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. 2023 Feb 16;141(7):756-765.
doi: 10.1182/blood.2022017848.

Interventions and outcomes of patients with multiple myeloma receiving salvage therapy after BCMA-directed CAR T therapy

Oliver Van Oekelen  1   2 , Karthik Nath  3 , Tarek H Mouhieddine  1   4 , Tasmin Farzana  3 , Adolfo Aleman  1 , David T Melnekoff  1 , Yogita Ghodke-Puranik  1 , Gunjan L Shah  3   5 , Alexander Lesokhin  3   6 , Sergio Giralt  3   5 , Santiago Thibaud  1   4 , Adriana Rossi  1   4 , Cesar Rodriguez  1   4 , Larysa Sanchez  1   4 , Joshua Richter  1   4 , Shambavi Richard  1   4 , Hearn J Cho  1   4   7 , Ajai Chari  1   4 , Saad Z Usmani  3   5   6 , Sundar Jagannath  1   4 , Urvi A Shah  6 , Sham Mailankody  3   6 , Samir Parekh  1   4   8   9
Affiliations

Interventions and outcomes of patients with multiple myeloma receiving salvage therapy after BCMA-directed CAR T therapy

Oliver Van Oekelen et al. Blood. .

Abstract

B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR T) therapy has demonstrated remarkable efficacy in patients with relapsed/refractory multiple myeloma, and now there are two US Food and Drug Administration-approved BCMA-directed CAR T products. However, despite high initial response rates, most patients eventually relapse. The outcomes of patients with disease recurrence after BCMA-directed CAR T have not been comprehensively studied, and such an analysis would help define optimal treatment strategies. We analyzed the salvage treatments and outcomes of 79 patients with multiple myeloma from two academic institutions, who had progression of disease after treatment with BCMA-directed CAR T. A total of 237 post-CAR T salvage treatment lines were used, and patients received a median of 2 (range, 1-10) treatment lines. The median overall survival from the date of relapse post-CAR T therapy was 17.9 months (95% confidence interval [CI], 14.0 non-estimable). The overall response rate to the first salvage regimen was 43.4%, with a median progression-free survival of 3.5 months (CI, 2.5-4.6). Thirty-five patients (44.3%) received a T-cell-engaging therapy (bispecific antibody or subsequent CAR T) as salvage treatment. The overall survival in patients who received subsequent T-cell-engaging therapy was not reached after a median follow up of 21.3 months. Patients with multiple myeloma who relapse after BCMA-directed CAR T have a limited prognosis but can be potentially treated with multiple lines of salvage therapy. T-cell-engaging therapies appear to maintain pronounced clinical activity in this setting.

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Conflict of interest statement

Conflict-of-interest disclosure: T.H.M. reports advisory board fees from Legend Biotech; G.L.S. receives research funding from Janssen, Amgen, and Beyond Spring; A.L. reports grant funding from Genmab, Amgen, Bristol Myers Squibb, and Janssen, has served on an advisory panel for Trillium Therapeutics, Pfizer, and Bristol Myers Squibb, and has received research funding from Janssen Oncology, Trillium Therapeutics, Genentech, Bristol Myers Squibb, Sanofi, and Pfizer; S.G. receives research funding from Miltenyi Biotec, Takeda Pharmaceutical, Celgene, Amgen, Sanofi, Johnson & Johnson, Actinium Pharmaceuticals, and Omeros, and is a member on the advisory boards for Kite Pharma, Celgene, Sanofi, Novartis, Johnson & Johnson, Amgen, Takeda Pharmaceutical, Jazz Pharmaceuticals, Janssen, Actinium Pharmaceuticals, and Spectrum Pharma; A.C. reports research support from Amgen, Array Biopharma, Celgene, GSK, Janssen, Millennium/Takeda, Novartis Pharmaceuticals, Oncoceutics, Pharmacyclics, and Seattle Genetics, consultancy fees from Amgen, Bristol Myers Squibb, Celgene, Millennium/Takeda, Janssen, and Karyopharm, and membership on the scientific advisory board for Amgen, Celgene, Millennium/Takeda, Janssen, Karyopharm, Sanofi, and Seattle Genetics; S.Z.U. reports grants/personal fees from Amgen, Celgene, Sanofi, Seattle Genetics, Janssen, Takeda, Skyline DX, Merck, and GSK, grant funding from BMS and Pharmacyclics; and personal fees from AbbVie, MundiPharma, Gilead, Genentech, and Oncopeptides; S.J. reports consulting fees for Bristol Myers Squibb (Celgene), Janssen, Karyopharm Therapeutics, Merck, Sanofi, and Takeda Pharmaceuticals; U.A.S. reports consultancy fees from Janssen, grant funding from the Parker Institute for Cancer Immunotherapy, the International Myeloma Society, Paula and Rodger Riney Foundation, Allen Foundation Inc, HealthTree Foundation, Janssen, Celgene/BMS, and the MSK Paul Calabresi Career Development Award for Clinical Oncology K12CA184746 and payment for lectures including service on speaker bureaus from ACCC and MJH Life Sciences; S.M. has received consulting fees from Evicore, Optum, BioAscend, Janssen Oncology, and Legend Biotech; T.F., G.L.S., A.L., S.G., S.U., U.A.S., and S.M. report funding support from the National Cancer Institute Memorial Sloan Kettering Core Grant (P30 CA008748); Memorial Sloan Kettering Cancer Center receives research funding from the National Cancer Institute, Janssen Oncology, Bristol Myers Squibb, Allogene Therapeutics, Fate Therapeutics, and Takeda Oncology for the research conducted by S.M. He has received honoraria from OncLive, Physician Education Resource, MJH Life Sciences, and Plexus Communications; S.P. is supported by NCI R01 CA244899, R01 CA252222, P30 CA196521 and research funding from Bristol Myers Squibb (Celgene), Karyopharm, and Amgen; The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
OS after BCMA-directed CAR T relapse and PFS of the first line of salvage therapy. (A) OS curve. (B) PFS curve for first-line salvage therapy.
Figure 2.
Figure 2.
OS after BCMA-directed CAR T relapse stratified by disease characteristics. (A) OS curve, stratified by triple-class refractory status (defined as refractory to ≥1 immunomodulatory drug, ≥1 proteasome inhibitor, and ≥1 anti-CD38 monoclonal antibody). (B) OS curve, stratified by penta-drug refractory status (defined as refractory to ≥2 immunomodulatory drugs, ≥2 proteasome inhibitors, and ≥1 anti-CD38 mAb).
Figure 3.
Figure 3.
After BCMA-directed CAR T relapse, use of subsequent T-cell–engaging therapies can lead to durable responses. (A) OS curve for the 35 patients who received at least 1 instance of subsequent T-cell–engaging therapy (ie, CAR T and/or bispecific antibodies) at any time point after relapse on BCMA-directed CAR T. (B) PFS curve of first-line salvage therapy for the 13 patients who immediately transitioned onto a T-cell–engaging therapy after relapse to BCMA-directed CAR T therapy.
See this image and copyright information in PMC

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