Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma.

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 immunomodulatory 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. (Funded by bluebird bio and Celgene, a Bristol-Myers Squibb company; KarMMa ClinicalTrials.gov number, NCT03361748.).

• Authors: Nikhil C Munshi, Larry D Anderson Jr, Nina Shah, Deepu Madduri, Jesús 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 Petrocca, Monica Massaro, Jamie N Connarn, Shari Kaiser, Payal Patel, Liping Huang, Timothy B Campbell, Kristen Hege, Jesús San-Miguel
• Journal: The New England journal of medicine (N Engl J Med) Vol. 384 Issue 8 Pg. 705-716 (02 25 2021) ISSN: 1533-4406 [Electronic] United States
• PMID: 33626253 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Massachusetts Medical Society.

Chemical References

• Biomarkers
• Receptors, Chimeric Antigen
• idecabtagene vicleucel

Topics

• Adult
• Aged
• Biomarkers (blood)
• Cytokine Release Syndrome (etiology)
• Drug Resistance, Neoplasm
• Female
• Hematologic Diseases (chemically induced)
• Humans
• Immunotherapy, Adoptive (adverse effects)
• Male
• Middle Aged
• Multiple Myeloma (immunology, therapy)
• Progression-Free Survival
• Receptors, Chimeric Antigen (therapeutic use)
• Recurrence