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

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  1 , Amrita Krishnan  2 , Kwee Yong  3 , Katja Weisel  4 , Maneesha Mehra  5 , Sandhya Nair  6 , Keqin Qi  7 , Anil Londhe  7 , Joris Diels  6 , Concetta Crivera  8 , Carolyn C Jackson  9 , Yunsi Olyslager  6 , Martin Vogel  5 , Jordan M Schecter  10 , Arnob Banerjee  10 , Satish Valluri  5 , Saad Z Usmani  9 , Jesus G Berdeja  11 , Sundar Jagannath  12
Affiliations

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 et al. EJHaem. .

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.

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Conflict of interest statement

KW received honoraria from and served in a consulting or advisory role for Adaptive Biotechonlogies, Amgen, BMS, Celgene, GSK, Janssen, KaryopharmTherapeutics, Oncopeptides, Roche/Genentech, Sanofi, and Takeda, served in a consulting or advisory role for GSK, received travel funding from Amgen, BMS, Celgene, GSK, Janssen, and Takeda, and received research funding from Amgen, Celgene, Janssen, and Sanofi.TM served in a consulting or advisory role for GlaxoSmithKline and Juno Therapeutics, and received research funding from Amgen, Janssen, and Sanofi.AK served in a consulting or advisory role for Adaptive Biotechnologies, Celgene/Bristol Meyers‐Squibb, GlaxoSmithKline, Janssen Oncology, Pfizer, Regeneron, served on speakers bureaus for Amgen, Celgene/Bristol Meyers‐Squibb, GlaxoSmithKline and Takeda, served on scientific advisory boards for Sutro Biopharma, has equity in Celgene/Bristol Meyers‐Squibb, and received research funding from Janssen Oncology.SJ is a consultant for Bristol Myers Squibb, Janssen, Karyopharm Therapeutics, Merck, Sanofi, and Takeda Pharmaceuticals.SZU served in a consulting or advisory role for AbbVie, Amgen, Celgene, GlaxoSmithKline, Janssen, Karyopharm Therapeutics, Merck, Seattle Genetics, Skyline Diagnostics, and Takeda, served on speakers bureaus for Celgene, Janssen, Sanofi, and Takeda, and received research funding from Amgen, Array BioPharma, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, and Skyline Diagnostics.JGB served in a consulting or advisory role for Bluebird Bio, Bristol Myers Squibb, Celgene, CRISPR Therapeutics, Janssen, Karyopharm Therapeutics, Kite/Gilead, Legend Biotech, Secura Bio, Servier, and Takeda, and received research funding from AbbVie, Acetylon Pharmaceuticals, Amgen, Bluebird Bio, Bristol Myers Squibb, Celgene, Celularity, Constellation Pharmaceuticals, CURIS, EMD Serono, Genentech/Roche, Glenmark, Ichnos Sciences, Janssen, Kesios Therapeutics, Lilly, Novartis, Poseida, Sanofi, Takeda, Teva, and Vivolux.KY is consultant physician and received honoraria from Janssen, GSK, Amgen Inc., Takeda, Sanofi and research funding from Janssen, Takeda, Sanofi.AL, CC, JMS, KQ, MV, AB, JD, SN, SV, and YO are employed by Janssen and have restricted stock units and/or stock options. CCJ is employed by Janssen and is a consultant physician at the Memorial Sloan Kettering Cancer Center. MM was employed by Janssen when the study was conducted.

Figures

FIGURE 1
FIGURE 1
Flow chart of patient selection [1]. CARTITUDE‐1 inclusion criteria required at least three prior LOTs or double refractoriness to an immunomodulatory drug and a proteasome inhibitor; however, all enrolled patients received at least three prior LOTs [2]. CARTITUDE‐1 inclusion criterion was creatinine clearance of ≥40 mL/min/1.73 m2; however, all enrolled patients had creatine levels ≤ 2 mg/dL. Abbreviations: ECOG, Eastern Cooperative Oncology Group; LOT, line of therapy; MM, multiple myeloma; N OBS, number of observations; RW, real world
FIGURE 2
FIGURE 2
Kaplan–Meier plots for (A) progression‐free survival, (B) time to next treatment, and (C) overall survival in CARTITUDE‐1 (observed) and the RW cohort (observed and adjusted). Note: Number at risk for the adjusted RW cohort represents the sum of the propensity score weights, not the effective sample size. Adjusted results correspond to the base case analysis which adjusted for refractory status, International Staging System stage, cytogenetic profile, time to progression on last regimen, number of prior lines of therapy, years since multiple myeloma diagnosis, and age. The adjusted curves reflect inverse probability of treatment weighting with average treatment effect in the treated weights (not doubly robust). Abbreviation: RW, real world
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