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

• Type of Material: Article
• Authors: Ajay Major, University of Chicago; Jovian Yu, University of Chicago; Navika Shukla, University of Chicago; Yan Che, University of Chicago; Theodore G. Karrison, University of Chicago; Rachel Treitman, University of Colorado; Manali K. Kamdar, University of Colorado; Bradley M. Haverkos, University of Colorado; James Godfrey, City of Hope Comprehensive Cancer Center; Melissa A. Babcook, Ohio State University; Timothy J. Voorhees, Ohio State University; Sophie Carlson, University of California Los Angeles; Daria Gaut, University of California Los Angeles; Caspian Oliai, University of California Los Angeles; Jason Romancik, Emory University; Allison M. Winter, Cleveland Clinic; Brian T. Hill, Cleveland Clinic; Radhika Bansal, Mayo Clin Rochester; Jose C. Villasboas Bisneto, Mayo Clin Rochester; Imran A. Nizamuddin, Northwestern University; Reem Karmali, Northwestern University; Lindsey A. Fitzgerald, University of Utah; Deborah M. Stephens, University of Utah; Priyanka A. Pophali, University of Wisconsin; Asaad Trabolsi, University of Miami; Jonathan H. Schatz, University of Miami; Marie Hu, University of Minnesota; Veronika Bachanova, University of Minnesota; Michael J. Slade, Washington University in St. Louis; Nathan Singh, Washington University in St. Louis; Nausheen Ahmed, Washington University in St. Louis; Joseph P. McGuirk, University of Kansas; Michael R. Bishop, University of Chicago; Peter A. Riedell, University of Chicago; Justin Kline, University of Chicago
• Language: English
• Date: 2023-08-22
• Publisher: ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by The American Society of Hematology.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2023010016
• Title of Journal or Parent Work: BLOOD ADVANCES
• Volume: 7
• Issue: 16
• Start Page: 4528
• End Page: 4538
• Grant/Funding Information: This work was supported by a grant from the National Cancer Institute (NCI) (T32CA009566) (A.M.).
• Keywords: THERAPY; Science & Technology; Life Sciences & Biomedicine; Hematology; CLASSIFICATION
• Research Categories: Biology, Cell; Health Sciences, Oncology

Abstract

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.