Outcomes in Patients With Aggressive B-Cell Lymphoma With Progressive Disease Following CAR T-Cell Therapy

Despite advances in novel therapies, survival rates remain poor for patients with relapsed/refractory aggressive B-cell lymphoma who develop progressive disease following CD19-directed chimeric antigen receptor (CAR) T-cell therapy, according to a study conducted by Joanna C. Zurko, MD, and colleagues, and presented at the 2021 American Society of Hematology Annual Meeting.

This study consisted of 400 patients who received anti-CD19 CAR T-cell therapy between 2015 and 2020 across 12 U.S. academic medical centers. The investigators collated demographic and clinical characteristics of the study population along with CAR T-cell therapy toxicities and response. Univariate analyses were performed to determine the impact of demographic and clinical variables on survival outcomes, the researchers noted.

According to the results, in the entire cohort, median progression-free survival (PFS) and overall survival (OS) from time of CAR T-cell infusion were 11 months and 27 months, respectively. Analyses showed that patients who received three or more lines of therapy before CAR T-cell infusion and those with refractory disease pre-infusion had both markedly worse PFS (p = 0.004 and p = 0.001) and OS (both p < 0.001).

Results showed that at 22.4 months follow-up, almost half (48%) of patients had progressive disease following CAR T-cell therapy. The investigators noted that, of patients with progressive disease, median PFS and OS from time of disease progression was just 83 days in patients who received salvage therapy and 174 days for all patients, respectively.

Furthermore, the results showed that median PFS was highest for in patients treated with polatuzumab vedotin plus bendamustine-rituximab (4.5 months; n = 14), followed by bispecific antibodies (2.5 months; n = 8), lenalidomide with or without an anti-CD20 antibody (1.8 months; n = 13), checkpoint inhibitors (1.6 months; n = 10), BTK inhibitors (1.2 months; n = 8), radiation alone (1.2 months; n = 17), chemotherapy (1.1 months; n = 12), and tafasitamab plus lenalidomide (0.9 months; n = 5). The median PFS for all treated patients was 1.8 months.

Twelve patients in the study (6.3%) later received an allogeneic hematopoietic cell transplant (alloHCT), and 10 were evaluated for response. The results showed that seven achieved CR and five remain in CR.

“AlloHCT remains a potential curative therapy for select patients with over half with durable remission; however, few ultimately received alloHCT,” the researchers concluded. “Despite increased use of novel therapies, survival in patients who progress after CAR T-cell therapy is still dismal warranting more effective therapies.