Efficacy of checkpoint inhibition after CAR-T failure in aggressive B-cell lymphomas: outcomes from 15 US institutions.

Autor:	Major A; The University of Chicago Comprehensive Cancer Center, Chicago, IL.; University of Colorado Cancer Center, Aurora, CO., Yu J; The University of Chicago Comprehensive Cancer Center, Chicago, IL., Shukla N; The University of Chicago Comprehensive Cancer Center, Chicago, IL., Che Y; The University of Chicago Comprehensive Cancer Center, Chicago, IL., Karrison TG; The University of Chicago Comprehensive Cancer Center, Chicago, IL., Treitman R; University of Colorado Cancer Center, Aurora, CO., Kamdar MK; University of Colorado Cancer Center, Aurora, CO., Haverkos BM; University of Colorado Cancer Center, Aurora, CO., Godfrey J; City of Hope Comprehensive Cancer Center, Duarte, CA., Babcook MA; The Ohio State University James Comprehensive Cancer Center, Columbus, OH., Voorhees TJ; The Ohio State University James Comprehensive Cancer Center, Columbus, OH., Carlson S; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA., Gaut D; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA., Oliai C; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA., Romancik JT; Winship Cancer Institute at Emory University, Atlanta, GA., Winter AM; Taussig Cancer Institute at Cleveland Clinic, Cleveland, OH., Hill BT; Taussig Cancer Institute at Cleveland Clinic, Cleveland, OH., Bansal R; Mayo Clinic Rochester, Rochester, MN., Villasboas Bisneto JC; Mayo Clinic Rochester, Rochester, MN., Nizamuddin IA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL., Karmali R; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL., Fitzgerald LA; Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT., Stephens DM; Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT., Pophali PA; University of Wisconsin Carbone Cancer Center, Madison, WI., Trabolsi A; University of Miami Sylvester Comprehensive Cancer Center, Miami, FL., Schatz JH; University of Miami Sylvester Comprehensive Cancer Center, Miami, FL., Hu M; Masonic Cancer Center, University of Minnesota, Minneapolis, MN., Bachanova V; Masonic Cancer Center, University of Minnesota, Minneapolis, MN., Slade MJ; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO., Singh N; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO., Ahmed N; The University of Kansas Cancer Center, Kansas City, KS., McGuirk JP; The University of Kansas Cancer Center, Kansas City, KS., Bishop MR; The University of Chicago Comprehensive Cancer Center, Chicago, IL.; David and Etta Jonas Center for Cellular Therapy, The University of Chicago Medicine, Chicago, IL., Riedell PA; The University of Chicago Comprehensive Cancer Center, Chicago, IL.; David and Etta Jonas Center for Cellular Therapy, The University of Chicago Medicine, Chicago, IL., Kline J; The University of Chicago Comprehensive Cancer Center, Chicago, IL.; David and Etta Jonas Center for Cellular Therapy, The University of Chicago Medicine, Chicago, IL.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2023 Aug 22; Vol. 7 (16), pp. 4528-4538.
DOI:	10.1182/bloodadvances.2023010016
Abstrakt:	Checkpoint inhibitor (CPI) therapy with anti-PD-1 antibodies has been associated with mixed outcomes in small cohorts of patients with relapsed aggressive B-cell lymphomas after CAR-T failure. To define CPI therapy efficacy more definitively in this population, we retrospectively evaluated clinical outcomes in a large cohort of 96 patients with aggressive B-cell lymphomas receiving CPI therapy after CAR-T failure across 15 US academic centers. Most patients (53%) had diffuse large B-cell lymphoma, were treated with axicabtagene ciloleucel (53%), relapsed early (≤180 days) after CAR-T (83%), and received pembrolizumab (49%) or nivolumab (43%). CPI therapy was associated with an overall response rate of 19% and a complete response rate of 10%. Median duration of response was 221 days. Median progression-free survival (PFS) and overall survival (OS) were 54 and 159 days, respectively. Outcomes to CPI therapy were significantly improved in patients with primary mediastinal B-cell lymphoma. PFS (128 vs 51 days) and OS (387 vs 131 days) were significantly longer in patients with late (>180 days) vs early (≤180 days) relapse after CAR-T. Grade ≥3 adverse events occurred in 19% of patients treated with CPI. Most patients (83%) died, commonly because of progressive disease. Only 5% had durable responses to CPI therapy. In the largest cohort of patients with aggressive B-cell lymphoma treated with CPI therapy after CAR-T relapse, our results reveal poor outcomes, particularly among those relapsing early after CAR-T. In conclusion, CPI therapy is not an effective salvage strategy for most patients after CAR-T, where alternative approaches are needed to improve post-CAR-T outcomes. (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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