Peri–CAR-T practice patterns and survival predictors for all CAR-T patients and post–CAR-T failure in aggressive B-NHL

• Published in: Blood advances 2023-06, Vol.7 (12), p.2657-2669
• Main Authors: Zurko, Joanna, Nizamuddin, Imran, Epperla, Narendranath, David, Kevin, Cohen, Jonathon B., Moyo, Tamara K., Ollila, Thomas, Hess, Brian, Roy, Ishan, Ferdman, Robert, Liu, Jieqi, Chowdhury, Sayan Mullick, Romancik, Jason, Bhansali, Rahul S., Harris, Elyse I., Sorrell, Mckenzie, Masel, Rebecca, Kittai, Adam S., Denlinger, Nathan, Sigmund, Audrey M., Fitzgerald, Lindsey, Galvez, Carlos, Ma, Shuo, Winter, Jane, Pro, Barbara, Gordon, Leo I., Danilov, Alexey, Stephens, Deborah, Shah, Nirav N., Kenkre, Vaishalee, Barta, Stefan K., Torka, Pallawi, Shouse, Geoffrey, Karmali, Reem
• Format: Article
• Language: English
• Subjects: Clinical Trials and Observations; Humans; Immunotherapy, Adoptive - methods; Lymphoma, B-Cell; Progression-Free Survival; Receptors, Chimeric Antigen - therapeutic use; Retrospective Studies
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2022008240

•Bridging therapy and more lines of pre–CAR-T therapy were associated with inferior PFS and OS after CAR-T for aggressive B-cell lymphoma.•Post–CAR-T failure, the median PFS of first-line therapies was 2.8 months with the most active regimen, with a median PFS of only 5.5 months. [Display omitted] Most patients receiving chimeric antigen receptor T-cell therapy (CAR-T) for aggressive B-cell non-Hodgkin lymphoma (B-NHL) do not experience a durable remission. Several novel agents are approved to treat relapsed, refractory aggressive B-NHL; however, it remains unclear how to sequence these therapies pre– and post–CAR-T. We conducted a multicenter retrospective analysis to describe peri–CAR-T practice patterns and survival predictors for patients receiving CD19-directed CAR-T. Patients (n = 514) from 13 centers treated with CAR-T for B-NHL between 2015-2021 were included in the study. Survival curves were constructed using Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the impact of the variables on survival outcomes. For all patients receiving CAR-T, a greater number of lines of therapy pre-CAR-T apheresis and bridging therapy were predictive of inferior progression-free survival (PFS) and overall survival (OS). The median PFS and OS from the time of CAR-T cell infusion were 7.6 and 25.6 months, respectively. From the time of progression post–CAR-T, the median OS was 5.5 months. The median PFS of treatments administered in the first-line post–CAR-T failure was 2.8 months. Patients with refractory disease on day 30 had inferior OS and were less likely to receive subsequent treatment(s) than other patients with CAR-T failure. Allogeneic hematopoietic cell transplantation for selected patients at any time following CAR-T failure led to durable responses in over half of patients at 1 year. These data provide a benchmark for future clinical trials in patients with post–CAR-T cell progression, which remains an unmet clinical need.