A Single Center Retrospective Study of Real World Relapsed/Refractory DLBCL Patients Eligible for CAR T-Cell Therapy: Patient Characteristics and Outcomes

Introduction: Patients with Diffuse large B-cell lymphoma (DLBCL) may experience excellent long-term outcomes after initial anthracycline containing therapy. However, patients with relapsed or refractory (R/R) DLBCL often have poor outcomes. Select R/R DLBCL patients may be treated with additional chemoimmunotherapy(CIT) followed by hematopoietic stem cell transplant (HSCT). However, as many as 50% of R/R DLBCL patients are unable to undergo HSCT due to lack of response to CIT or comorbidities (Gisselbrecht C, et al JCO 2010). Recent data reported in the SCHOLAR-1 study suggest a median overall survival (OS) of 6.3 months for these patients, with only 20% of patients alive at 2 years (Crump M, et al Blood 2017). Chimeric antigen receptorT-cell (CAR-T) therapy, a novel form of immunotherapy, offers improved outcomes for such patients with complete response rates of approximately 40% and 50% OS at 12 months or greater (Neelapu SS et al. NEJM 2017; Borchmann P et al, EHA 2018). Delivery of CAR-T therapy is specialized and remains limited to a small number of centers at present. The broad applicability of CAR-T therapy in a real world population of R/R DLBCL patients remains unknown. This retrospective study aimed to identify the characteristics and outcomes of a cohort of R/R DLBCL patients who would have been eligible for CAR-T cell therapyif available over a 4 year period at Swedish Cancer Institute (SCI). The SCI is a specialty cancer research center, based in a non-profit, non-university affiliated medical center. Methods: All patients with recorded diagnosis of DLBCL (ICD9/10) seen for an outpatient encounter in a SCI facility between the dates of 01/01/2014 and 01/01/2018 were identified from an electronic medical record database. Patients who had received anthracycline-based chemotherapy only at SCI as initial therapy and then subsequently received 2 nd line or beyond therapy at SCI between January 2014 and January 2018 were included. This population was defined as the study cohort of R/R DLBCL patients and was then evaluated for would-be eligibility for CAR-T therapy by application of the defined KiteZuma-1 clinical trial Inclusion/Exclusion (I/E) criteria. Patient characteristics for the CAR-T eligible population were obtained by retrospective medical record review. Overall survival of the potential CAR-T eligible population was assessed including stratification by receipt of HSCT at any time during the study period. Results: 486 patients with a diagnosis of DLBCL were seen during outpatient SCI encounters between Jan 2014 and Jan 2018. Of these, 60 patients received prior 1 st line anthracycline therapy exclusively at SCI and then received 2 nd line or beyond therapy at SCI between 2014 and 2018 for R/R DLBCL. The majority of patients, 82% (n=49), met all Zuma-1 I/E criteria for CAR-T therapy. Characteristics of these patients are identified in Table 1. Among all CAR-T eligible patients, OS was 37.1% at 24 months (Figure 1). Patients received a variety of 2 nd line or beyond therapies, including 47% (n=23) who received HSCT. OS at 24 months for CAR-T eligible patients was significantly better for those receiving HSCT in 2 nd line or beyond versus those who did not receive HSCT (61.6% vs 12.0%, respectively; p Conclusion: In a retrospective cohort of real-world R/R DLBCL patients treated between 2014 and 2018 at SCI, a non-university based specialty cancer research center, 49 of 60 patients (82%) would have been eligible for CAR-T therapy based on Zuma 1 I/E criteria. This suggests that the majority of the patients with R/R DLBCL in the real-world may have an opportunity to receive CAR-T. Moreover, while those who underwent a successful HSCT as part of 2 nd line or beyond therapy had greatly improved outcomes, those patients who did not undergo HSCT had poor outcomes. For such patients not receiving HSCT, the availability of CAR -T may lead to significantly improved outcomes. Disclosures Pagel: Pharmacyclics, an AbbVie Company: Consultancy; Gilead: Consultancy. Bensinger: Janssen: Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; amgen: Speakers Bureau; Takeda: Speakers Bureau; celgene: Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau. Mawad: Swedish Cancer Institute: Employment. Patel: Pharmacyclics/Janssen: Speakers Bureau; Sunesis Pharmaceuticals: Consultancy; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; Celgene: Consultancy; Juno Therapeutics: Consultancy.