Comparative effectiveness of ciltacabtagene autoleucel in CARTITUDE-1 versus physician's choice of therapy in the Flatiron Health multiple myeloma cohort registry for the treatment of patients with relapsed or refractory multiple myeloma

Thomas Martin; Amrita Krishnan; Kwee Yong; Katja Weisel; Maneesha Mehra; Sandhya Nair; Keqin Qi; Anil Londhe; Joris Diels; Concetta Crivera; Carolyn C Jackson; Yunsi Olyslager; Martin Vogel; Jordan M Schecter; Arnob Banerjee; Satish Valluri; Saad Z Usmani; Jesus G Berdeja; Sundar Jagannath

doi:10.1002/jha2.312

Comparative effectiveness of ciltacabtagene autoleucel in CARTITUDE-1 versus physician's choice of therapy in the Flatiron Health multiple myeloma cohort registry for the treatment of patients with relapsed or refractory multiple myeloma

EJHaem. 2021 Dec 10;3(1):97-108. doi: 10.1002/jha2.312. eCollection 2022 Feb.

Authors

Thomas Martin¹, Amrita Krishnan², Kwee Yong³, Katja Weisel⁴, Maneesha Mehra⁵, Sandhya Nair⁶, Keqin Qi⁷, Anil Londhe⁷, Joris Diels⁶, Concetta Crivera⁸, Carolyn C Jackson⁹, Yunsi Olyslager⁶, Martin Vogel⁵, Jordan M Schecter¹⁰, Arnob Banerjee¹⁰, Satish Valluri⁵, Saad Z Usmani⁹, Jesus G Berdeja¹¹, Sundar Jagannath¹²

Affiliations

¹ UCSF Helen Diller Family Comprehensive Cancer Center San Francisco California USA.
² Judy and Bernard Briskin Center for Multiple Myeloma Research Duarte California USA.
³ University College Hospital London UK.
⁴ University Medical Center Hamburg-Eppendorf Hamburg Germany.
⁵ Janssen Global Services LLC Raritan New Jersey USA.
⁶ Janssen Pharmaceutica NV Beerse Belgium.
⁷ Janssen R&D LLC Titusville New Jersey USA.
⁸ Janssen Scientific Affairs LLC Horsham Pennsylvania USA.
⁹ Levine Cancer Institute-Atrium Health Charlotte North Carolina USA.
¹⁰ Janssen R&D Raritan New Jersey USA.
¹¹ Sarah Cannon Research Institute Nashville Tennessee USA.
¹² Mount Sinai Medical Center New York New York USA.

Abstract

Introduction: Ciltacabtagene autoleucel (cilta-cel) is a novel chimeric antigen receptor T-cell therapy that is being evaluated in the CARTITUDE-1 trial (NCT03548207) in patients with relapsed or refractory multiple myeloma (RRMM) who received as part of their previous therapy an immunomodulatory drug, proteasome inhibitor, and an anti-CD38 monoclonal antibody (i.e., triple-class exposed). Given the absence of a control arm in CARTITUDE-1, this study assessed the comparative effectiveness of cilta-cel and physician's choice of treatment (PCT) using an external real-world control arm from the Flatiron Health multiple myeloma cohort registry.

Methods: Given the availability of individual patient data for cilta-cel from CARTITUDE-1 and PCT in Flatiron, inverse probability of treatment weighting was used to adjust for unbalanced baseline covariates of prognostic significance: refractory status, cytogenetic profile, International Staging System stage, time to progression on last regimen, number of prior lines of therapy, years since diagnosis, and age. Comparative effectiveness was estimated for progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS). A range of sensitivity analyses were conducted.

Results: Baseline characteristics were similar between the two cohorts after propensity score weighting. Patients with cilta-cel had improved PFS (HR: 0.18 [95% CI: 0.12, 0.27; p < 0.0001]), TTNT (HR: 0.15 [95% CI: 0.09, 0.22; p < 0.0001]), and OS (HR: 0.25 [95% CI: 0.13, 0.46; p < 0.0001]) versus PCT. Cilta-cel treatment benefit was robust and consistent across all sensitivity analyses.

Conclusion: Cilta-cel demonstrated significantly superior effectiveness over PCT for all outcomes, highlighting its potential as an effective therapy in patients with triple-class exposed RRMM.

Keywords: CARTITUDE‐1; Flatiron Health; ciltacabtagene autoleucel; indirect treatment comparison; relapsed or refractory multiple myeloma; triple‐class exposed.