CAR-T for NMOSD Demonstrates Manageable Safety in Phase 1 Trial

It was previously announced that CT103A received FDA clearance of its investigational new drug application for the treatment of relapsed/refractory (r/r) multiple myeloma.

This content originally appeared on our sister site, NeurologyLive.

CT103A (NCT04561557), a chimeric antigen receptor (CAR) T-cell therapy directed at B-cell maturation antigen (BCMA) and intended to treat relapsed or refractory (r/r) AQP4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD), showed a manageable safety profile in recently published data from an ongoing open-label, single-arm, phase 1 clinical trial (NCT04561557).

All 12 treated patients experienced adverse events of grade 3 or higher, the most common of which were hematological toxic effects, including leukopenia (100%), neutropenia (100%), anemia (50%), and thrombocytopenia (25%), and most of which resolved within 4 weeks. Serious adverse effects included cytomegalovirus infection (25%), coagulation disorder (8%), and pneumonia (8%).

"Our data show that CAR-BCMA T-cell therapy might induce clinical remission of NMOSD associated with the rapid removal of AQP4 autoantibodies, and longer-term observation will be warranted," lead author Chuan Qin, MD, associate professor, department of neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, and colleagues wrote.1

The patients were treated from September 22, 2020, to December 24, 2021. Most of the patients treated were women (83.3%), and the median age of the participants was 49.5 years (range, 30–67). Seven (58%) of the patients developed an infection during the course of the study; however, none of these infections were grade 4. Eleven patients had not relapsed at a median follow-up of 5.5 months, and generally all of the patients reported improvements in terms of disabilities and quality of life outcomes. Additional observations included a downward trend in AQP4 serum antibodies in 11 patients and an association observed in 17% of patients between CAR T-cell expansion and responses that continued through 6 months post-infusion.

Qin and colleagues wrote that during the follow-up period, “we observed reduced attack frequency, and stabilized or improved neurological disability measures in most patients, indicating a preliminary clinical efficacy of CAR-BCMA therapy in NMOSD. The possibility that the lymphodepletion conditioning regimen before CT103A infusion was responsible for an apparent decrease in relapses should also be considered.”

Study limitations included that newly approved therapies were not available for the treatment of NMOSD at the time of the trial in China such as eculizumab, satralizumab, and inebilizumab. Hence, the patients in the trial were not treated with those approved therapies and may be explored more in future research with a parallel treatment arm, noted the authors. Furthermore, the trial had a brief follow-up duration which may have significantly limited the clinical outcomes interpretation as a longer period would have produced more accurate safety comparisons. The design of the trial and the small sample of patients may have restricted the conclusions drawn from the results. In addition, authors noted that CAR T-cells that target AQP4-IgG would have been more accurate for disease control and should be considered in future investigations.

“In this NMOSD cohort, sustained inhibition of humoral immunity, as well as low levels of AQP4-IgG in the serum, were observed. Most patients showed no infection without regular replacement therapy, suggesting that sustained humoral immunity suppression was well tolerated in NMOSD patients,” Qin et al noted.1

It was previously announced that CT103A received FDA clearance of its investigational new drug application for the treatment of r/r multiple myeloma.2 Currently, CT103A is being evaluated for the treatment of r/r MM in the phase 1/2 FUMANBA-1 (NCT05066646) clinical trial in China. The trial reported an objective response rate of 94.9% with a median follow-up of 9 months (range, 1.2 to 19.6) in 79 patients across 14 clinical centers that were given the recommended phase 2 dose of 1.0×106 CAR-T cells/kg. As for safety, all cases of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were grade 1 to grade 2 and resolved with supportive treatment.

1. Qin C, Tian DS, Zhou LQ, et al. Anti-BCMA CAR T-cell therapy CT103A in relapsed or refractory AQP4-IgG seropositive neuromyelitis optica spectrum disorders: phase 1 trial interim results. Signal Transduct Target Ther. 2023;8(1):5. Published 2023 Jan 4. doi:10.1038/s41392-022-01278-3
2. IASO Bio announces US FDA approval of clinical trial application for BCMA CAR-T CT103A for relapsed/refractory multiple myeloma. News release. IASO Biotherapeutics. December 22, 2022.
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