Mara-Victoria Mateos earned her medical degree from the University of Valladolid in Spain and finished her hematological residency at the Salamanca University Hospital, where she also earned her doctorate . Dr. Mateos is currently an Associate Professor of Psychology. In this video Dr. Mateos discusses the 550 Ciltacabtagene Autoleucel for Triple-Class Exposed Multiple Myeloma
Link to Abstract:
https://ash.confex.com/ash/2021/webprogram/Paper146200.html
Abstract:
Patients with relapsed and refractory multiple myeloma (RRMM) who have been exposed to immunomodulatory medicines (IMiDs), proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies (MoABs) in the triple class have a poor prognosis and a large unmet medical need. Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell treatment that may provide these individuals with long-term illness management. CARTITUDE-1 is a phase 1b/2 open-label, single-arm clinical trial that aims to determine the safety and efficacy of cilta-cel in adult patients with triple-class exposed RRMM. Because CARTITUDE-1 is a single-arm research, adjusted comparisons to other already available medicines can give useful information on cilta-relative cel’s effectiveness and safety advantages over current clinical practice (RWCP). The first prospective research of RWCP effectiveness and safety in triple-class exposed patients with RRMM is LocoMMotion. It was created with the intention of serving as an external control cohort for CARTITUDE-1, with aligned inclusion criteria and endpoint definitions to allow for robust, high-quality indirect comparisons against cilta-cel.
In patients with triple-class exposed RRMM, compare patient outcomes of cilta-cel vs. RWCP, including overall response rate (ORR), complete response or better rate (CR rate), progression-free survival (PFS) as determined by a review committee, and overall survival (OS).
To conduct the comparison analysis, individual patient level data from both CARTITUDE-1 (clinical cut-off February 2021) and LocoMMotion (clinical cut-off March 2021) were merged. Inverse probability weighting was used to correct for imbalances between the two cohorts on key prognostic baseline characteristics such as refractory status, ISS stage, time to progression on prior line, number of prior lines, average duration of prior lines, age, creatinine clearance, ECOG PS, and MM type. The weighted RWCP cohort was created by applying average treatment effect on the treated (ATT) weights derived from propensity scores estimated using multivariable logistic regression modeling to the LocoMMotion patients, resulting in a weighted RWCP cohort that reflected the CARTITUDE-1 patient population. Reduced normalized mean differences and overlap of propensity score distributions were used to assess the balance between the ATT weighted RWCP cohort and the CARTITUDE-1 population. The relative treatment effects of cilta-cel vs. RWCP on binary endpoints (Odds ratios (OR), translated into Response-rate Ratios (RR) and time to event endpoints (Hazard ratios (HR)) were estimated using weighted logistic and Cox proportional hazards regression, respectively. All enrolled (apheresed) patients from CARTITUDE-1 were included in the base case analysis, showing an intention to treat approach. Additional analyses were performed with just patients who received cilta-cel infusion compared to a LocoMMotion aligned population with patients who progressed or died within 52 days being eliminated from the LocoMMotion cohort.
CARTITUDE-1 enrolled 113 patients, with 97 of them receiving cilta-cel treatment. 246 patients were enrolled in LocoMMotion receiving RWCP in Italy (24%), Germany (15%), France (14%), the United Kingdom (11%), Spain (10%), the United States (9%), Belgium (5%), Poland (5%), the Netherlands (4%), and Russia (4%). (3 percent ). The RWCP group received a wide range of treatments, with over 90 different therapy regimens being employed. Kd (13.8 percent), PCd (12.6 percent), and Pd were the most popular regimens (11.0 percent ). With the CARTITUDE-1 cohort, the weighted LocoMMotion population was well balanced. For ORR (RR=4.43), CR (RR=568.92), PFS (HR=0.15), and OS (HR=0.38), adjusted comparisons (Table 1) revealed statistically significant benefits for cilta-cel vs. RWCP, all with p0.001. All subsequent analyses corroborated these findings (Table 1).
Conclusions: In LocoMMotion, the outcomes for patients with triple-class exposed RRMM treated with RWPC were dismal, demonstrating the large unmet medical need. When compared to a varied group of RWCP, cilta-cel has dramatically improved ORR, CR, PFS, and OS when compared to CARTITUDE-1. These findings point to cilta-potential cel’s as a highly successful treatment for triple-class exposed RRMM patients.