Real-world outcomes of brexucabtagene autoleucel (brexu-cel) for relapsed or refractory (R/R) mantle cell lymphoma (MCL): A CIBMTR subgroup analysis by prior treatment.
Year: 2023
Type: conference-abstract
Abstract: 7507 Background: Brexu-cel is a CAR T therapy approved for adult patients (pts) with R/R MCL. In a 3-year follow-up of ZUMA-2 (Wang et al., 2022), ORR was 91% (CR 68%). Median DOR, PFS and OS were 28.2, 25.8 and 46.6 mo respectively. Here, we describe real-world outcomes of brexu-cel by receipt of prior BTK inhibitor (BTKi), bendamustine, autoHCT, and 1-2 vs ≥ 3 prior lines of therapy. Methods: From 07/2020-08/2022, 397 pts receiving brexu-cel for R/R MCL from 79 US centers were registered in the CIBMTR observational database. In this analysis, 272 were included (median follow-up 6.6 mo; range 0.3-16.5), excluding pts 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); pts 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 seen in 69% (n = 111/160), 44% (n = 70/160) and 19% (n = 29/153) of pts respectively. Pts had a median of 4 lines of prior therapy (range 1-12; 6% as 2L). Prior to leukapheresis, 87% were BTKi-exposed; 54% received bendamustine; 31% were autoHCT recipients. Median time from leukapheresis to infusion was 28 d (IQR 26-34 d), during which 18% received bridging therapy. ORR for all was 89% (CR 78%). At 6 mo, cumulative incidence of relapse/PD was 21%; DOR, PFS and OS were 76%, 73% and 83% respectively. Grade ≥ 3 (ASTCT consensus) CRS and ICANS occurred in 9% and 27% of pts (88% and 62% for any grade). Most CRS (94%) and ICANS (79%) resolved within 3 weeks. Prolonged cytopenia by 30 d occurred in 23% pts. NRM at 100 d and 180 d were 3% and 6% respectively, mainly due to infections. ORR for BTKi-naïve (n = 36) vs -exposed (n = 233) pts was 85% (CR 79%; 6-mo DOR 84%) vs 89% (CR 77%; 6-mo DOR 74%); for pts with (n = 145) vs without (n = 124) prior bendamustine was 88% (CR 75%; 6-mo DOR 75%) vs 89% (CR 80%; 6-mo DOR 77%); for pts with (n = 83) vs without (n = 188) prior autoHCT was 90% (CR 82%; 6-mo DOR 83%) vs 88% (CR 76%; 6-mo DOR 72%). Higher CR rates were seen in pts with brexu-cel as 2/3L (n = 56) vs 4L+ (n = 213) (91% vs 74%; ORR 92% vs 88%; 6-mo DOR 77% vs 75%). Similar safety profiles were seen regardless of prior BTKi or autoHCT. Pts with prior bendamustine had fewer Grade ≥ 3 ICANS (19% vs 36%) but more prolonged cytopenia (29% vs 16%) vs pts without. Conclusions: These early findings suggest that real-world outcomes of 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. SK and NA contributed equally.
Source: Journal of Clinical Oncology
Authors: Swetha Kambhampati, Nausheen Ahmed, Mehdi Hamadani, Natalie Sophia Grover, Mazyar Shadman, Frederick L. Locke, James M. Gerson, Matthew Joshua Frank, Lihua Elizabeth Budde, Michael Wang, Zhen-Huan Hu, Ana Nunes, David Dalton, Ioana Kloos, Daniel Lee, Hairong Xu, Marcelo C. Pasquini, Alex Francisco Herrera
Institutions: City Of Hope National Medical Center, University of Kansas Medical Center, Medical College of Wisconsin, University of North Carolina at Chapel Hill, Fred Hutch Cancer Center, Moffitt Cancer Center, University of Vermont Medical Center, Stanford Medicine, Stanford University, The University of Texas MD Anderson Cancer Center, Kite (United States)
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4379340754