Adjusted comparison of outcomes between patients from CARTITUDE-1 versus multiple myeloma patients with prior exposure to proteasome inhibitors, immunomodulatory drugs and anti-CD38 antibody from the prospective, multinational LocoMMotion study of real-world clinical practice

Abstract

Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell therapy studied in patients with multiple myeloma exposed to three classes of treatment in the single-arm CARTITUDE-1 study. To assess the effectiveness of cilta-cel compared to real-world clinical practice (RWCP), we performed adjusted comparisons using individual patients' data from CARTITUDE-1 and LocoMMotion, a prospective, multinational study of patients with multiple myeloma triple-class exposed of treatment. Comparisons were performed using inverse probability weighting. In CARTITUDE-1, 113 patients were enrolled, and 97 patients were infused with cilta-cel. In LocoMMotion, 248 patients were enrolled, and 170 patients were included in the comparisons versus infused patients. Ninety-two unique regimens were used in LocoMMotion, most frequently carfilzomib-dexamethasone (13.7%), pomalidomide-cyclophosphamide-dexamethasone (13.3%) and pomalidomidedexamethasone (11.3%). Adjusted comparisons showed that patients treated with cilta-cel were 3.12-fold more likely to respond to treatment than those managed by RWCP (response rate, 3.12, 95% confidence interval [95% CI]: 2.24-4.00), had their risk of progression or death reduced to by 85% (progression-free survival hazard ratio=0.15, 95% CI: 0.08-0.29), and a risk of death lowered by 80% (overall survival hazard ratio HR=0.20, 95% CI: 0.09-0.41). The incremental improvement in healthrelated quality of life from baseline for cilta-cel versus RWCP at week 52, as measured by EORTC QLQ-C30 Global Health Status, was 13.4 (95% CI: 3.5-23.6) and increased to 30.8 (95% CI: 21.8-39.8) when including death as additional information regarding patients' health status. Patients treated with cilta-cel experienced more adverse events than those managed with RWCP (any grade: 100% vs. 83.5%). The results from this study demonstrate improved efficacy outcomes of cilta-cel versus RWCP and highlight its potential as a novel and effective treatment option for patients with multiple myeloma triple-class exposed of antimyeloma treatment. CARTITUDE-1 is registered with clinicaltrials gov. Identifier: NCT03548207. LocoMMotion is registered with clinicaltrials gov. Identifier: NCT04035226.

Figure 1.

Selection of patients for the CARTITUDE-1 and LocoMMotion populations. Patients in CARTITUDE-1 were treated with ciltacabtagene autoleucel, patients in the LocoMMotion study were treated with real-world clinical practice.

Figure 2.

Unadjusted and adjusted Kaplan-Meier survival curves for the infused/aligned population. (A) Progression-free survival. (B) Overall survival. Blue lines represent the survival of patients treated with ciltacabtagene autoleucel, the solid red lines represent the unadjusted survival of patients treated with real-world clinical practice (RMCP) and the dotted orange lines are adjusted Kaplan-Meier curves following inverse probability weighting. Cilta-cel: ciltacabtagene autoleucel; ATT: average treatment effect in the treated population; HR: hazard ratio.

Figure 3.

Summary of unadjusted and adjusted comparisons for response and survival outcomes. (A) Forest plots of response outcomes showing response ratios with corresponding 95% confidence intervals (95% CI) comparing ciltacabtagene autoleucel (cilta-cel) versus real-world clinical practice (RWCP) with different analytical methods and for the infused/aligned and enrolled patient populations. Values >1 favor cilta-cel, values <1 favor RWCP. (B) Forest plots of survival outcomes showing hazard ratios (HR) with corresponding 95% confidence intervals comparing cilta-cel versus RWCP with different analytical methods and for the infused/aligned and enrolled patient populations. Values <1 favor cilta-cel, values >1 favor RWCP. RR: response rate ratio; ORR: overall response rate; IPW: inverse probability weighting; ATT: average treatment effect in the treated population; ATO: average treatment effect in the overlap population; VGPR: very good partial response; RWCP: real-world clinical practice; OS: overall survival; PFS: progression-free survival.

Figure 4.

Comparisons of patient-reported outcomes. (A) Comparison of EuroQoL Group’s EQ visual analog scale (EQ VAS) of patients who were alive and did not initiate subsequent therapy. (B) Comparison of EORTC QLQ-C30 global health status (GHS) of patients who were alive and did not initiate subsequent therapy. (C) Comparison of EQ VAS of patients who were alive and did not initiate subsequent therapy or died, i.e., adjusted for informative dropout analysis. (D) Comparison of EORTC QLQ-C30 GHS of patients who were alive and did not initiate subsequent therapy or died, i.e., adjusted for informative dropout analysis; ciltacel: ciltacabtagene autoleucel; RWCP: real-world clinical practice.