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.

Real-world Treatment Patterns and Clinical Outcomes for Metastatic Renal Cell Carcinoma in the Current Treatment Era

“…TTNT was defined as the time between the index date and initiation of the next treatment or death, whichever occurred first. If none of these criteria were met, patients were censored at the last visit date or the study end date [11] , [16] . OS was defined as the time from the index date to date of death.…”

Ciltacabtagene Autoleucel for Patients With Triple-class Exposed Multiple Myeloma: Adjusted Comparison of CARTITUDE-1 Patient Outcomes Versus Real-world Clinical Practice

“…These results provide compelling evidence regarding the benefits of cilta-cel for the treatment of TCE RRMM patients and align with other recent analyses involving externally derived controls for CARTITUDE-1 from different countries, despite variability in the RWCP regimens. 9–14 The current study demonstrated important gains with cilta-cel compared to RWCP for ORR, ≥VGPR, PFS, TTNT, and OS. Patients treated with cilta-cel are 3.0 and 11.5 times more likely to reach ORR and ≥VGPR, respectively, and had substantial improvements in PFS (by 88%), TTNT (by 89%), and OS (by 87%).…”

Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials

“…We retrieved 3133 unique records, of which 200 were included in the review (Figure 1). All reasons for excluding records after full-text review are given in eAppendix 6 in Supplement 1.…”

“…One-hundred and fifteen studies (58%) completely reported how the target trial protocol was emulated. Eighty-seven studies (44%) provided both the protocol of the target trial and described how it was emulated (Table 2).…”

“…Seventy studies (35%) reported in the title that the study aimed to emulate a target trial; 180 (90%) did so in the Methods section. Twenty studies (10%) reported the study was prospectively registered, 16 of these 20 (80%)…”