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Five-Year Follow-Up of Standard-of-Care Axicabtagene Ciloleucel for Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium.

Five-Year Follow-Up of Standard-of-Care Axicabtagene Ciloleucel for Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Jain, M. D., Spiegel, J. Y., Nastoupil, L. J., Tamaresis, J., Ghobadi, A., Lin, Y., Lekakis, L., Reagan, P., Oluwole, O., McGuirk, J., Deol, A., Dorritie, K. A., Sehgal, A. R., Goy, A., Hill, B. T., Andreadis, C., Munoz, J., Ulrickson, M., Westin, J., Chavez, J. C., Patel, D., Jacobs, M. T., Bansal, R., Bennani, N. N., Patel, V. G., Rapoport, A. P., Vose, J. M., Miklos, D. B., Neelapu, S. S., Locke, F. L., Lunning, M., Dahiya, S. 2024: JCO2302786

Abstract

PURPOSE: Axicabtagene ciloleucel (axi-cel) is an autologous CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for the treatment of relapsed or refractory large B-cell lymphoma. Little is known about the long-term survivorship after CAR T-cell therapy.METHODS: We previously reported the results of 298 patients who were leukapheresed with the intent to receive standard-of-care axi-cel (n = 275 infused) after two or more previous lines of therapy at a median follow-up of 12.9 months. Here, we report extended follow-up of this cohort to a median of 58 months, with a focus on late survivorship events.RESULTS: Among axi-cel-infused patients, progression-free survival at 5 years was 29% and overall survival (OS) at 5 years was 40%. The 5-year lymphoma-specific survival was 53% with infrequent late relapses. However, the 5-year nonrelapse mortality (NRM) was 16.2%, with over half of NRM events occurring beyond 2 years. Patients who were 60 years and older had a lower risk of relapse (P = .02), but a higher risk of NRM compared with patients younger than 60 years (NRM odds ratio, 4.5 [95% CI, 2.1 to 10.8]; P < .001). Late NRM was mainly due to infections and subsequent malignant neoplasms (SMNs). In total, SMNs occurred in 24 patients (9%), including therapy-related myeloid neoplasms (n = 15), solid tumors (n = 7), and unrelated lymphoid malignancies (n = 2).CONCLUSION: In the standard-of-care setting, axi-cel exhibits outcomes consistent with those reported in clinical trials, with sustained, durable responses observed at the 5-year time point. However, late infections and the development of SMN are key survivorship issues that reduce long-term survival after CAR T-cell therapy, particularly in the elderly.

View details for DOI 10.1200/JCO.23.02786

View details for PubMedID 39094076