CT103A Displays Manageable Safety Profile in Relapsed, Refractory AQP4-IgG Seropositive NMOSD


Results from on ongoing phase 1 trial showed a favorable safety profile with CT103A in patients with NMOSD.

Recently published interim results from an ongoing open-label, single-arm, phase 1 trial of CT103A (NCT04561557), a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA), highlighted the therapy’s manageable safety profile. The study provided evidence that CT103A could potentially work as a safe therapy for patients with relapsed or refractory AQP4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD).

In terms of safety, all the treated patients (n = 12) had adverse events of grade 3 or higher, the most common being hematological toxic effects, including leukopenia (100%), neutropenia (100%), anemia (50%), and thrombocytopenia (25%), most of which were resolved within 4 weeks. Notably, the serious adverse effects observed in treated patients were cytomegalovirus infection (25%), coagulation disorder (8%), and pneumonia (8%).

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, “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.”1

From September 22, 2020, to December 24, 2021, patients were administered with a CAR-BCMA infusion, most of which were women (83.3%). Participants had a median age of 49.5 years old (range, 30–67). Over the course of the study, 7 (58%) of the patients developed an infection; however, no grade 4 infections occurred. Over a median follow-up of 5.5 months,11 patients had no relapse and generally all of the patients reported improvements with disabilities and quality of life outcomes. Additionally, a downward trend in AQP4 serum antibodies was observed in 11 patients’, as well as an association between CAR T-cell expansion and responses that continued over the 6 months post-infusion in 17% of the patients.

>>READ MORE: Rare, Fatal Case of Neuromyelitis Optica Post–COVID-19 Vaccination Explained

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 targets the 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

In prior coverage from our sister publication CGTLive,CT103A received FDA clearance of its investigational new drug application for the treatment of relapsed/refractory (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 the 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.http://www.iasobio.com/info.php?id=209
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