Comparison of outcomes with ciltacabtagene autoleucel (cilta-cel) in CARTITUDE-1 versus real-world standard of care (RW SOC) for patients (pts) with triple-class exposed relapsed/refractory multiple myeloma (RRMM).

Thomas G. Martin UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA info_outline Thomas G. Martin, Amrita Y. Krishnan, Kwee Yong, Katja Weisel, Maneesha Mehra, Sandhya Nair, Keqin Qi, Anil Londhe, Joris Diels, Concetta Crivera, Carolyn Chang Jackson, Yunsi Olyslager, Martin Vogel, Jordan Mark Schecter, Arnob Banerjee, Satish Valluri, Saad Zafar Usmani, Jesus G. Berdeja, Sundar Jagannath

Authors Thomas G. Martin UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA info_outline Thomas G. Martin, Amrita Y. Krishnan, Kwee Yong, Katja Weisel, Maneesha Mehra, Sandhya Nair, Keqin Qi, Anil Londhe, Joris Diels, Concetta Crivera, Carolyn Chang Jackson, Yunsi Olyslager, Martin Vogel, Jordan Mark Schecter, Arnob Banerjee, Satish Valluri, Saad Zafar Usmani, Jesus G. Berdeja, Sundar Jagannath Organizations UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, City of Hope Comprehensive Cancer Center, Duarte, CA, University College Hospital, London, United Kingdom, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, Janssen Global Services, LLC, Raritan, NJ, Janssen Pharmaceutica NV, Beerse, NJ, Belgium, Janssen R&D, LLC, Titusville, NJ, Janssen R&D, LLC, Yardley, PA, Janssen R&D, Raritan, NJ, Janssen Pharmaceutica NV, Beerse, Belgium, Janssen R&D, Spring House, PA, Levine Cancer Institute/Atrium Health, Charlotte, NC, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN, Mount Sinai Medical Center, New York, NY Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Janssen Research & Development, LLC Background: Pts with RRMM who are triple-class exposed (to immunomodulatory drugs [IMiDs], proteasome inhibitors [PIs] and an anti-CD38 antibody) cycle through multiple salvage regimens with progressively worse outcomes. CARTITUDE-1 (NCT03548207) is a single-arm phase 1b/2 study evaluating cilta-cel, a chimeric antigen receptor T-cell therapy with 2 B-cell maturation antigen–targeting single-domain antibodies, in pts with RRMM who received ≥3 prior lines of therapy (LOT) or were double refractory to an IMiD and PI, were triple-class exposed, had ECOG score of 0 or 1, and had disease progression ≤12 mo after the last LOT. Here, we compare efficacy outcomes for pts who received cilta-cel in CARTITUDE-1 (N = 97) with pts treated with SOC in a synthetic cohort from RW clinical practice. Methods: The Flatiron database, a primarily US community-based MM registry (Sep 2020 data cutoff), was used to identify a RW pt cohort who met CARTITUDE-1 (Sep 2020 data cutoff) eligibility criteria, including organ function. Progression-free/overall survival (PFS/OS) were compared between the cilta-cel–treated US pts and RW SOC cohort, using inverse probability of treatment (tx) weighting (IPTW) propensity scores adjusting for unbalanced baseline covariates of prognostic significance. Sensitivity analyses were conducted using multivariate Cox regression models and propensity score matching. Results: Baseline characteristics were similar between the 2 cohorts after propensity score weighting (Table). SOC tx regimens in the RW cohort primarily included pomalidomide (33%), carfilzomib (32%), daratumumab (13%), elotuzumab (16%), and ixazomib (8%). Pts had improved PFS and OS with cilta-cel (N = 97; median follow-up 12.4 mo) vs RW SOC (N = 196; median follow-up 9.2 mo) with a reduction in risk of progression/death and death by 84% and 78%, respectively (Table). Cilta-cel treatment benefit was robust across sensitivity analyses. Conclusions: Cilta-cel shows significantly better efficacy outcomes over RW SOC for PFS and OS, highlighting its potential as an effective tx option in pts with triple-class exposed RRMM. Clinical trial information: NCT03548207 CARTITUDE-1 N = 97 RW Cohort Observed N = 196 RW Cohort IPTW-Adjusted N = 102 Baseline characteristic, % Age < 65 y 64 41 67 < 6 y since MM diagnosis 46 81 44 High-risk cytogenetics* 24 18 22 ISS stage III 14 32 11 Prior LOT > 4 66 69 73 Time to progression on last LOT ≤4 mo 50 29 52 Triple-class refractory only † 45 43 43 Outcomes PFS, HR (95% CI) ‡ 0.17 (0.11, 0.26) § 0.16, (0.10, 0.27) § OS, HR (95% CI) ‡ 0.26 (0.15, 0.46) § 0.22 (0.11, 0.45) § *del17p, t(14;16), t(4;14); † At least 1 PI, at least 1 IMiD, and 1 anti-CD38 antibody; ‡ CARTITUDE-1 vs RW cohort; § P ≤ 0.0001. CI, confidence interval; HR, hazard ratio.