TY - JOUR
T1 - Comparison of Cilta-cel, an Anti-BCMA CAR-T Cell Therapy, Versus Conventional Treatment in Patients With Relapsed/Refractory Multiple Myeloma
AU - Costa, Luciano J.
AU - Lin, Yi
AU - Cornell, R. Frank
AU - Martin, Thomas
AU - Chhabra, Saurabh
AU - Usmani, Saad Z.
AU - Jagannath, Sundar
AU - Callander, Natalie S.
AU - Berdeja, Jesus G.
AU - Kang, Yubin
AU - Vij, Ravi
AU - Godby, Kelly N.
AU - Malek, Ehsan
AU - Neppalli, Amarendra
AU - Liedtke, Michaela
AU - Fiala, Mark
AU - Tian, Hong
AU - Valluri, Satish
AU - Marino, Jennifer
AU - Jackson, Carolyn C.
AU - Banerjee, Arnob
AU - Kansagra, Ankit
AU - Schecter, Jordan M.
AU - Kumar, Shaji
AU - Hari, Parameswaran
N1 - Funding Information:
Editorial support was provided by Joanna Bloom, PhD, of Eloquent Scientific Solutions, and funded by Janssen Global Services, LLC. The CARTITUDE-1 study and these analyses were funded by Janssen Research & Development, LLC, and Legend Biotech, Inc.
Funding Information:
L.J. Costa reports consulting or advisory roles for AbbVie, Amgen, Celgene, and Karyopharm Therapeutics; serving on speakers bureaus for Amgen and Sanofi; receiving honoraria from Amgen, Celgene, Janssen, Karyopharm Therapeutics, and Sanofi; and receiving research funding from Janssen and Amgen. Y. Lin reports consulting or advisory roles for Bluebird Bio, Bristol-Myers Squibb, Celgene, GamidaCell, Janssen, Juno Therapeutics, Kite/Gilead, Legend Biotech, Novartis, Sorrento Therapeutics, and Vineti; and receiving research funding from Bluebird Bio, Bristol-Myers Squibb, Janssen, and Kite/Gilead. R.F. Cornell is employed by and has stock or ownership interests in AbbVie. T. Martin reports consulting or advisory roles for GlaxoSmithKline and Juno Therapeutics; and receiving research funding from Amgen, Janssen, and Sanofi. S. Chhabra reports research funding from Amgen, Janssen, and Sanofi. S.Z. Usmani reports consulting or advisory roles for AbbVie, Amgen, Celgene, GlaxoSmithKline, Janssen, Karyopharm Therapeutics, Merck, Seattle Genetics, Skyline Diagnostics, and Takeda; serving on speakers bureaus for Celgene, Janssen, Sanofi, and Takeda; and receiving research funding from Amgen, Array BioPharma, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, and Skyline Diagnostics. S. Jagannath reports consulting or advisory roles for Bristol-Myers Squibb, Janssen, Karyopharm Therapeutics, Legend Biotech, Sanofi, and Takeda; and receiving travel funding from Bristol-Myers Squibb, Janssen, Karyopharm Therapeutics, and Legend Biotech. N.S. Callander reports research funding from Celectar. J.G. Berdeja reports consulting or advisory roles for Bluebird Bio, Bristol-Myers Squibb, Celgene, CRISPR Therapeutics, Janssen, Kite/Gilead, Legend Biotech, Secura Bio, and Takeda; and receiving research funding from AbbVie, Acetylon Pharmaceuticals, Amgen, Bluebird Bio, Bristol-Myers Squibb, Celator Pharmaceuticals, Celgene, Celularity, CRISPR Therapeutics, CURIS, EMD Serono, Genentech/Roche, Ichnos Sciences, Incyte, Janssen, Juno, Kesios Therapeutics, Lilly, Novartis, Poseida, Sanofi, Takeda, Teva, and Vivolux. Y. Kang reports consulting or advisory roles for Sanofi and Takeda; having stock or ownership interests in Ionis; and receiving research funding from Incyte. R. Vij reports consulting or advisory roles for Bristol-Myers Squibb, Celgene, Genentech/AbbVie, Janssen, Karyopharm Therapeutics, Oncopeptides, Sanofi, and Takeda; receiving travel funding from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, DAVA Oncology, Janssen, Karyopharm Therapeutics, Sanofi, and Takeda; and receiving research funding from Bristol-Myers Squibb, Celgene, and Takeda. E. Malek reports consulting or advisory roles for Janssen, Sanofi, Amgen, Takeda, Celgene, Bristol-Myers Squibb, Karyopharm, and GlaxoSmithKline; serving on speakers bureaus for Janssen, Sanofi, Amgen, Takeda, Celgene, Bristol-Myers Squibb, Karyopharm, and GlaxoSmithKline; and receiving research funding from Amgen, BlueSpark, MedPacto, and Clinigen. A. Neppalli reports consulting or advisory roles for Amgen and Sanofi. M. Liedtke reports consulting or advisory roles for GlaxoSmithKline, Sanofi, Oncopeptides, Kite, Alnylam, Karyopharm, Bristol-Myers Squibb, Kura Oncology, and Takeda; and receiving honoraria from Pfizer. H. Tian, S. Valluri, J. Marino, A. Banerjee, and J.M. Schecter are employed by and have stock or ownership interests in Johnson & Johnson. C.C. Jackson is employed by Johnson & Johnson, and reports serving in a consulting or advisory role for Memorial Sloan-Kettering Cancer Center. A. Kansagra reports consulting or advisory roles for Alnylam, Celgene, GlaxoSmithKline, Janssen, Karyopharm Therapeutics, Oncopeptides, Pfizer, Pharmacyclics, Sanofi, and Takeda. S. Kumar reports consulting or advisory roles for AbbVie, Amgen, Bluebird Bio, Celgene, Cellectar, Genecentrix, Genentech/Roche, Janssen, Kite/Gilead, Merck, Molecular Partners, Oncopeptides, and Takeda; and receiving research funding from AbbVie, CARsgen Therapeutics, Celgene, Janssen, Kite/Gilead, MedImmune, Merck, Novartis, Roche/Genentech, Sanofi, Takeda, and TeneoBio. P. Hari reports consulting or advisory roles for Amgen, Bristol-Myers Squibb, Janssen, Karyopharm Therapeutics, GSK, Kite/Gilead, Pharmacyclics, Sanofi, and Takeda; receiving honoraria from AbbVie/Pharmacyclics, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Incyte, Janssen, Karyopharm Therapeutics, Kite/Gilead, Novartis, Sanofi, and Takeda; and receiving research funding from Celgene, Millennium Pharmaceuticals. K.N. Godby and M. Fiala state they have no conflicts of interest.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2022/5
Y1 - 2022/5
N2 - Background: In the single-arm, phase 1b/2 CARTITUDE-1 study, ciltacabtagene autoleucel (cilta-cel), an anti-B-cell maturation antigen chimeric antigen receptor T-cell (CAR-T) therapy, showed encouraging efficacy in US patients with multiple myeloma (MM) who previously received an immunomodulatory drug, proteasome inhibitor, and anti-CD38 monoclonal antibody (triple-class exposed). Patients and Methods: A dataset of US patients refractory to an anti-CD38 monoclonal antibody (MAMMOTH) was used to identify patients who would meet eligibility for CARTITUDE-1 and received subsequent non-CAR-T therapy. The intent-to-treat (ITT) population in CARTITUDE-1 included patients who underwent apheresis (N = 113); the modified ITT (mITT) population was the subset who received cilta-cel (n = 97). Corresponding populations were identified from the MAMMOTH dataset: ITT population (n = 190) and mITT population of patients without progression/death within 47 days (median apheresis-to-cilta-cel infusion time) from onset of therapy (n = 122). Using 1:1 nearest neighbor propensity score matching to control for selected baseline covariates, 95 and 69 patients in CARTITUDE-1 ITT and mITT populations, respectively, were matched to MAMMOTH patients. Results: In ITT cohorts of CARTITUDE-1 vs. MAMMOTH, improved overall response rate (ORR; 84% vs. 28% [P <.001]) and longer progression-free survival (PFS; hazard ratio [HR], 0.11 [95% confidence interval (CI), 0.05-0.22]) and overall survival (OS; HR, 0.20 [95% CI, 0.10-0.39]) were observed. Similar results were seen in mITT cohorts of CARTITUDE-1 vs. MAMMOTH (ORR: 96% vs. 30% [P <.001]; PFS: HR, 0.02 [95% CI, 0.01-0.14]; OS: HR, 0.05 [95% CI, 0.01-0.22]) and with alternative matching methods. Conclusion: Cilta-cel yielded significantly improved outcomes versus real-world therapies in triple-class exposed patients with relapsed/refractory MM.
AB - Background: In the single-arm, phase 1b/2 CARTITUDE-1 study, ciltacabtagene autoleucel (cilta-cel), an anti-B-cell maturation antigen chimeric antigen receptor T-cell (CAR-T) therapy, showed encouraging efficacy in US patients with multiple myeloma (MM) who previously received an immunomodulatory drug, proteasome inhibitor, and anti-CD38 monoclonal antibody (triple-class exposed). Patients and Methods: A dataset of US patients refractory to an anti-CD38 monoclonal antibody (MAMMOTH) was used to identify patients who would meet eligibility for CARTITUDE-1 and received subsequent non-CAR-T therapy. The intent-to-treat (ITT) population in CARTITUDE-1 included patients who underwent apheresis (N = 113); the modified ITT (mITT) population was the subset who received cilta-cel (n = 97). Corresponding populations were identified from the MAMMOTH dataset: ITT population (n = 190) and mITT population of patients without progression/death within 47 days (median apheresis-to-cilta-cel infusion time) from onset of therapy (n = 122). Using 1:1 nearest neighbor propensity score matching to control for selected baseline covariates, 95 and 69 patients in CARTITUDE-1 ITT and mITT populations, respectively, were matched to MAMMOTH patients. Results: In ITT cohorts of CARTITUDE-1 vs. MAMMOTH, improved overall response rate (ORR; 84% vs. 28% [P <.001]) and longer progression-free survival (PFS; hazard ratio [HR], 0.11 [95% confidence interval (CI), 0.05-0.22]) and overall survival (OS; HR, 0.20 [95% CI, 0.10-0.39]) were observed. Similar results were seen in mITT cohorts of CARTITUDE-1 vs. MAMMOTH (ORR: 96% vs. 30% [P <.001]; PFS: HR, 0.02 [95% CI, 0.01-0.14]; OS: HR, 0.05 [95% CI, 0.01-0.22]) and with alternative matching methods. Conclusion: Cilta-cel yielded significantly improved outcomes versus real-world therapies in triple-class exposed patients with relapsed/refractory MM.
KW - B-cell maturation antigen
KW - CARTITUDE-1
KW - Chimeric antigen receptor T-cell therapy
KW - Ciltacabtagene autoleucel
KW - MAMMOTH
UR - http://www.scopus.com/inward/record.url?scp=85120376442&partnerID=8YFLogxK
U2 - 10.1016/j.clml.2021.10.013
DO - 10.1016/j.clml.2021.10.013
M3 - Article
C2 - 34840088
AN - SCOPUS:85120376442
SN - 2152-2650
VL - 22
SP - 326
EP - 335
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 5
ER -