Real-World Tolerability of Cilta-Cel Aligns With Multiple Myeloma Trials

Doris K. Hansen, MD, of Moffitt Cancer Center, discusses data from a Center for International Blood and Marrow Transplant Research retrospective registry study evaluating ciltacabtagene autoleucel (Carvykti; cilta-cel) in a real-world setting. Enrolling 595 patients, this investigation represents the largest real-world cohort of cilta-cel–treated patients with multiple myeloma evaluated to date. At a median follow-up of approximately 1 year, the chimeric antigen receptor (CAR) T-cell therapy demonstrated highly favorable clinical activity in an older, heavily pretreated patient population characterized by a significant burden of baseline comorbidities.

The real-world cohort demonstrated robust efficacy, achieving a best overall response rate of approximately 87%. Furthermore, a deep response of a very good partial response or better was observed in approximately 75% of the study population. Follow-up revealed a 12-month progression-free survival (PFS) rate of 73% and a 12-month overall survival rate of 85%. Although Hansen emphasizes that longer-term follow-up remains necessary to confirm survival durability, these initial data points validate cilta-cel’s therapeutic efficacy outside the strict confines of a clinical trial.

From a safety and tolerability perspective, the real-world toxicity profile closely mirrored historical clinical trial data. Cytokine release syndrome occurred in a majority of patients (80%), but grade 3 or higher events were limited to just 4%. Similarly, immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 22% of the cohort, with only 4% manifesting as high grade.

A key focus of the analysis centered on delayed, non-ICANS neurologic toxicities (NINTs), which present a significant concern in clinical practice. The overall rate of NINTs was 5%, consisting of parkinsonism (2.7%) and cranial nerve palsies (2.5%), which predominantly manifested as cranial nerve 7 palsies. Crucially, the treatment-related mortality rate stood at approximately 5%. This mortality threshold aligns with historical trial data and trends slightly lower than rates reported in alternative real-world tracking studies, providing strong clinical reassurance regarding the safety of cilta-cel delivery.