Ciltacabtagene Autoleucel Demonstrates Efficacy for Patients With R/R Multiple Myeloma in Real-World Population
Among patients with relapsed/refractory (R/R) multiple myeloma (MM), treatment with ciltacabtagene autoleucel (cilta-cel) demonstrated feasibility and efficacy in a real-world setting, according to study results published in Blood.
Previous research has found the B-cell maturation antigen- targeting chimeric antigen receptor (CAR) T-cell, cilta-cel, is safe and efficacious in clinical trial populations which have strict eligibility criteria. To expand on these results, researchers conducted a multicenter retrospective study in a real-world population.
Eligible patients with R/R MM who underwent leukapheresis for commercial cilta-cel manufacturing from March 2022 to December 2022 were included and treated with cilta-cel or a nonconforming CAR T-cell product at 16 medical centers in the US. Overall survival (OS) was determined as the time between the date of CAR T-cell infusion and date of death from any cause. Additionally, progression-free survival (PFS) was determined as time between the date of CAR T-cell infusion and date of progression or death.
Apheresis was undergone by 255 patients and 236 received an infusion. Failure to receive an infusion among patients included disease progression/death prior to infusion (n = 13), manufacturing failure (n = 3), myelodysplastic syndrome development (n=1), lung cancer development (n = 1), and loss to follow up (n = 1). Patients who did not receive an infusion received a nonconforming product (n = 19). Approximately 81% (n=191) were infused with Flu/Cy, 13% (n = 31) were infused with bendamustine, 3% (6) with cladribine and cyclophosphamide, and 3% (n = 7) with cyclophosphamide only.
Overall, the median age of patients was 64 years, majority of which were white (76%), high-risk cytogenetics were found in 39% of patients, and 26% had extramedullary disease (EMD). Notably, 54% of patients were not previously eligible for clinical trials of cilta-cel for R/R MM, and the median lines of prior therapy was 6.
As for treatment-related adverse events, cytokine release syndrome (CRS) was found in 75% of patients who received an infusion, of which 5% were grade 3 or higher, ICANS was seen in 14% of which 4% was grade 3 or higher, and 10% of patients experienced delayed neurotoxicity (DNT). About 47% of patients had infections, of which 46% were severe. Cytopenias of grade 3 or higher were experienced by 70% of patients by day 30, while 59% had neutropenia and 49% had thrombocytopenia. About 8.5% of patients had second primary malignancies (SPMs) after infusion. By last follow-up, 50 patients died with 23 due to infections, CRS, DNT, SPMs, ICANS, and immune effector cell-associated hemophagocytic lymphhistiocytosis-like syndrome.
Among the entire study population, overall response rate (ORR) was 84% with a complete response (CR) rate of 66%. In patients who received cilta-cel infusions, the ORR was 89% and the CRR rate was 70%. The median PFS or OS at 13 months follow-up was not reached by any patient.
“This large, multicenter, real-world evidence study is, to our knowledge, the first to report on outcomes in patients, with R/R MM receiving SOC [standard-of-care] cilta-cel,” the researchers concluded, “our data indicate that cilta-cel administration in the real world is feasible and effective, although there is a need for better toxicity management.”
Source:
Sidana S, Patel KK, Peres LC, et al. Safety and Efficacy of Standard of Care Ciltacabtagene Autoleucel for Relapsed/Refractory Multiple Myeloma. Blood. Published online: January 2, 2025. doi: 10.1182/blood.2024025945
