Idecabtagene vicleucel in relapsed and refractory multiple myeloma

Nikhil C. Munshi, Larry D. Anderson, Nina Shah, Deepu Madduri, Jesus Berdeja, Sagar Lonial, Noopur Raje, Yi Lin, David Siegel, Albert Oriol, Philippe Moreau, Ibrahim Yakoub-Agha, Michel Delforge, Michele Cavo, Hermann Einsele, Hartmut Goldschmidt, Katja Weisel, Alessandro Rambaldi, Donna Reece, Fabio PetroccaMonica Massaro, Jamie N. Connarn, Shari Kaiser, Payal Patel, Liping Huang, Timothy B. Campbell, Kristen Hege, Jesus San-Miguel

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

Abstract

BACKGROUND Idecabtagene vicleucel (ide-cel, also called bb2121), a B-cell maturation antigen- directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expected CAR T-cell toxic effects in patients with relapsed and refractory multiple myeloma. METHODS In this phase 2 study, we sought to confirm the efficacy and safety of ide-cel in patients with relapsed and refractory myeloma. Patients with disease after at least three previous regimens including a proteasome inhibitor, an immunomodulating agent, and an anti-CD38 antibody were enrolled. Patients received ide-cel target doses of 150 × 106 to 450 × 106 CAR-positive (CAR+) T cells. The primary end point was an overall response (partial response or better); a key secondary end point was a complete response or better (comprising complete and stringent complete responses). RESULTS Of 140 patients enrolled, 128 received ide-cel. At a median follow-up of 13.3 months, 94 of 128 patients (73%) had a response, and 42 of 128 (33%) had a complete response or better. Minimal residual disease (MRD)-negative status (<10-5 nucleated cells) was confirmed in 33 patients, representing 26% of all 128 patients who were treated and 79% of the 42 patients who had a complete response or better. The median progression-free survival was 8.8 months (95% confidence interval, 5.6 to 11.6). Common toxic effects among the 128 treated patients included neutropenia in 117 patients (91%), anemia in 89 (70%), and thrombocytopenia in 81 (63%). Cytokine release syndrome was reported in 107 patients (84%), including 7 (5%) who had events of grade 3 or higher. Neurotoxic effects developed in 23 patients (18%) and were of grade 3 in 4 patients (3%); no neurotoxic effects higher than grade 3 occurred. Cellular kinetic analysis confirmed CAR+ T cells in 29 of 49 patients (59%) at 6 months and 4 of 11 patients (36%) at 12 months after infusion. CONCLUSIONS Ide-cel induced responses in a majority of heavily pretreated patients with refractory and relapsed myeloma; MRD-negative status was achieved in 26% of treated patients. Almost all patients had grade 3 or 4 toxic effects, most commonly hematologic toxic effects and cytokine release syndrome.

Original languageEnglish (US)
Pages (from-to)705-716
Number of pages12
JournalNew England Journal of Medicine
Volume384
Issue number8
DOIs
StatePublished - Feb 25 2021
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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