ASH 2024: Poor Outcomes Observed Following Disease Progression After CD19-Directed CAR T-Cell Therapy

Chimeric antigen receptor (CAR) T-cell therapies have become a standard treatment option for many patients with relapsed or refractory mantle cell lymphoma (MCL). While these therapies are considered highly effective in this setting, many patients still relapse, and there is not much known about outcomes after disease progression post-CAR T-cell therapy. Investigators therefore analyzed patient records from 9 different institutions in the United States to better understand treatment patterns and outcomes following disease progression after CD19-directed CAR T-cell therapy. This research was presented by Foundation research grantee, Zachary D. Epstein-Peterson, MD of Memorial Sloan Kettering Cancer Center.

The analysis included data from 104 patients who experienced disease progression after brexucabtagene autoleucel (88%) or lisocabtagene maraleucel (12%). Among these patients, 71% had a complete response to initial CAR T-cell therapy and 13% had a partial response; 15% had no response. The median time from infusion to progression was 6 months.

After disease progression, 78 patients received a different systemic anti-lymphoma therapy. The most commonly used therapies were pirtobrutinib, chemoimmunotherapy, venetoclax, bispecific antibodies, and small molecule combinations. The overall response rate across all systemic therapies immediately post-CAR T-cell therapy was 42%, with the highest response rates seen with bispecific antibodies (60%) and small molecule combinations (50%).

With a median 15.2 months of follow-up, the median progression-free interval among these patients was 2.3 months and median overall survival was 5.4 months. Survival outcomes were worse in patients with TP53 tumor mutations, older adults (≥65 years of age), and those with no initial response to CAR T-cell therapy.

This study also included contributions from Foundation SAB members Kami J. Maddocks, MD of The Ohio State University; Gilles Salles, MD, PhD of Memorial Sloan Kettering Cancer Center; Andrew D. Zelenetz, MD, PhD of Memorial Sloan Kettering Cancer Center; and Foundation grantees Elise A. Chong, MD of the University of Pennsylvania; Andrew Ip, MD, MSc of Hackensack Meridian Health; Caron A. Jacobson, MD, MMSc of Dana-Farber Cancer Institute; Manali K. Kamdar, MD of University of Colorado; Reid W. Merryman, MD of Dana-Farber Cancer Institute; Javier Munoz, MD of Mayo Clinic, Phoenix; Peter A. Riedell, MD of University of Chicago; Christine E. Ryan, MD of Dana-Farber Cancer Institute; Roni Shouval, MD, PhD of Memorial Sloan Kettering Cancer Institute; Yucai Wang, MD, PhD of Mayo Clinic, Rochester; Samuel Yamshon, MD of Weill Cornell Medicine; Lia Palomba, MD of Memorial Sloan Kettering Cancer Center; Preetesh Jain, MD, MBBS, PhD, DM of The University of Texas MD Anderson Cancer Center; and Anita Kumar, MD of Memorial Sloan Kettering Cancer Center.