Impact of extranodal involvement at CAR T-cell therapy on outcomes in patients with relapsed or refractory large B-cell lymphoma—Results from a multicenter cohort study - Report - MDSpire
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Impact of extranodal involvement at CAR T-cell therapy on outcomes in patients with relapsed or refractory large B-cell lymphoma—Results from a multicenter cohort study
Impact of Extranodal Disease on CAR T-cell Therapy Outcomes in R/R Large B-cell Lymphoma
Overview
This multicenter retrospective study evaluated 218 patients with relapsed/refractory large B-cell lymphoma (LBCL) and extranodal (EN) involvement undergoing CAR T-cell therapy. The study found that EN disease is common and heterogeneous, with skin/soft tissue, bone, and lung being the most frequent sites. Overall response rate was 62%, with manageable toxicity profiles including cytokine release syndrome and neurotoxicity.
Background
Extranodal lymphoma involves sites outside lymph nodes and is present in up to 50% of diffuse large B-cell lymphoma (DLBCL) cases at diagnosis. EN DLBCL differs from nodal disease in molecular features, clinical presentation, and prognosis. CAR T-cell therapy has transformed treatment for relapsed/refractory LBCL, but data on outcomes in patients with EN involvement remain limited and conflicting. This study aimed to clarify outcomes and toxicities associated with EN disease in a large cohort receiving CAR T-cell therapy.
62% of patients had a single EN site involved, while 38% had two or more EN sites at CAR-T infusion.
Skin/soft tissue (25%), bone (22%), and lung (17%) were the most common EN sites.
The overall response rate to CAR T-cell therapy was 62%, with a complete response rate of 40%.
CRS occurred in 73% of patients, but only 6% experienced severe (grade ≥3) CRS.
Neurotoxicity (ICANS) was observed in 37% of patients, with 19% experiencing grade ≥3 ICANS.
Prolonged hematologic toxicities requiring transfusions or growth factors were common, with 19-20% needing prolonged red blood cell or platelet transfusions and 36% requiring prolonged G-CSF support.
Clinical Implications
Clinicians should recognize that EN involvement is frequent and heterogeneous in R/R LBCL patients undergoing CAR T-cell therapy. Despite the presence of EN disease, meaningful response rates and manageable toxicity profiles can be achieved. Close monitoring for hematologic toxicities and neurotoxicity is warranted, especially in patients with multiple EN sites.
Conclusion
This large multicenter study demonstrates that CAR T-cell therapy is effective and tolerable in patients with relapsed/refractory LBCL with extranodal involvement, supporting its use in this diverse patient population. Further research is needed to optimize management based on specific EN sites.
by Frederique St-Pierre, Subodh Bhatta, Peter G. Doukas, Madeline Jenkin, Kaitlin Annunzio, Alexandra E. Rojek, Alyssa Gibson, Yun Kyoung Tiger, Brittany McCall, Khaled Alhamad, Alec Hansen, Juan P. Alderuccio, Olutobi Adewale, Keem Patel, Asaad Trabolsi, Izidore S. Lossos, Lindsey Fitzgerald, Thomas A. Ollila, Matthew J. Matasar, Justin Kline, Reem Karmali, Narendranath Epperla
