Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results

Sham Mailankody, Jeffrey V. Matous, Saurabh Chhabra, Michaela Liedtke, Surbhi Sidana, Olalekan O. Oluwole, Shahbaz Malik, Rajneesh Nath, Faiz Anwer, Jose Carlos Cruz, Myo Htut, Erin E. Karski, Wade Lovelace, Myles Dillon, Eric Butz, Wendy Ying, Arun Balakumaran, Shaji K. Kumar

Research output: Contribution to journalArticlepeer-review

Abstract

ALLO-715 is a first-in-class, allogeneic, anti-BCMA CAR T cell therapy engineered to abrogate graft-versus-host disease and minimize CAR T rejection. We evaluated escalating doses of ALLO-715 after lymphodepletion with an anti-CD52 antibody (ALLO-647)-containing regimen in 43 patients with relapsed/refractory multiple myeloma as part A of the ongoing first-in-human phase 1 UNIVERSAL trial. Primary objectives included determination of the safety and tolerability of ALLO-715 and the safety profile of the ALLO-647-containing lymphodepletion regimen. Key secondary endpoints were response rate and duration of response. Grade ≥3 adverse events were reported in 38 (88.0%) of patients. Cytokine release syndrome was observed in 24 patients (55.8%), with 1 grade ≥3 event (2.3%) and neurotoxicity in 6 patients (14%), with no grade ≥3 events. Infections occurred in 23 patients (53.5%), with 10 (23.3%) of grade ≥3. Overall, 24 patients (55.8%) had a response. Among patients treated with 320 × 106 CAR+ T cells and a fludarabine-, cyclophosphamide- and ALLO-647-based lymphodepletion regimen (n = 24), 17 (70.8%) had a response including 11 (45.8%) with very good partial response or better and 6 (25%) with a complete response/stringent complete response. The median duration of response was 8.3 months. These initial results support the feasibility and safety of allogeneic CAR T cell therapy for myeloma.

Original languageEnglish (US)
Pages (from-to)422-429
Number of pages8
JournalNature Medicine
Volume29
Issue number2
DOIs
StatePublished - Feb 2023

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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