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Clinical Trial
. 2021 Jun 18;11(6):116.
doi: 10.1038/s41408-021-00507-2.

KarMMa-RW: comparison of idecabtagene vicleucel with real-world outcomes in relapsed and refractory multiple myeloma

Sundar Jagannath  1 , Yi Lin  2 , Hartmut Goldschmidt  3 , Donna Reece  4 , Ajay Nooka  5 , Alicia Senin  6 , Paula Rodriguez-Otero  7 , Ray Powles  8 , Kosei Matsue  9 , Nina Shah  10 , Larry D Anderson Jr  11 , Matthew Streetly  12 , Kimberly Wilson  13 , Hoa Van Le  13 , Arlene S Swern  13 , Amit Agarwal  13 , David S Siegel  14
Affiliations
Clinical Trial

KarMMa-RW: comparison of idecabtagene vicleucel with real-world outcomes in relapsed and refractory multiple myeloma

Sundar Jagannath et al. Blood Cancer J. .

Abstract

Patients with relapsed and refractory multiple myeloma (RRMM) who are triple-class exposed (to an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody) have limited treatment options and there is no standard of care. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy, demonstrated efficacy in triple-class exposed RRMM patients in the KarMMa trial (NCT03361748). In this retrospective study (KarMMa-RW), patient-level data from triple-class exposed RRMM patients were merged into a single data model and compared with KarMMa using trimmed stabilized inverse probability of treatment weighting. Endpoints included overall response rate (ORR; primary), rate of very good partial response or better (≥VGPR), progression-free survival (PFS), and overall survival (OS). Of 1949 real-world triple-class exposed RRMM patients, 190 received subsequent (index) line of therapy and met KarMMa eligibility criteria (Eligible RRMM cohort). With a median follow-up of 13.3 months in KarMMa and 10.2 months in Eligible RRMM, ORR, and ≥VGPR were significantly improved in KarMMa versus Eligible RRMM (ORR, 76.4% vs 32.2%; ≥VGPR, 57.9% vs 13.7%; both P < 0.0001) as were PFS (11.6 vs 3.5 months; P = 0.0004) and OS (20.2 vs 14.7 months; P = 0.0006). This study demonstrated that ide-cel significantly improved responses and survival compared with currently available therapies in triple-class exposed RRMM.

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Conflict of interest statement

S.J. served as a consultant for Bristol Myers Squibb (BMS), Janssen, Legend Biotech, Sanofi, and Takeda. Y.L. served as a consultant for Kite/Gilead, Celgene (a BMS Company), Juno Therapeutics (a BMS Company), bluebird bio, Janssen, Legend Biotech, Gamida Cells, and Novartis; received research funding from Kite/Gilead, Celgene (a BMS Company), bluebird bio, Janssen, Merck, and Takeda; is a member of Sorrento Therapeutics Data and Safety Monitoring Board. H.G. received grants and/or provision of investigational medicinal product from Amgen, BMS, Celgene (a BMS Company), Chugai, Dietmar-Hopp-Foundation, Janssen, Johns Hopkins University, and Sanofi; received research funding from Amgen, BMS, Celgene (a BMS Company), Chugai, Janssen, Incyte, Molecular Partners, Merck, Sharp and Dohme, Sanofi, Mundipharma, Takeda, and Novartis; served as a member of advisory board for Adaptive Biotechnologies, Amgen, BMS, Janssen, Sanofi, and Takeda; participated in the speakers’ bureau for Amgen, BMS, Celgene (a BMS Company), Chugai, GlaxoSmithKline (GSK), Janssen, Novartis, and Sanofi. D.R. served as a consultant for Celgene (a BMS Company), Janssen, Takeda, Amgen, and Karyopharm; received honoraria from Celgene (a BMS Company), Janssen, Takeda, and Amgen; received research funding from Celgene (a BMS Company), Janssen, Takeda, Otsuka, Merck, and BMS; provided expert testimony for Celgene (a BMS Company) and Amgen. A.N. served as a consultant for Spectrum Pharmaceuticals, BMS, Adaptive Biotechnologies, Amgen, Celgene (a BMS Company), Takeda, Karyopharm, Oncopeptides, GSK, and Janssen; received research funding from BMS, Amgen, Celgene (a BMS Company), Takeda, Karyopharm, GSK, and Janssen. P.R.O. served as a consultant for Celgene (a BMS Company), Janssen, AbbVie, Kite Pharma, and Sanofi; participated in the speakers’ bureau for Celgene (a BMS Company), Janssen, and Amgen; received travel funding from Celgene (a BMS Company). K.M. received honoraria from Celgene (a BMS Company), Takeda, and Janssen. N.S. served as a consultant for Genentech, Seagen Inc., Oncopeptides, Karyopharm, Surface Oncology, Precision Biosciences, GSK, Nektar, Amgen, Indapta Therapeutics, Sanofi, and BMS; received research funding from Celgene (a BMS Company), Janssen, bluebird bio, Sutro Biopharma, and Teneobio. L.D.A. served as a consultant for Amgen, BMS, GSK, Janssen, and Karyopharm; received research funding and honoraria from GSK, BMS, Janssen, Karyopharm, and Amgen. K.W., H.V.L., A.A. are employees and equity owners with BMS. A.S.S. was an employee of BMS at the time the work was completed. D.S.S. served as a consultant for Amgen, Celgene (a BMS Company), Takeda, Janssen, BMS, Karyopharm, and Merck; participated in the speakers’ bureau for Amgen, Celgene (a BMS Company), Takeda, Janssen, and BMS; received research funding from Celgene (a BMS Company); is an equity owner with Celularity. A.S., R.P., and M.S. declare no conflict of interest.

Figures

Fig. 1
Fig. 1. Selection process for real-world Eligible Cohort.
Collection of patient-level data from clinical sites, the Connect MM Registry, and external research databases, and a description of the selection process for the Eligible RRMM cohort in the KarMMa-RW study. *Baseline was defined as when patients became refractory to their last regimen. †Across all ide-cel target doses in the KarMMa study (ClinicalTrials.gov: NCT03361748); at the data cutoff of 30 October 2019, 58 patients (45.3%) had discontinued from the study, 31 (24.2%) due to death, 26 (20.3%) due to study withdrawal, and 1 (0.8%) lost to follow-up. ‡Overall, 108 patients (56.8%) discontinued from the study, all due to death. §Numbers (ranges) of matched patients from 30 imputed datasets. COTA denotes the COTA real-world evidence database, ECOG Eastern Cooperative Oncology Group, GRN Guardian Research Network, RRMM relapsed and refractory multiple myeloma.
Fig. 2
Fig. 2. Progression-free survival.
A shows a Kaplan–Meier curve of progression-free survival across all target doses and B shows a Kaplan–Meier curve of progression-free survival at the target dose of 450 × 106 CAR + T cells based on Independent Response Committee Review according to IMWG criteria applying Food and Drug Administration censoring rules. IMWG denotes International Myeloma Working Group, NE not estimable.
Fig. 3
Fig. 3. Overall survival.
A shows a Kaplan–Meier curve of overall survival across all target doses and B shows a Kaplan–Meier curve of overall survival at the target dose of 450 × 106 CAR + T cells based on Independent Response Committee Review according to IMWG criteria applying Food and Drug Administration censoring rules. IMWG denotes International Myeloma Working Group, NE not estimable.
Fig. 4
Fig. 4. Subgroup analyses of overall response rate and progression-free survival.
A shows overall response rate (confirmed partial response or better) by patient demographics and disease characteristics. B shows progression-free survival by patient demographics and disease characteristics. Patients with a partial response or better according to International Myeloma Working Group criteria applying Food and Drug Administration censoring rules were included. Multiple imputations were performed to create 30 datasets; estimates for the analyses were then obtained using Rubin’s rule to combine the individual estimates from each dataset. *Double-class refractory was defined as refractory to an immunomodulatory agent and a proteasome inhibitor. ORR denotes overall response rate, PFS progression-free survival.
See this image and copyright information in PMC

References

    1. Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, et al. Estimating the global cancer incidence and mortality in 2018: Globocan sources and methods. Int J Cancer. 2019;144:1941–53. doi: 10.1002/ijc.31937. - DOI - PubMed
    1. Rajkumar SV, Kumar S. Multiple myeloma: diagnosis and treatment. Mayo Clin Proc. 2016;91:101–19. doi: 10.1016/j.mayocp.2015.11.007. - DOI - PMC - PubMed
    1. Nijhof IS, van de Donk NWCJ, Zweegman S, Lokhorst HM. Current and new therapeutic strategies for relapsed and refractory multiple myeloma: an update. Drugs. 2018;78:19–37. doi: 10.1007/s40265-017-0841-y. - DOI - PMC - PubMed
    1. Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28:1122–8. doi: 10.1038/leu.2013.313. - DOI - PMC - PubMed
    1. Jagannath S, Rifkin RM, Gasparetto CJ, Toomey K, Durie B, Hardin JW, et al. Treatment journeys of patients with newly diagnosed multiple myeloma (NDMM): results from the connect MM registry. Clin Lymphoma Myeloma Leuk. 2020;20:272–6. doi: 10.1016/j.clml.2019.10.002. - DOI - PubMed

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