In a long-term follow-up of a Chinese phase II study reported in the Journal of Clinical Oncology, Wang et al found that the combination of anti–B-cell maturation antigen (BCMA) and anti-CD19 chimeric antigen receptor (CAR) T cells produced durable responses and favorable survival outcomes in patients with relapsed or refractory multiple myeloma.
In the multicenter study, 62 patients enrolled between May 2017 and May 2020 received an infusion of a combination of anti-BCMA CAR T cells and anti-CD19 CAR T cells at a dose of 1 × 106 cells/kg on day 0, after conditioning with cyclophosphamide at 750 mg/m2 on day –5 and fludarabine at 30 mg/m2 on days –5, –4, and –3. Patients had received a median of four prior lines of therapy (range = 2–17).
Responses and Survival
Median follow-up was 21.3 months. Partial response or better was achieved in 57 (92%) of 62 patients, with complete response or better in 37 (60%). Among 56 patients evaluable for measurable residual disease (MRD), MRD negativity (10–5) was found in 43 (77%).
Estimated median duration of response was 20.3 months (95% confidence interval [CI] = 9.1–31.5 months). Median duration of response was not reached in patients with complete response or better; 23 (62%) had ongoing responses at last follow-up, with durations ranging from 10.5 to 45.8 months.
Median progression-free survival was 18.3 months (95% CI = 9.9–26.7 months); 12- and 24-month rates were 89% and 67% among patients with complete response or better at 3 months after CAR T-cell infusion in landmark analysis. Median progression-free survival was not reached among patients with complete response or better. Median overall survival among all patients was not reached, with 12- and 24-month rates of 92% and 84% among patients with complete response or better at 3 months after CAR T-cell infusion.
Factors such as disease stage, high-risk cytogenetic profile, tumor burden, and BCMA expression were not significantly associated with progression-free or overall survival. Compared with patients without extramedullary disease, the 15 patients with extramedullary disease had poorer progression-free survival (median = 8.3 vs 21.4 months) and overall survival (median = 12.3 months vs not reached); on multivariate analysis, extramedullary disease was associated with significantly poorer overall survival (hazard ratio = 2.28, 95% CI = 1.11–13.91).
Toxicity
The most common adverse events after CAR T-cell infusion were cytokine-release syndrome (CRS) and hematologic toxicity. CRS occurred in 95% of patients and was grade ≥ 3 in 10%. Neurologic toxicity occurred in 11% of patients and was grade ≥ 3 in 3%. Late adverse effects (> 3 months after infusion) were rare, except for B-cell aplasia (any grade in 30%), hypogammaglobulinemia (any grade in 42%), and infections (grade ≥ 3 in 30%). One patient died from CRS. Three patients died within 2 months of infusion, due to intracranial hemorrhage in two and craniofacial infection in one, with none of these deaths considered related to treatment.
The investigators concluded, “The combination of anti-BCMA and anti-CD19 CAR T cells induced durable response in patients with relapsed or refractory multiple myeloma, with a median progression-free survival of 18.3 months and a manageable long-term safety profile.”
Kailin Xu, MD, of the Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported in part by grants from the Program of National Natural Science Foundation of China. For full disclosures of the study authors, visit ascopubs.org.
