients remain relapse free. Correlative science studies to assess immune response to vaccination, identify neoantigen targets, and characterize the immune milieu, will be reported. Disclosures Stone: Syros: Consultancy; Syntrix: Consultancy; Syndax: Consultancy; Stemline: Consultancy; Hoffman LaRoche: Consultancy; Macrogenics: Consultancy; Janssen: Consultancy; Gemoab: Consultancy; Elevate: Consultancy; Daiichi-Sankyo: Consultancy; Takeda: Consultancy; Trovagene: Consultancy; Pfizer: Consultancy; Otsuka: Consultancy; Novartis: Consultancy, Research Funding; Jazz: Consultancy; Celgene: Consultancy, Other: Data and safety monitoring board; Biolinerx: Consultancy; AstraZeneca: Consultancy; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Arog: Research Funding; Argenx: Consultancy, Other: Data and safety monitoring board; Agios: Consultancy, Research Funding; Actinium: Consultancy; AbbVie: Consultancy, Research Funding. Soiffer:Gilead: Consultancy; Rheos Therapeutics: Consultancy; Cugene: Consultancy; Precision Bioscience: Consultancy; Mana Therapeutics: Consultancy; VOR Biopharma: Consultancy; Novartis: Consultancy; Juno: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; alexion: Consultancy; Be the Match/ National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Kiadis: Membership on an entity's Board of Directors or advisory committees. Neuberg:Pharmacyclics: Research Funding; Celgene: Research Funding; Madrigak Pharmaceuticals: Current equity holder in publicly-traded company.

49 Background: COVID-19 in oncologic patients presents a clinical dilemma. To reduce the risk of adverse events as well as the risk of exposing others, many institutions have established protocols to define COVID-19 clearance. However, the optimal criteria for discontinuing infection precautions and/or resuming anticancer therapy in COVID-19 patients is unknown. Methods: We identified patients with a positive COVID-19 PCR at a tertiary care hospital between 3/25/2020 and 6/6/2020, and who also had seen an oncologist for a cancer-related diagnosis within the last 3 years. COVID-19 PCR testing was performed using the Abbott Laboratories m2000 platform in conjunction with either the Aldatu Biosciences PANDAA qDxTM SARS-CoV-2 or Abbott RealTime SARS-CoV-2 assays. At our institution, and per current ASCO guidelines, discontinuation of COVID-19 precautions requires two consecutive negative viral PCR tests > 24 hours apart. Results: During the follow-up period, we identified 32 patients with a positive COVID-19 PCR who were receiving active oncology care. Half of this cohort (16/32) had metastatic disease at the time of COVID-19 diagnosis. 17 patients were on active treatment at time of COVID-19 diagnosis (8 receiving cytotoxic chemotherapy). Among patients who met criteria for COVID-19 PCR clearance, median time to clearance was 37 days (range, 10-58 days). When accounting for censoring at the time of last COVID-19 assay, median time to clearance for all patients was estimated at 50 days. 14 patients resumed anti-cancer treatment prior to COVID-19 clearance (5 received cytotoxic chemotherapy), requiring substantial allocation of staff and resources for safe treatment isolated from other oncology patients. Among the 13 patients who met clearance criteria, 2 subsequently had a positive COVID-19 PCR after resumption of treatment. We explored COVID-19 clearance time under an alternative symptom/time based strategy based on CDC criteria (at least 10 days after first positive PCR and 3 days after last day of symptoms). Under this strategy, median time to COVID-19 clearance would be 14 days. Conclusions: In patients with cancer who develop COVID-19 infection, viral shedding can persist for many weeks after disease onset, but the implications of this shedding on likelihood of infection is unknown. Treatment of COVID-19 positive oncology patients requires substantial planning and resources. Test-based versus symptom/time-based strategies for determining discontinuation of precautions and resumption of treatment should be further investigated to provide safe and effective care.

e21579 Background: P and P+C are standard-of-care (SOC) treatment options for advanced NSCLC. However, they have not yet been directly compared in clinical trials. Methods: We conducted a retrospective cohort study of patients with advanced NSCLC who initiated treatment with SOC P±C at our center from 2/11/16 to 10/15/19 (data cutoff 1/15/20). Patient demographic, clinicopathologic, therapeutic and outcomes data were extracted. All radiographic scans were independently evaluated by a thoracic radiologist using iRECIST. Survival time was defined from the start of P±C. Kaplan-Meier and Cox proportional hazards model were utilized. Results: Of 103 patients with median follow up of 17.7 months, 74 (71.8%) had received P, while 29 (28.2%) had received P+C. In PD-L1 tumor proportion score (TPS) unselected population, there were no significant differences in age, sex, smoking status, driver mutation, tumor mutational burden (TMB), line of therapy, ECOG performance status (PS) or immune-related adverse events (irAE) between P and P+C groups. 71.6% in P vs 13.8% in P+C had PD-L1 TPS ≥50% (p < 0.001). There were no significant differences between the two groups in objective response rate (ORR), disease control rate (DCR), unadjusted progression-free survival (PFS) or unadjusted overall survival (OS) (Table). Multivariable adjustment for confounding factors between P+C vs P revealed no differences in OS [hazard ratio (HR) for death, 1.53, 95% CI 0.55 – 4.25] or PFS [HR for progression/death, 1.75, 95% CI 0.63 – 4.91]. Further stratification into PD-L1 TPS ≥50% and < 50% showed no significant differences between P+C vs. P in adjusted OS [HR for death, TPS < 50%- 1.54 (95% CI 0.59 – 4.03); TPS ≥50%- 0.71 (95% CI 0.11 – 4.52)] or PFS [HR for progression/death, TPS < 50%- 1.58 (95% CI 0.72 – 3.48); TPS ≥50%- 0.64 (95% CI 0.06 – 6.93)]. ECOG PS and development of irAE influenced OS in all groups, while TMB was relevant in PD-L1 ≥50% only. Conclusions: Our study shows no significant differences in outcomes with P vs P+C in advanced NSCLC in a real-world setting, albeit with limitations of single-center design, limited sample size, different line settings and lack of disease burden stratification. Ongoing phase III trials comparing front line P vs P+C will definitively address the long-term clinical benefits -if any- of combining cytotoxic chemotherapy with anti-PD-1 drugs. [Table: see text]

9533 Background: Pembrolizumab (P) is now widely used as standard of care (SOC) in advanced NSCLC. We sought to identify prognostic factors influencing survival with it in a real-world setting. Methods: We conducted a retrospective cohort study of with advanced NSCLC patients who initiated treatment with SOC P monotherapy at our center from 2/11/16 to 10/15/19 (data cutoff 1/15/20). Patient demographic, clinicopathologic, therapeutic and outcomes data were extracted. Survival time was defined from start of P. Cox proportional hazards and logistic regression were utilized. Results: Of 74 patients with median follow up of 83.9 weeks, 30 (40.5%) were alive at cutoff. Patient characteristics at start of therapy were: 36 (48.6%) female, median age 68.5 yr (range 33-87), 10 (13.5%) with symptomatic brain metastases; 54 (72.9%) treatment-naïve, 29 (39.2%) with ECOG performance status (PS) ≥2. Tumor characteristics were: 53 (71.6%) with PD-L1 tumor proportion score (TPS) ≥50%, median PD-L1 TPS 75% (range 1-100), tumor mutational burden (TMB) tested in only 37 (50%) patients, median TMB 8 mut/mB (range 1-62). Any grade immune-related adverse events (irAE) occurred in 33 (44.6%) patients, while 16 (21.6%) received systemic steroids. Median survival was 43.3 wks (95% CI 29-104.1). Multivariable regression showed ECOG PS of ≥2 as the strongest risk factor for death (Table). We next evaluated differences in characteristics of patients who were alive vs dead within 12 wks of starting P, by which initial response assessments are completed in routine practice. ECOG PS was the only significantly different baseline variable, even after multivariable adjustment (p = 0.002). Conclusions: ECOG PS of ≥2 is a poor prognostic risk factor associated with P monotherapy in advanced NSCLC. Though comprising a clinically significant subset of patients in real-world, they were not included in landmark trials (KEYNOTE-024 & 042). Prospective evaluation is warranted. [Table: see text]