The chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel (cilta-cel) has a favorable risk-benefit profile in Chinese patients with relapsed/refractory multiple myeloma (RRMM), according to research published in the Journal of Clinical Oncology.
A single infusion of cilta-cel yielded “early, deep, and durable responses,” with an overall response rate (ORR) of nearly 90%, researchers reported.
“There is a high unmet need for effective treatment options in patients with RRMM in China, where approved therapies have demonstrated ORRs of just 29%-36%,” the researchers noted.
The team conducted the phase 2 CARTIFAN-1 study (ClinicalTrials.gov Identifier: NCT03758417) to test cilta-cel in patients with RRMM from 8 sites in China. All patients had received 3 or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug.
There were 48 patients who received a single infusion of the CAR T-cell therapy after lymphodepletion. The median age at enrollment was 61 years (range, 30-72), the median time since diagnosis was 3.7 years, and the median number of prior lines of therapy was 4 (range, 3-9).
The primary endpoint was ORR. At a median follow-up of 18 months, the ORR was 89.6%, and 77.1% of patients had a complete response or better. The median time to first response was 0.95 months, and the mediation duration of response was not reached.
The researchers pointed out that the ORR in CARTIFAN-1 was comparable to the 97.9% ORR seen in the CARTITUDE-1 trial (ClinicalTrials.gov Identifier: NCT03548207), which tested cilta-cel in US patients.
The 18-month progression-free survival rate in CARTIFAN-1 was 66.8%, and the 18-month overall survival rate was 78.7%. The median progression-free survival and overall survival were not reached.
Most patients (85.4%) experienced infections, with 37.5% having grade 3-4 infections. Most patients (97.9%) developed cytokine release syndrome (CRS) as well, and 35.4% had grade 3-4 CRS. The median time to CRS onset was 7 days, and the median duration was 5 days.
“The incidence of grade 3-4 CRS events (35%) was higher than that in CARTITUDE-1 (4%), potentially because of increased use of face mask oxygen supplementation in China as part of supportive care,” the researchers noted.
In CARTIFAN-1, there were 2 events of grade 1 immune effector cell-associated neurotoxicity syndrome in 1 patient. Another patient experienced grade 1 memory impairment and grade 2 leukoencephalopathy.
Ten deaths occurred after cilta-cel infusion, and 8 of these were due to treatment-related adverse events. The 8 deaths were due to hemorrhage in the context of grade 4 thrombocytopenia with no platelet transfusion available, sudden cardiac death with hemoglobin below 50 g/L without transfusion available, septic shock, hepatic failure, pneumonia, intracranial hemorrhage in the context of grade 4 thrombocytopenia with limited platelet transfusion, multiple organ failure, and pulmonary mycosis.
“There is a high unmet need for effective therapies for patients with relapsed/refractory multiple myeloma in China,” wrote Charles Craddock, MD, associate editor of the Journal of Clinical Oncology.
“The results of this study confirm evidence of activity of cilta-cel and its potential role as a new treatment option in this patient population. Supportive care strategies with the potential to reduce infection-related morbidity and mortality are required.”
Disclosures: This research was supported by Janssen Research & Development, LLC, and Legend Biotech USA Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Mi J-Q, Zhao W, Jing H, et al. Phase II, open-label study of ciltacabtagene autoleucel, an anti–B-cell maturation antigen chimeric antigen receptor–T-cell therapy, in Chinese patients with relapsed/refractory multiple myeloma (CARTIFAN-1). J Clin Oncol. Published online October 21, 2022. doi:10.1200/JCO.22.00690