Bristol Myers Squibb and 2seventy bio's CAR-T Ide-Cel Effects Responses in CNS-Involved R/R Multiple Myeloma

This article originally appeared on our sister site, OncLive®.

Bristol Myers Squibb and 2seventy bio's idecabtagene vicleucel (ide-cel, marketed as Abecma), an FDA-approved chimeric antigen receptor T-cell (CAR-T) therapy, brought about responses in patients with relapsed/refractory (r/r) multiple myeloma (MM) affecting the central nervous system (CNS), in data from a real-world analysis presented in a poster at the 66th American Society of Hematology (ASH) Annual Meeting, held December 7-10, 2024, in San Diego, California.

Among 10 patients with CNS-involved MM who had a median of 4.7 months of follow-up, 7 patients (70%) had no CNS relapse after treatment with ide-cel, with an estimated median progression-free survival (PFS) of 10.5 months and estimated median overall survival (OS) of 12.9 months.

“We report for the first time that BCMA-directed CAR T-cell therapy is an effective and feasible treatment approach in [patients with] MM–CNS,” Markus Maulhardt, MD, of University Hospital Goettingen in Germany, and colleagues wrote.

Poor outcomes are associated with MM with significant CNS manifestation, which constitutes a rare form of the disease. Notably, the FDA's approvals of ide-cel and other CAR-T therapies were based on clinical trials that excluded patients with CNS disease; as such, existing data on the efficacy of CAR-T in patients with CNS-involvement is limited.

Maulhardt and colleagues carried out a multicenter retrospective study, which included 153 patients treated with ide-cel at 7 tertiary care centers in Germany and Switzerland between March 2022 and May 2024. Analysis of the this population determined the frequency of CNS disease and grouped patients accordingly. CNS symptoms and CNS myeloma were reported in 17 patients (11%); although, in only 10 patients (6.5%) was CNS disease confirmed according to a definition that covered intradural and/or intraparenchymal lesions or detection of myeloma cells in the cerebrospinal fluid (CSF). Uncertain CNS manifestation was recorded in 7 other patients with neurological symptoms that were likely due to extradural, extramedullary disease, or myelon compression.

Among the 10 patients with confirmed CNS myeloma, there were 6 women and 4 men. The median age at the time of treatment with ide-cel was 61 years. Eastern Cooperative Oncology Group (ECOG) performance statuses greater than 2 at the time of treatment were noted in 4 patients (40%). Five patients (50%) had high-risk cytogenetics including 1q gain. Furthermore, 9 patients (90%) had triple-class refractory disease and 7 patients (70%) had disease that was penta-class refractory; 9 of the patients (90%) had previously been treated with high-dose chemotherapy and autologous stem cell transplant; and 2 patients (20%) had previously been treated with allogeneic stem cell transplant. The time between diagnosis and treatment with ide-cel ranged from 3.5 to 13.6 years (median, 5.6).

All 10 had secondary CNS myeloma at relapse/progression rather than CNS disease at diagnosis. They had received between 1 and 7 therapies (median, 3) before CNS myeloma developed. Five (50%) had parenchymal lesions, 6 (60%) had leptomeningeal sites, and 2 (20%) had central nerve lesions. All had neurological symptoms. They had received CNS therapies including CNS penetrating systemic myeloma therapy (70%), additional radiotherapy (30%), intrathecal therapy (30%), and surgery plus radiation (20%).

In the 10 patients, the best serologic response on bridging before ide-cel was complete response (CR) in 50%, partial response (PR) or very good partial response (VGPR) in 40%, and progressive disease (PD) in 10%. The serologic response at ide-cel infusion was CR in 40%, PR or VGPR in 40%, stable disease in 10%, and unknown in 10%. The best serologic response after ide-cel was CR in 50% and PR in 50%.

As of the last follow-up, 40% had relapse of MM after ide-cel; at last follow-up, 40% were in serologic CR, 20% in PR, and 40% had PD. Six patients remained alive.

Maulhardt presented the spinal MRIs of a patient which showed there was a complete CNS response 30 days after ide-cel treatment. “We were able to collect CSF from the same patients and we were able to show CAR T-cells in the CSF 30 days after ide-cel treatment showing sufficient CNS penetration by CAR T-cells,” he said.

Some patients experienced immune effector–cell associated neurotoxicity syndrome, but none had cases of grade 2 or higher. Cytokine release syndrome (CRS) of grade 2 or 3 was reported in 6 patients, but none had grade 4 CRS.

The poster also reported on a matched-pair analysis performed on all 17 patients with unconfirmed CNS myeloma, who were compared with patients in the ide-cel treated population without CNS manifestations. They were matched based on Revised International Staging System stage, number of prior lines of therapy, triple and penta-class refractory status, and remission status. The median PFS and OS were 10.5 months and 13 months for the CNS disease cohort versus 8.5 months and 10.6 months, respectively, in the non-CNS myeloma cohort. The rate of CR, VGPR, or PR was 82% in the CNS myeloma cohort vs 80% in the non-CNS myeloma cohort.

“Our data—albeit obtained from a small cohort—showed a high remission rate for CNS manifestations after ide-cel treatment. Therefore, CAR T-cell therapy can be considered for eligible [patients with] r/r MM with a history of CNS involvement,” Maulhardt concluded.

REFERENCE
1. Maulhardt M, Berning P, Hanoun C, et al. Efficacy of idecabtagene vicleucel (ide-cel) in patients with relapsed/refractory multiple myeloma and prior central nervous system manifestation: a retrospective real-world analysis. Blood. 2024;144(suppl 1):4759. doi:10.1182/blood-2024-202467