Comparison of Cilta-cel, an Anti-BCMA CAR-T Cell Therapy, Versus Conventional Treatment in Patients With Relapsed/Refractory Multiple Myeloma.


Journal

Clinical lymphoma, myeloma & leukemia
ISSN: 2152-2669
Titre abrégé: Clin Lymphoma Myeloma Leuk
Pays: United States
ID NLM: 101525386

Informations de publication

Date de publication:
05 2022
Historique:
received: 06 08 2021
revised: 19 10 2021
accepted: 22 10 2021
pubmed: 30 11 2021
medline: 28 4 2022
entrez: 29 11 2021
Statut: ppublish

Résumé

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). 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. 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. Cilta-cel yielded significantly improved outcomes versus real-world therapies in triple-class exposed patients with relapsed/refractory MM.

Sections du résumé

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.

Identifiants

pubmed: 34840088
pii: S2152-2650(21)02416-2
doi: 10.1016/j.clml.2021.10.013
pii:
doi:

Substances chimiques

Antibodies, Monoclonal 0
Receptors, Chimeric Antigen 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

326-335

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Auteurs

Luciano J Costa (LJ)

O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL. Electronic address: ljcosta@uabmc.edu.

Yi Lin (Y)

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN.

R Frank Cornell (RF)

Department of Medicine, Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN.

Thomas Martin (T)

Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.

Saurabh Chhabra (S)

Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI.

Saad Z Usmani (SZ)

Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute-Atrium Health, Charlotte, NC.

Sundar Jagannath (S)

Department of Medicine, Mount Sinai Medical Center, New York, NY.

Natalie S Callander (NS)

Carbone Cancer Center, University of Wisconsin, Madison, WI.

Jesus G Berdeja (JG)

Center for Blood Cancers, Sarah Cannon Research Institute, Nashville, TN.

Yubin Kang (Y)

Department of Medicine, Duke University School of Medicine, Durham, NC.

Ravi Vij (R)

Department of Medicine, Oncology Division, Washington University School of Medicine in St Louis, St Louis, MO.

Kelly N Godby (KN)

O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL.

Ehsan Malek (E)

Seidman Cancer Center, University Hospitals, Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA.

Amarendra Neppalli (A)

Department of Medicine, Medical University of South Carolina, Charleston, SC.

Michaela Liedtke (M)

Department of Medicine, Division of Hematology, Stanford University, Stanford, CA.

Mark Fiala (M)

Department of Medicine, Oncology Division, Washington University School of Medicine in St Louis, St Louis, MO.

Hong Tian (H)

Clinical Development, Cellular Therapy Program, Janssen R&D, Raritan, NJ.

Satish Valluri (S)

Market Access, Janssen Global Services, Raritan, NJ.

Jennifer Marino (J)

Clinical Research, Early Oncology Development, Janssen R&D, Spring House, PA.

Carolyn C Jackson (CC)

Clinical Development, Cellular Therapy Program, Janssen R&D, Raritan, NJ.

Arnob Banerjee (A)

Clinical Research, Early Oncology Development, Janssen R&D, Spring House, PA.

Ankit Kansagra (A)

Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX.

Jordan M Schecter (JM)

Clinical Development, Cellular Therapy Program, Janssen R&D, Raritan, NJ.

Shaji Kumar (S)

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN.

Parameswaran Hari (P)

Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI.

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