CD19 CAR T-cell therapy and prophylactic anakinra in relapsed or refractory lymphoma: Phase 2 trial interim results Journal Article
| Authors: | Park, J. H.; Nath, K.; Devlin, S. M.; Sauter, C. S.; Palomba, M. L.; Shah, G.; Dahi, P.; Lin, R. J.; Scordo, M.; Perales, M. A.; Shouval, R.; Tomas, A. A.; Cathcart, E.; Mead, E.; Santomasso, B.; Holodny, A.; Brentjens, R. J.; Riviere, I.; Sadelain, M. |
| Article Title: | CD19 CAR T-cell therapy and prophylactic anakinra in relapsed or refractory lymphoma: Phase 2 trial interim results |
| Abstract: | In preclinical models, anakinra, an IL-1 receptor antagonist (IL-1Ra), reduced immune effector cell-associated neurotoxicity syndrome (ICANS) without compromising anti-CD19 chimeric antigen receptor (CAR) T-cell efficacy. We initiated a phase 2 clinical trial of anakinra in patients with relapsed/refractory large B-cell lymphoma and mantle cell lymphoma treated with commercial anti-CD19 CAR T-cell therapy. Here we report a non-prespecified interim analysis reporting the final results from cohort 1 in which patients received subcutaneous anakinra from day 2 until at least day 10 post-CAR T-cell infusion. The primary endpoint was the rate of severe (grade ≥3) ICANS. Key secondary endpoints included the rates of all-grade cytokine release syndrome (CRS) and ICANS and overall disease response. Among 31 treated patients, 74% received axicabtagene ciloleucel, 13% received brexucabtagene ciloleucel and 4% received tisagenlecleucel. All-grade ICANS occurred in 19%, and severe ICANS occurred in 9.7% of patients. There were no grade 4 or 5 ICANS events. All-grade CRS occurred in 74%, and severe CRS occurred in 6.4% of patients. The overall disease response rate was 77% with 65% complete response rate. These initial results show that prophylactic anakinra resulted in a low incidence of ICANS in patients with lymphoma receiving anti-CD19 CAR T-cell therapy and support further study of anakinra in immune-related neurotoxicity syndromes. © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc. |
| Keywords: | adult; clinical trial; phase 2 clinical trial; interleukin 1 receptor blocking agent; pathology; lymphoma, large b-cell, diffuse; adoptive immunotherapy; immunotherapy, adoptive; cd19 antigen; antigens, cd19; interleukin 1 receptor antagonist protein; procedures; diffuse large b cell lymphoma; neurotoxicity syndromes; humans; human; toxicity and intoxication; cell-associated neurotoxicity |
| Journal Title: | Nature Medicine |
| Volume: | 29 |
| Issue: | 7 |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-07-01 |
| Start Page: | 1710 |
| End Page: | 1717 |
| Language: | English |
| DOI: | 10.1038/s41591-023-02404-6 |
| PUBMED: | 37400640 |
| PROVIDER: | scopus |
| PMCID: | PMC11462637 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Jae Park -- Source: Scopus |
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