Dataset Information

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.

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.

SUBMITTER: Martin T

PROVIDER: S-EPMC9175662 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

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.

Martin Thomas T Krishnan Amrita A Yong Kwee K Weisel Katja K Mehra Maneesha M Nair Sandhya S Qi Keqin K Londhe Anil A Diels Joris J Crivera Concetta C Jackson Carolyn C CC Olyslager Yunsi Y Vogel Martin M Schecter Jordan M JM Banerjee Arnob A Valluri Satish S Usmani Saad Z SZ Berdeja Jesus G JG Jagannath Sundar S

EJHaem 20211210 1

<h4>Introduction</h4>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 ...[more]

PMID: 35846215

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Project description:IntroductionCiltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell therapy approved for patients with relapsed/refractory multiple myeloma (RRMM). In the phase 3 trial, CARTITUDE-4 (NCT04181827), cilta-cel demonstrated improved efficacy vs. standard of care (SOC; daratumumab plus pomalidomide and dexamethasone [DPd] or pomalidomide plus bortezomib and dexamethasone [PVd]) with a ≥ complete response (≥CR) rate of 73.1% vs. 21.8%.MethodsA cost-per-responder model was developed to assess the value of cilta-cel and SOC (87% DPd and 13% PVd) based on the CARTITUDE-4 trial data from a US mixed payer perspective (76.7% commercial, 23.3% Medicare). The model was developed using progression-free survival (PFS), overall survival (OS), and ≥CR endpoints from CARTITUDE-4 over a period of 25.4 months. Inpatient stays, outpatient visits, drug acquisition, administration, and monitoring costs were included. The base-case model assumed an inpatient setting for each cilta-cel infusion; another scenario included 30% outpatient and 70% inpatient infusions. Costs of managing grade 3-4 adverse events (AEs) and grade 1-4 cytokine release syndrome and neurotoxicity were included. Subsequent therapy costs were incurred after disease progression; terminal care costs were considered upon death events. Outcomes included total cost per treated patient, total cost per complete responder, and cost per month in PFS between cilta-cel and SOC. Costs were adjusted to 2024 US dollars.ResultsTotal cost per treated patient, total cost per complete responder, and total cost per month in PFS were estimated at $704,641, $963,941, and $30,978 for cilta-cel, respectively, and $840,730, $3,856,559, and $42,520 for SOC over the 25.4-month period. Cost drivers included treatment acquisition costs before progression and subsequent treatment costs ($451,318 and $111,637 for cilta-cel; $529,795 and $265,167 for SOC). A scenario analysis in which 30% of patients received an outpatient infusion (assuming the same payer mix) showed a lower cost per complete responder for cilta-cel ($956,523) than those with an infusion in the inpatient setting exclusively.DiscussionThis analysis estimated that cost per treated patient, cost per complete responder, and cost per month in PFS for cilta-cel were remarkably lower than for DPd or PVd, highlighting the substantial clinical and economic benefit of cilta-cel for patients with RRMM.

Project description:Background and objectiveCiltacabtagene autoleucel (cilta-cel) is a novel agent being investigated in the single-arm CARTITUDE-1 trial (NCT03548207) for patients with relapsed or refractory multiple myeloma who are triple-class exposed to an immunomodulatory drug, proteasome inhibitor, and an anti-CD38 monoclonal antibody. The objective of this study was to evaluate the comparative efficacy of cilta-cel vs physician's choice of treatment, as no head-to-head trials have been conducted.MethodsAn external control arm for CARTITUDE-1 was created from patients in the long-term follow-up for three clinical trials of daratumumab (POLLUX, CASTOR, and EQUULEUS) who satisfied the eligibility criteria of CARTITUDE-1. These patients received physician's choice of treatment following the discontinuation of study drugs. Inverse probability of treatment weighting was used to align the external control and CARTITUDE-1 populations on important baseline characteristics. Overall response rate, complete response or better rate, progression-free survival, time to next treatment, and overall survival were assessed. Several sensitivity analyses were conducted.ResultsAfter propensity score weighting, baseline characteristics were comparable between cohorts. Patients showed improved results with cilta-cel vs physician's choice of treatment: overall response rate (relative risk: 2.95 [95% confidence interval (CI) 2.27, 3.84; p < 0.0001]), complete response or better (relative risk: 111.70 [95% CI 29.08, 429.06; p < 0.0001]), progression-free survival (hazard ratio [HR]: 0.24 [95% CI 0.15, 0.37; p < 0.0001]), time to next treatment (HR: 0.14 [95% CI 0.09, 0.22; p < 0.0001]), and overall survival (HR: 0.21 [95% CI 0.13, 0.35; p < 0.0001]). Results were consistent across all sensitivity analyses.ConclusionsCilta-cel showed superior efficacy compared with physician's choice of treatment, making it a promising new treatment option for patients with triple-class exposed relapsed or refractory multiple myeloma.

Project description:IntroductionChimeric antigen receptor (CAR) T-cell therapy (CAR T therapy) is a treatment option for patients with relapsed or refractory multiple myeloma that has led to unprecedented treatment outcomes. Among CAR T therapies available, ciltacabtagene autoleucel (cilta-cel) is a good candidate for outpatient administration due to its generally predictable safety profile. There are multiple advantages of outpatient administration of cilta-cel, including reduced healthcare burden, expanded access, and patient autonomy. This mixed methods qualitative study aimed to identify key factors for outpatient administration of CAR T and best practice recommendations by combining a targeted literature review with expert interviews and panels.MethodsThe targeted review (Phase 1) aimed to identify factors for outpatient CAR T administration in the US and determine key topics for the exploratory interviews (Phase 2) and expert panels (Phase 3), which aimed to inform on best practices and challenges of outpatient CAR T administration (focusing on cilta-cel). Participants in clinical and administrative positions based in treatment centers that had experience with real-world outpatient administration of cilta-cel were recruited.ResultsSeventeen studies were identified in Phase 1. Key factors for outpatient administration included the development of protocols for CAR T complications, education for caregivers, outpatient specialists, hospital staff, and emergency services staff for identification and referral after possible adverse events, the creation of multidisciplinary teams for effective communication and management, straightforward patient intake processes encompassing financial eligibility review and provision of patient education materials, and close patient monitoring throughout the treatment journey. In Phase 2, 5 participants from 2 centers were interviewed. In Phase 3, 14 participants across 6 treatment centers were interviewed. Two 90-minute virtual panel discussions took place. All participants agreed that cilta-cel can be safely and effectively administered in an outpatient setting. Key recommendations included the creation of educational resources for patients and caregivers, the development of standard operating procedures, dedicated outpatient infrastructure and establishment of interdisciplinary teams, outpatient monitoring for toxicity management, and monitoring of the reimbursement landscape.DiscussionThis study offers a comprehensive understanding of the feasibility of outpatient cilta-cel administration in participating CAR T centers and provides actionable recommendations while acknowledging existing challenges.

Dataset Information

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.

Introduction

Methods

Results

Conclusion

Publications

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.

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