Efficacy and Safety of Tisagenlecleucel in Patients with Relapsed/Refractory Follicular Lymphoma: A Real-World Analysis from the Center for Blood and Marrow Transplant Research (CIBMTR) Registry

Background: Tisagenlecleucel is an autologous CD19-directed chimeric antigen receptor (CAR)-T-cell therapy approved for the treatment of patients (pts) with relapsed/refractory (r/r) follicular lymphoma (FL) who have received ≥2 lines of prior therapy. In the initial report of the ELARA study, responses to tisagenlecleucel were high (overall response rate [ORR], 86.2%; complete response rate [CRR], 69.1%) and toxicity was mild (cytokine release syndrome [CRS], 48.5% any grade, no grade ≥3; immune effector cell-associated neurotoxicity syndrome [ICANS], 4.1% any grade, 1% grade ≥3). However, there are limited data regarding outcomes of r/r FL pts treated with commercial tisagenlecleucel. Here we present the first real-world data from the CIBMTR registry of pts with r/r FL treated with tisagenlecleucel in the US. Methods: Data were collected as a part of a noninterventional, prospective, longitudinal study using the CIBMTR registry. All pts received commercial tisagenlecleucel in the US after the FDA approval date of May 27, 2022. Efficacy outcomes included ORR, CRR, progression-free survival (PFS), duration of response (DOR), and overall survival (OS). Key safety outcomes included incidence and severity of adverse events (AEs), including CRS, ICANS, and cytopenias. Results: As of March 5, 2024, 92 pts had received tisagenlecleucel (infused set). Median age at infusion was 66.1 years (range: 36.4-83.4). All pts had a reported Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Seventy-five pts (81.5%) had a medical comorbidity, including diabetes (23.9%), pulmonary disease (20.7%), cardiac disease (16.3%), and renal disease (1.1%). Median number of prior therapies was 4 (range: 1-10); 20.7% of pts had primary refractory disease. Fludarabine + cyclophosphamide (68.5%) and bendamustine (23.9%) were the most common lymphodepleting chemotherapy regimens. Among pts with ≥100 days' follow-up evaluable for safety and efficacy (n=64), median follow-up was 6.7 months (range: 2.7-16.9). ORR was 90.6% (95% CI: 80.7-96.5) and CRR was 76.6%. Median DOR, PFS, and OS were not reached. Three- and 6-month PFS estimates were 87.4% (95% CI: 76.3-93.5) and 77.8% (95% CI: 64.6-86.5), respectively. Three- and 6-month OS estimates were 100% and 94.1% (95% CI: 82.7-98.1), respectively. Within 100 days of infusion, CRS, ICANS, and clinically significant infections were experienced by 62.5%, 20.3%, and 20.3% of pts, respectively. No cases of grade ≥3 CRS were reported. Median time to CRS onset was 2.0 days (range: 1.0-5.0). Twenty-eight of 40 pts who experienced CRS (70%) received treatment; all but one received tocilizumab to manage CRS (96.4%). Grade 3 and 4 ICANS were each experienced by 1 pt (1.6%). Median time to ICANS onset was 5.0 days (range: 1.0-7.0). All pts who experienced ICANS received treatment; corticosteroids were used to manage ICANS in 10 pts (76.9%). Six prolonged cytopenias (persisting >30 days) were reported: thrombocytopenia (n=5) and neutropenia (n=1); recovery at 3 months was experienced by 60% and 100% of pts, respectively. Two pts reported subsequent neoplasms (basal cell skin malignancy and squamous cell skin malignancy). Five deaths occurred >30 days post infusion: 4 due to disease progression, 1 due to acute respiratory distress syndrome (ARDS). Conclusions: In the first analysis of pts with r/r FL captured in the CIBMTR registry, pts treated with tisagenlecleucel experienced ORR and CRR similar to ELARA despite the high rate of comorbidities (81.5%) and a median of 4 prior therapies. Although numerically higher rates of any grade CRS and ICANS were reported, rates of grade ≥3 CRS and ICANS were similar to pts treated on ELARA. Early estimates of PFS and OS are encouraging. Additional exploratory analyses will be performed to identify predictors of efficacy and safety outcomes.