This article presents real-world data on the efficacy of Bristol Myers Squibb and 2seventy bio's idecabtagene vicleucel (ide-cel, marketed as Abecma) in treating patients with relapsed/refractory (r/r) multiple myeloma (MM) affecting the central nervous system (CNS). Presented in a poster at the 66th American Society of Hematology (ASH) Annual Meeting in San Diego, California from December 7-10, 2024, the data offers valuable insights into the treatment approach for this rare form of the disease. Unlocking the Potential of CAR-T Therapy in CNS-Involved MM
Overview of the Study
A multicenter retrospective study involving 153 patients treated with ide-cel at 7 tertiary care centers in Germany and Switzerland between March 2022 and May 2024 was conducted. Among them, 10 patients with confirmed CNS myeloma were analyzed in detail. These patients had a median age of 61 years, with 60% having leptomeningeal sites and 20% having central nerve lesions. All had neurological symptoms and had received between 1 and 7 therapies before the development of CNS myeloma.The FDA's approvals of ide-cel and other CAR-T therapies were based on clinical trials that excluded patients with CNS disease, so existing data on the efficacy of CAR-T in such patients is limited. This study aimed to fill this gap and provide valuable information for the treatment of MM with significant CNS manifestation. 2: The study also compared patients with unconfirmed CNS myeloma with those in the ide-cel treated population without CNS manifestations. Matched based on various factors, the results showed similar median progression-free survival (PFS) and overall survival (OS) between the two cohorts, indicating the potential effectiveness of ide-cel in both cases.
Response to Ide-cel Treatment
Before ide-cel treatment, the best serologic response was complete response (CR) in 50%, partial response (PR) or very good partial response (VGPR) in 40%, and progressive disease (PD) in 10%. At ide-cel infusion, the serologic response was CR in 40%, PR or VGPR in 40%, stable disease in 10%, and unknown in 10%. After ide-cel treatment, the best serologic response was CR in 50% and PR in 50%. 2: As of the last follow-up, 40% had relapse of MM after ide-cel, while 40% were in serologic CR and 20% in PR. Six patients remained alive, demonstrating the complex nature of the treatment response and the need for further research.
Immune-Related Effects
Some patients experienced immune effector-cell associated neurotoxicity syndrome, but none had grade 2 or higher. Cytokine release syndrome (CRS) of grade 2 or 3 was reported in 6 patients, but none had grade 4 CRS. These findings suggest that while there are some immune-related side effects, they are generally manageable. 2: The presence of CAR T-cells in the cerebrospinal fluid (CSF) 30 days after ide-cel treatment indicates sufficient CNS penetration, which is crucial for the treatment of CNS-involved MM.
Spinal MRI Findings
Maulhardt presented the spinal MRIs of a patient which showed a complete CNS response 30 days after ide-cel treatment. This visual evidence further supports the efficacy of the therapy in treating CNS myeloma. 2: The detailed analysis of these spinal MRIs provides valuable insights into the mechanism of action of ide-cel in the CNS and helps to better understand the treatment process.
