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Jeremy S. Abramson, MD, MMSc
Jeremy S. Abramson, MD, MMSc
Posted: Tuesday, January 21, 2025
Based on a multicenter retrospective study, molecular features traditionally associated with inferior outcomes did not seem to significantly influence responses or survival outcomes in patients with relapsed or refractory mantle cell lymphoma who underwent CD19-directed chimeric antigen receptor (CAR) T-cell therapy. Zachary D. Epstein-Peterson, MD, of Weill Cornell Medical College and Memorial Sloan Kettering Cancer Center, New York, and colleagues presented their findings at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 4393).
The investigators focused on 88 patients from five international centers who were predominantly treated outside of a clinical trial. With a median follow-up of 18 months, the 1-year overall and progression-free survival rates were 64% and 59%, respectively. Overall survival and progression-free survival from the time of infusion were not found to be associated with the following factors: blastoid or pleomorphic morphology; median Ki67 score of higher than 60%; any percentage of p53 expression; SOX11 expression; 17p deletion; Mindbomb homolog (MIB) Ib group at apheresis; and the lactate dehydrogenase level before lymphodepletion.
Based on next-generation sequencing data, which were obtained from a subset of the study population before CAR T-cell therapy, TP53 and ATM alterations did not appear to be significantly associated with the previously mentioned outcomes. Receipt of bridging therapy (66% of patients) was the only evaluated feature found to be associated with inferior progression-free (hazard ratio [HR] = 2.39) and overall (HR = 2.16) survival. Patients with mutant TP53 vs wild-type disease demonstrated a lower complete response rate; however, the difference did not seem to meet statistical significance (74% vs 96%; P = .053).
“Our findings, which warrant confirmation in larger genomically characterized cohorts, highlight the utility of CAR [T-cell therapy] even in patients with high-risk mantle cell lymphoma features,” the investigators concluded. “These data also underscore the pressing need for identifying novel biomarkers to inform on resistance mechanisms and predict treatment success.”
Disclosure: For full disclosures of the study authors, visit ash.confex.com.
2024 ASH Annual Meeting & Exposition
