# Real-World Experience with Approved CAR T-Cell Therapies Ciltacabtagene Autoleucel and Idecabtagene Vicleucel in 1272 Relapsed/Refractory Multiple Myeloma Patients

## TL;DR

This study shows that CAR T-cell therapies cilta-cel and ide-cel are effective in treating multiple myeloma patients in real-world settings, with high survival rates and manageable side effects.

## Contribution

The study provides real-world evidence of CAR T-cell therapy effectiveness and safety in a large, diverse patient population.

## Key findings

- One-year survival rates were approximately 90% for cilta-cel and 75% for ide-cel.
- Baseline renal impairment was linked to worse survival outcomes, while prior anti-CD38 antibody use did not affect survival.
- Severe hematologic toxicity and immunosuppressive effects were common but severe events like ICANS were rare.

## Abstract

Multiple myeloma is a type of blood cancer that remains difficult to treat when it returns after treatment. Recently, advanced therapies called CAR T-cells have gained approval, but data on their use in everyday clinical practice is limited. This study analyzed real-world data from 1272 patients treated with the two approved CAR T-cell products (cilta-cel and ide-cel). The one-year survival rates were approximately 90% for cilta-cel and 75% for ide-cel. Notably, prior exposure to anti-CD38 antibodies—now a standard in the frontline setting—did not significantly impact survival outcomes. Conversely, baseline renal impairment was associated with significantly inferior survival. While any-grade CRS and ICANS were observed in approximately 42–46% and 12–15% of patients, respectively, severe events remained rare (<3%). High rates of severe low blood counts and infections were prevalent, highlighting a significant immunosuppressive burden. These findings confirm that CAR T-cell therapies are effective and feasible in diverse real-world populations.

Background: Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) have transformed the treatment landscape of relapsed/refractory multiple myeloma (RRMM). Given their recent regulatory approval and limited availability, mainly due to logistical issues, real-world data remain scarce. Methods: A retrospective study was conducted using the TriNetX database, identifying adult patients with RRMM treated with either cilta-cel or ide-cel. The clinical outcomes evaluated included overall survival (OS), progression-free survival (PFS), as well as the safety profile. Results: A total of 697 patients treated with cilta-cel and 575 with ide-cel were identified. The median age was 65 and 67 years, with ~16% being Black/African American. The 12-month OS was 89.6% for cilta-cel and 86.0% for ide-cel. In a descriptive subgroup analysis, renal impairment (eGFR < 60 mL/min/1.73 m2) seemed to be associated with significantly inferior OS in both cohorts (HR = 3.66, p < 0.001 for cilta-cel; HR = 1.73, p = 0.003 for ide-cel). Conversely, prior anti-CD38 exposure did not seem to impact survival in any of the two treatment groups. Any-grade CRS occurred in 45.9% (cilta-cel) and 41.8% (ide-cel), while any-grade ICANS was observed in 15.4% and 11.8%, respectively. Severe (grade ≥ 3) ICANS remained rare (<3%) in both cohorts. Hematologic toxicity was prevalent, with grade ≥ 3 neutropenia occurring in 76.0% (cilta-cel) and 68.0% (ide-cel). Notably, any-grade infections (28.5–40.1%) and hypogammaglobulinemia (41.1–43.1%) were frequent, highlighting a significant long-term immunosuppressive burden. Conclusions: In these real-world cohorts, both approved CAR T-cell therapies demonstrated favorable survival outcomes. While the incidence of severe hematologic and immune-related toxicities was high, these findings are compatible with published data from clinical trials and it seems that the clinical utility of these drugs overcomes the adverse safety profile.