Ciloleucel

Ciloleucel is a chimeric antigen receptor (CAR) T-cell therapy directed against B-cell maturation antigen (BCMA) and is used in the treatment of multiple myeloma. It is an autologous cellular therapy, meaning a patient’s own T cells are collected, genetically modified to express a BCMA-targeted CAR, expanded, and then reinfused after a lymphodepleting chemotherapy regimen.

Mechanism and administration: In ciloleucel, the engineered T cells are designed to recognize BCMA on myeloma cells and mount an immune response to attack them. After a patient undergoes leukapheresis, the T cells are processed in a manufacturing facility and returned to the patient via infusion. Prior to infusion, patients typically receive lymphodepleting therapy (often cyclophosphamide and fludarabine). The treatment is administered at specialized centers equipped to monitor for and manage potential toxicities. The manufacturing process can take several weeks and requires careful coordination for timely delivery.

Clinical use and evidence: Ciloleucel has been studied in adults with relapsed or refractory multiple myeloma and has shown promising activity in clinical trials, with substantial response rates and deep responses in patients who have received multiple prior therapies. Regulatory approvals have been granted in several regions for adults with multiple myeloma who have received extensive prior treatment, reflecting its role as a therapy for advanced disease after other options have been exhausted. Ongoing studies continue to evaluate its long-term efficacy and safety.

Safety and monitoring: The most notable risks include cytokine release syndrome and neurologic toxicities, along with cytopenias, infections, and hypogammaglobulinemia. Management typically involves close inpatient or specialized center monitoring, with interventions such as tocilizumab for CRS and corticosteroids for severe neurotoxicity. Patient selection, careful monitoring, and post-infusion follow-up are essential components of care.