S220: real-world outcomes of brexucabtagene autoleucel (brexu-cel) for relapsed or refractory mantle cell lymphoma: a cibmtr subgroup analysis by prior treatment

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Brexu-cel is a chimeric antigen receptor (CAR) T-cell therapy approved for adult patients with relapsed/refractory mantle cell lymphoma (r/r MCL). In a 3-year follow-up of ZUMA-2 (Wang et al., 2022), the objective response rate (ORR) was 91% (complete response [CR] rate, 68%). Median duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were 28.2, 25.8 and 46.6 months, respectively. Aims: To describe real-world outcomes with brexu-cel analyzed by prior receipt of BTK inhibitor (BTKi), bendamustine, or autologous hematopoietic cell transplant (autoHCT), and 1–2 vs ≥3 prior lines (L) of therapy. Methods: From July 2020 to August 2022, 397 patients who received brexu-cel for r/r MCL in 79 US centers were registered in the Center for International Blood and Marrow Transplant Research (CIBMTR) observational database. In this analysis, 272 patients were included (median follow-up, 6.6 months; range, 0.3–16.5), excluding patients with prior non-HCT cellular therapy (n=7), missing data on prior treatment, or no follow-up. Descriptive analyses were used for all outcomes. Results: Median age was 65.8 years (range, 34.1–84.9); patients were mostly male (78%). Prior to infusion, 7% had ECOG PS ≥2; 76% had clinically significant comorbidities; 4% had extranodal CNS involvement. At diagnosis, Ki-67 ≥30%, Ki-67 ≥50%, and TP53/17p deletion were reported in 69% (n=111/160), 44% (n=70/160), and 19% (n=29/153) of patients, respectively. Patients had a median of 4 lines of prior therapy (range, 1–12; 6% as 2L). Prior to leukapheresis, 87% of patients were BTKi-exposed; 54% received bendamustine; and 31% were autoHCT recipients. Median time from leukapheresis to infusion was 28 days (IQR, 26–34 days), during which 18% of patients received bridging therapy. Overall ORR was 89% (CR rate, 78%). At 6 months, cumulative incidence of relapse/progressive disease was 21%; DOR, PFS, and OS were 76%, 73%, and 83%, respectively. Grade ≥3 (ASTCT consensus) cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 9% and 27% of patients, respectively (88% and 62% for any grade). Most CRS (94%) and ICANS (79%) resolved within 3 weeks. Prolonged cytopenia by 30 days occurred in 23% of patients. Non-relapse mortality rates at 100 days and 180 days were 3% and 6%, respectively, mainly due to infections. ORR in BTKi-naive (n=36) vs -exposed (n=233) patients was 85% (CR rate, 79%; 6-month DOR, 84%) vs 89% (CR rate, 77%; 6-month DOR, 74%). ORR in patients with (n=145) vs without (n=124) prior bendamustine was 88% (CR rate, 75%; 6-month DOR, 75%) vs 89% (CR rate, 80%; 6-month DOR, 77%). ORR in patients with (n=83) vs without (n=188) prior autoHCT was 90% (CR rate, 82%; 6-month DOR, 83%) vs 88% (CR rate, 76%; 6-month DOR, 72%). Higher CR rates were reported in patients with brexu-cel as 2/3L (n=56) vs 4L+ (n=213) (91% vs 74%; ORR, 92% vs 88%; 6-month DOR, 77% vs 75%). Similar safety profiles were observed regardless of prior BTKi or autoHCT. Patients with prior bendamustine had reduced incidence of Grade ≥3 ICANS (19% vs 36%) but increased prolonged cytopenia (29% vs 16%) vs those without. Summary/Conclusion: These early findings suggest that real-world outcomes with brexu-cel are consistent regardless of prior BTKi, bendamustine, or autoHCT. Use of brexu-cel in earlier lines may help achieve a higher CR rate. Further studies with longer follow-up are warranted to contextualize response rates in relation to long-term clinical benefits of brexu-cel. Updated data with longer follow-up will be reported at the time of presentation. Keywords: Real world data, Mantle cell lymphoma, CAR-T