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

Ajay Major, Jovian Yu, Navika Shukla, Yan Che, Theodore G. Karrison, Rachel Treitman, Manali K. Kamdar, Bradley M. Haverkos, James Godfrey, Melissa A. Babcook, Timothy J. Voorhees, Sophie Carlson, Daria Gaut, Caspian Oliai, Jason T. Romancik, Allison M. Winter, Brian T. Hill, Radhika Bansal, Jose C.Villasboas Bisneto, Imran A. NizamuddinReem Karmali, Lindsey A. Fitzgerald, Deborah M. Stephens, Priyanka A. Pophali, Asaad Trabolsi, Jonathan H. Schatz, Marie Hu, Veronika Bachanova, Michael J. Slade, Nathan Singh, Nausheen Ahmed, Joseph P. McGuirk, Michael R. Bishop, Peter A. Riedell, Justin Kline

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4528-4538
Number of pages11
JournalBlood Advances
Volume7
Issue number16
DOIs
StatePublished - Aug 16 2023

Bibliographical note

Publisher Copyright:
© 2023 by The American Society of Hematology.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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