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CAR T-Cell Therapy for Large B-Cell Lymphoma: Promise and Precautions
Anti-CD19 CAR T-cell therapy is potentially curative for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), although long-term outcomes are incompletely understood. Investigators report updated, 5-year results of a multicenter retrospective analysis of axicabtagene ciloleucel (axi-cel) therapy in 275 patients who had received at least two prior lines of therapy. Bridging therapy was allowed prior to CAR T-cell administration; 43% of patients would not have been eligible for the registrational clinical trial that led to FDA approval of axi-cel.
Findings at a median follow-up of 58 months were as follows:
- The overall response rate was 82%, with complete response in 64%; three early deaths were related to CAR T-cell–associated toxicities.
- The 5-year progression-free survival was 29%, and 5-year overall survival was 40%.
- Of 118 progressions or relapses, 102 occurred within 2 years of CAR T-cell infusion, with only 5 after year 3.
- Nonrelapse mortality was 16.2% at 5 years, mostly due to infections and second primary malignancies, and continued to occur throughout the years following the CAR T-cell product infusion.
- Patients aged 60 and older had a lower incidence of lymphoma relapse, but higher nonrelapse mortality, than younger patients.
Comment
This real-world analysis confirms CAR T-cell therapy as a curative approach in R/R LBCL, while identifying prolonged immunodeficiency and severe infections as well as late second primary cancers. About half of the latter were treatment-related myeloid malignancies, at least in part due to prior chemotherapy. The shift of CAR T-cell therapy to patients with first relapse and less-extensive prior lymphoma therapy, and better approaches to immune reconstitution, may mitigate some late nonrelapse mortality events.
Citation(s)
Author:
Jain MD et al.
Title:
Five-year follow-up of standard-of-care axicabtagene ciloleucel for large B-cell lymphoma: Results from the US Lymphoma CAR T Consortium.
Source:
J Clin Oncol
2024
Oct
20; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
Michael E. Williams, MD, ScM