Adjusted comparison of outcomes between patients from CARTITUDE-1 versus multiple myeloma patients with prior exposure to proteasome inhibitors, immunomodulatory drugs and anti-CD38 antibody from the prospective, multinational LocoMMotion study of real-world clinical practice

Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell therapy studied in patients with multiple myeloma exposed to three classes of treatment in the single-arm CARTITUDE-1 study. To assess the effectiveness of cilta-cel compared to real-world clinical practice (RWCP), we perfor...

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Published inHaematologica (Roma) Vol. 108; no. 8; pp. 2192 - 2204
Main Authors Mateos, Maria-Victoria, Weisel, Katja, Martin, Thomas, Berdeja, Jesús G, Jakubowiak, Andrzej, Stewart, A Keith, Jagannath, Sundar, Lin, Yi, Diels, Joris, Ghilotti, Francesca, Thilakarathne, Pushpike, Perualila, Nolen J, Cabrieto, Jedelyn, Haefliger, Benjamin, Erler-Yates, Nichola, Hague, Clare, Jackson, Carolyn C, Schecter, Jordan M, Strulev, Vadim, Nesheiwat, Tonia, Pacaud, Lida, Einsele, Hermann, Moreau, Philippe
Format Journal Article
LanguageEnglish
Published Italy Fondazione Ferrata Storti 01.08.2023
Ferrata Storti Foundation
Subjects
Cell Therapy & Immunotherapy
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Summary:Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell therapy studied in patients with multiple myeloma exposed to three classes of treatment in the single-arm CARTITUDE-1 study. To assess the effectiveness of cilta-cel compared to real-world clinical practice (RWCP), we performed adjusted comparisons using individual patients' data from CARTITUDE-1 and LocoMMotion, a prospective, multinational study of patients with multiple myeloma triple-class exposed of treatment. Comparisons were performed using inverse probability weighting. In CARTITUDE-1, 113 patients were enrolled, and 97 patients were infused with cilta-cel. In LocoMMotion, 248 patients were enrolled, and 170 patients were included in the comparisons versus infused patients. Ninety-two unique regimens were used in LocoMMotion, most frequently carfilzomib-dexamethasone (13.7%), pomalidomide-cyclophosphamide-dexamethasone (13.3%) and pomalidomidedexamethasone (11.3%). Adjusted comparisons showed that patients treated with cilta-cel were 3.12-fold more likely to respond to treatment than those managed by RWCP (response rate, 3.12, 95% confidence interval [95% CI]: 2.24-4.00), had their risk of progression or death reduced to by 85% (progression-free survival hazard ratio=0.15, 95% CI: 0.08-0.29), and a risk of death lowered by 80% (overall survival hazard ratio HR=0.20, 95% CI: 0.09-0.41). The incremental improvement in healthrelated quality of life from baseline for cilta-cel versus RWCP at week 52, as measured by EORTC QLQ-C30 Global Health Status, was 13.4 (95% CI: 3.5-23.6) and increased to 30.8 (95% CI: 21.8-39.8) when including death as additional information regarding patients' health status. Patients treated with cilta-cel experienced more adverse events than those managed with RWCP (any grade: 100% vs. 83.5%). The results from this study demonstrate improved efficacy outcomes of cilta-cel versus RWCP and highlight its potential as a novel and effective treatment option for patients with multiple myeloma triple-class exposed of antimyeloma treatment. CARTITUDE-1 is registered with clinicaltrials gov. Identifier: NCT03548207. LocoMMotion is registered with clinicaltrials gov. Identifier: NCT04035226.
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Disclosures
MVM has received honoraria from and is a member on boards of directors/advisory committees for Janssen, Celgene, Takeda, and Amgen; has received honoraria from Adaptive; and is a member on boards of directors/advisory committees for GSK, AbbVie, EDO, and Pharmamar. KW is a member on boards of directors/advisory committees for Amgen, Celgene, Janssen, and Sanofi; is a consultant for and receives honoraria from BMS and Takeda); has provided consultancy for Adaptive Biotech and Juno. TM has received research funding from Janssen, Amgen, and Sanofi and acts as a consultant for Oncopeptides and GSK. JGB has received research funding from AbbVie, Amgen, Acetylon, Bluebird, Bristol Myers Squibb, Celgene, Cellularity, Constellation, CRISPR, Therapeutics, CURIS, EMD Serono, Genentech, Glenmark, Janssen, Kesios, Lilly, Novartis, Poseida, Teva, Takeda Pharmaceuticals, and Vivolux; and has acted as a consultant for Amgen, Bioclinica, Bristol Myers Squibb, Celgene, CRISPR Therapeutics, Janssen, Karyopharm, Kite Pharma, Legend, Prothena, Servier, Takeda Pharmaceuticals, and SecuraBio. AJ has received consulting fees and honoraria from AbbVie, Adaptive, Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Juno, Karyopharm, and Sanofi; and is a member of a board of directors or advisory committee for AbbVie, Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, and Sanofi. AKS has received honoraria from Aventis, Janssen, Amgen, Oncopeptides, Bristol Myers Squibb, GlaxoSmithKline, and Sanofi; and is a member of a board of directors or advisory committee for Genomics England and Tempus. SJ is a consultant for Bristol Myers Squibb, Janssen, Karyopharm Therapeutics, Merck, Sanofi, Legend Biotech, and Takeda Pharmaceuticals. YL has provided consultancy services for Bluebird Bio, Celgene, Gamida Cells, Janssen, Huno, Kite, Novartis, Sorrento, Legend BioTech, and Vineti; and has received research funding from Bluebird Bio, Celgene, Janssen, Kite, Merck, and Takeda Pharmaceuticals. JD, FG, PT, NJP, JC, NEY, CH, JMS, and VS are employees of Janssen. BH was a previous employee of Janssen. CCJ is employed with Janssen; and is a consultant physician at the Memorial Sloan Kettering Cancer Center (New York, NY, USA). TN and LP are employees of Legend Biotech. HE has no conflicts of interest to disclose. PM has received consultancy fees and/or honoraria from Celgene, Janssen, Amgen, Takeda, and AbbVie.
MVM, KW, JD, BH, NEY, CH, and VS conceived the study. JD, FG, PT, BH, and NEY were responsible for the methodology. JD, FG, PT, NJP, and JC were responsible for software and formal analysis. MVM, KW, TM, JGB, AJ, AKS, SJ, YL, CCJ, JMS, VS, HE, and PM conducted the investigation. MVM, KW, TM, JGB, AJ, AKS, SJ, YL, JD, CH, CCJ, JMS, VS, HE, and PM organized resources. MVM, KW, JD, FG, PT, NJP, JC, CCJ, JMS, VS, and PM curated the data. JD, FG, PT, and BH wrote and prepared the original draft of the manuscript. MVM, KW, TM, JGB, AJ, AKS, SJ, YL, JD, FG, PT, NJP, JC, BH, NEY, CH, CCJ, JMS, VS, TN, LP, HE, and PM wrote, reviewed and/or edited the manuscript. JD, FG, PT, and BH contributed to the visualization. MVM, KW, JD, CH, JMS, and PM supervised the study. The project administrators were BH and NEY. All authors read and agreed to the published version of the manuscript.
Contributions
Data used for this study were derived from the CARTITUDE-1 and LocoMMotion studies. CARTITUDE-1 data-sharing is governed by the Janssen Pharmaceutical Companies of Johnson & Johnson’s data-sharing policy that is available online. As noted in the policy, requests for access to the study data can be submitted through Yale Open Data.
Data-sharing statement
ISSN:0390-6078
1592-8721
DOI:10.3324/haematol.2022.280482