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After CAR T-Cell Therapy for Diffuse Large B-Cell Lymphoma: What’s Next?

By: Gavin Calabretta, BS
Posted: Thursday, June 23, 2022

Anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy is a new and highly efficacious treatment modality for relapsed or refractory diffuse large B-cell lymphoma (DLBCL), but data evaluating treatments that work after patients relapse on CAR19 are scarce. For this reason, Audrey M. Sigmund, MD; Nathan Denlinger, DO; and Adam S. Kittai, MD, of The Ohio State University Comprehensive Cancer Center, Columbus, and colleagues retrospectively analyzed 120 patients with DLBCL who received CAR19, to determine what therapies elicited responses after CAR19 failure, and what prognostic markers could predict these responses. According to this single-center study, which was published in Transplantation and Cellular Therapy, patients who responded to CAR19 treatment were more likely to respond to salvage treatment outcomes than nonresponders. The authors also found no significant difference in outcomes based on the salvage regimen used.

Of the 120 total patients, 47% had primary refractory disease, 24% had MYC rearrangement, and 16% had high-grade disease with translocations of MYC, BCL2, and/or BCL6. The median age across all patients was 61 years, and the median number of prior treatment lines was three. A total of 47% of patients received axicabtagene ciloleucel, and 53% of patients received tisagenlecleucel.

Median overall survival for all patients who received salvage therapy was 14.4 months, and when the investigators assessed each salvage treatment received, there was no salvage treatment that appeared to prolong survival compared with another. The investigators observed that patients who underwent salvage therapy and responded to CAR19 had a significantly improved overall survival compared with patients who underwent salvage therapy and did not respond to CAR19, with a median overall survival of not reached and 10.9 months, respectively. In further analyses, patients with high levels of lactate dehydrogenase were significantly less likely to respond to salvage treatment (odds ratio = 0.07, 95% CI = 0.02–0.32, P = .0007) and had higher mortality risk (hazard ratio = 4.05, 95% CI = 1.40–11.68, P =.0097).

Disclosure: For full disclosures of the study authors, visit astctjournal.org.


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