CAR T Therapy Shows Similar Efficacy, Safety in Multiple Myeloma Subgroups

"Close monitoring may be warranted for patients with baseline [renal impairment] as they may experience more pronounced ICANS and infection rates," according to the study authors.

BCMA-targeting CAR T-cell therapies conferred higher rates of infection and immune effector cell-associated neurotoxicity (ICANS) with comparable progression-free survival (PFS) and overall survival (OS) outcomes among patients with relapsed/refractory multiple myeloma and baseline renal impairment, according to findings from a real-world analysis.1

Between patients with normal renal function and those with baseline renal impairment, investigators observed similar response rates with CAR T-cell therapy at 1 month (P = .088), 3 months (P > .9), and 6 months (P = .8). After a median follow-up of 27.9 months (IQR, 11-not available [NA]), the median PFS was 21.9 months vs 15.0 months in each respective population (P = .319). Additionally, the median OS was not reached and 27.9 months, respectively (P = .872).

In the overall population (n = 223), patients with normal renal function (n = 198), and those with baseline renal impairment (n = 25), respectively, any-grade cytokine release syndrome (CRS) affected 82%, 80%, and 96% (P = .055). Most patients in each respective population experienced maximum grade 1 CRS (58% vs 58% vs 56%; P = .065).

ICANS occurred in 21%, 19%, and 36% of the overall population, patients with normal renal function, and those with baseline renal impairment, respectively (P = .044). Most instances of ICANS were maximum grade 1 in each group (12% vs 11% vs 20%; P = .023).

Investigators reported acute infections in 23% of the overall population, 20% of those with normal renal function, and 44% of patients with baseline renal impairment (44%; P = .008). The median duration of hospitalization was 10 days (range, 7-15), 10 days (range, 7-15), and 10 days (range, 8-15), respectively (P >.9).

“Patients with [relapsed/refractory multiple myeloma] and baseline [renal impairment] exhibited increased rates of ICANS and infection, yet PFS, OS, and other toxicity profiles, including rates of cytopenia at 30, 60, and 90 days showed no significant differences between the subgroups,” Alma Habib, MD, of The Ohio State University and the US Myeloma Innovations Research Collaborative (USMIRC), wrote with study coauthors.1 “This experience underscores the comparable efficacy and safety of BCMA [CAR T-cell therapy] in patients with [relapsed/refractory multiple myeloma] and baseline [renal impairment]. Close monitoring may be warranted for patients with baseline [renal impairment] as they may experience more pronounced ICANS and infection rates.”

According to the investigators, BCMA-directed agents such as ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma)–which were first approved by the FDA for previously treated multiple myeloma in February 20222 and March 20213, respectively—have demonstrated promising outcomes among patients. However, they noted limited real-world evidence related to the efficacy and safety of CAR T-cell therapy among patients with baseline renal impairment. Investigators of this multicenter, retrospective study assessed the tolerability and activity of BCMA-targeting CAR T-cell therapy in those with relapsed/refractory multiple myeloma and renal impairment at baseline.

The study evaluated patients with relapsed/refractory multiple myeloma who received treatment with cilta-cel or ide-cel from May 2021 to April 2024. Investigators collected data on patients and outcomes from multiple US academic institutions that have worked with the USMIRC.

Investigators defined renal impairment as having a creatinine clearance of less than 45 ml per minute. Patient responses were determined via International Myeloma Working Group guidelines, with toxicities being assessed using CTCAE v5.0 criteria. Analysis of contingency tables involved the use of Fisher’s exact test, while investigators employed Kaplan-Meier methods to calculate PFS and OS outcomes.

The mean age was 64.0 years in the overall population, 63.8 years (range, 34-84) in the normal renal function subgroup, and 66.3 years (range, 50-80) in the baseline renal impairment subgroup. Most patients were male in the overall and normal renal function groups (56% vs 59%), while a majority of those with baseline renal impairment were women (68%).

Most patients in the overall population, normal renal function group, and renal impairment group, respectively, had heavy isotope IgG (60% vs 62% vs 44%) and light chain kappa (61% vs 62% vs 48%). Extramedullary disease was noted in 37%, 38%, and 32% of patients in each group.

Investigators presented these findings in a poster session at the 2024 American Society of Hematology Annual Meeting & Exposition (ASH).

References

1. Habib A, Ahmed N, Khan A, et al. A real-world analysis of the safety and efficacy of BCMA-directed CAR T-cell therapy for patients with relapsed/refractory multiple myeloma and baseline renal impairment. Blood. 2024;144(suppl 1):2009. doi:10.1182/blood-2024-208799
2. FDA approves ciltacabtagene autoleucel for relapsed or refractory multiple myeloma. News release. FDA. February 28, 2022. Accessed January 23, 2025. https://tinyurl.com/4h785f67
3. FDA approves idecabtagene vicleucel for multiple myeloma. News release. FDA. March 26, 2021. Accessed January 23, 2025. https://bit.ly/40HDFgj