Real-world barriers to CAR-T access: A Canadian referral center perspective.
Authors: Shi Steven , Laverdure Eva , Cohen Sandra R. A. , Veilleux Olivier , Lachance Silvy , Mollica Luigina , Fleury Isabelle 
Published: June 2024

e19002 Background: CD19 chimeric antigen receptor T-cell (CAR-T) is the standard of care for patients with relapsed or refractory large B-cell lymphoma (LBCL) beyond second line therapy. Access to CAR-T remains a significant barrier for patients and is limited by the numbers of CAR-T centers, patient comorbidities and lymphoma kinetics. This study aims to define clinical features associated with CAR-T ineligibility and associated outcomes in a real-world setting. Methods: We conducted a single center retrospective study of all adult patients with R/R LBCL referred at Hôpital Maisonneuve-Rosemont in Montreal, Canada, for CAR-T between July 2019 and December 2023. Comprehensive data were gathered from electronic medical records. This study was approved by the institutional ethics committee. Results: A total of 235 patients were evaluated: 133 (57%) were infused, 10 (4%) were apheresed but not infused and 92 (39%) patients were deemed ineligible and further analyzed. The main reasons for ineligibility were ECOG performance score more than 1 (n=23), comorbidities (n=18), not R/R to two prior lines of therapy (LOT) (n=15) and rapid disease progression (n=15). Prohibitive comorbidities included: creatinine clearance <45ml/min (n=13), left ventricular ejection fraction <45% (n=2), unstable coronary artery disease (n=1), severe valvular disease (n=1) and Child B cirrhosis (n=1). 10 declined CAR-T and 10 were diagnosed or had lymphoma subtypes not covered by CAR-T reimbursement criteria: grade 3B follicular lymphoma (n=5), T-cell lymphoma (n=2), Hodgkin lymphoma (n=1), Richter from chronic lymphocytic leukemia (n=1) and transformed marginal zone lymphoma (n=1). 33 had more than one exclusion criteria. Median age at referral was 66 years (range: 25-87). Median IPI at diagnosis (available in 74%) was 3 (range: 0-5). At CAR-T evaluation, 77 patients had a stage 3 or 4 disease and 7 had CNS involvement. Median LOT for LBCL were 2 (range: 0-5), 46 were primary refractory and 23 relapsed within 12 months. 18 patients had undergone prior high dose therapy and autologous stem cell transplant (HDT-ASCT). 6 were exposed to novel therapies (polatuzumab=6, mosunetuzumab=2). Median follow-up after CAR-T exclusion was 4.25 months (range: 0-49.2). 50 (68% of patients with B-cell lymphoma R/R to at least 2 LOT) were deceased at time of analysis. Data on further LOT was available for 22 patients: 10 received novel therapies (tafasitamab=5, polatuzumab=3, mosunetuzumab=1, alectinib=1), 6 HDT-ASCT, 3 allogeneic stem cell transplant, 4 conventional chemotherapies and 2 radiation therapy. Conclusions: 39% of evaluated patients with R/R LBCL were ineligible for CAR-T mainly due to poor performance status, comorbidities and prohibitive progressive disease. Our study did not capture patients not referred due to geographical considerations but highlights dismal outcomes for patients ineligible for CAR-T. Widespread access to novel therapies is awaited.