Real-World Data of SOC Cilta-Cel in R/R MM and Cilta-Cel in Patients With High-Risk Features

Opinion
Video

Panelists discuss real-world evidence showing that chimeric antigen receptor (CAR) T-cell therapy is safe and effective in traditionally excluded populations with multiple myeloma, including those with comorbidities or central nervous system (CNS) involvement, emphasizing the role of multidisciplinary care, proactive toxicity management, and growing confidence in extending access to high-risk patients.

Recent real-world studies have expanded our understanding of CAR T-cell therapy’s safety and efficacy in populations historically excluded from clinical trials. Patients with renal dysfunction, poor performance status, or other comorbidities have been shown to tolerate CAR T-cell therapy well, with outcomes comparable to those seen in trial-eligible individuals. Notably, the lymphodepleting regimen used before CAR T is relatively mild, making it feasible even for those with compromised organ function. The use of multidisciplinary care teams—such as cardiology, neurology, and infectious disease—has further enhanced safety by addressing specific risks up front.

Delayed neurologic toxicities remain an important consideration, with approximately 10% of patients experiencing non–immune effector cell–associated neurotoxicity syndrome (ICANS) neurotoxicities in real-world cohorts. Although parkinsonism and cranial nerve palsies were observed, the severity and frequency were generally lower than in earlier trials. Strategies such as disease debulking before infusion and the use of steroids to manage elevated lymphocyte counts are being explored to mitigate risk. Importantly, the rates of severe cytokine release syndrome and ICANS remain low, and infections remain the most common cause of nonrelapse mortality. As a result, many centers now provide prophylactic interventions such as intravenous immunoglobulin and antibiotics, along with structured posttreatment monitoring.

Expanding CAR T access to high-risk groups such as those with CNS myeloma or plasma cell leukemia (PCL) is also gaining traction. Preliminary data suggest that CNS involvement does not significantly increase neurotoxicity risk when patients are pretreated with CNS-directed therapies. Some have even achieved complete CNS responses without added complications. Similarly, patients with PCL have demonstrated meaningful responses. These findings reflect a growing confidence in safely delivering CAR T-cell therapy to patients in urgent need, driven by a deeper understanding of toxicity management and the collaborative efforts of clinical consortiums collecting real-world data.

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