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ESMO 2022: BCMA-Specific CAR T-Cell Therapy Using a Synthetic Binding Domain in Multiple Myeloma

By: Julia Fiederlein
Posted: Monday, September 12, 2022

According to Matthew Frigault, MD, of the Massachusetts General Hospital, Boston, and colleagues, B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapy using the novel, synthetic binding domain D-Domain (CART-ddBCMA) demonstrated clinical activity in patients with relapsed or refractory multiple myeloma. The interim results of this phase I, multicenter, first-in-human trial were presented during the European Society for Medical Oncology (ESMO) Congress 2022 (Abstract 620O).

After undergoing lymphodepletion, a total of 25 patients were administered CART-ddBCMA. Dose escalation was performed at 100 and 300 x 106 CAR-positive T cells, and the target dose of 100 x 106 was chosen for subsequent expansion. All patients experienced cytokine-release syndrome; however, just one, who was administered 300 x 106 CAR-positive T cells, had grade 3 cytokine-release syndrome. Immune effector cell–associated neurotoxicity syndrome was reported in four patients (grade ≤ 2: n = 2; grade 3: n = 2). According to the investigators, all cases resolved without sequelae with standard management.

The objective response, stringent complete response/complete response, and very good partial response or better rates were 100%, 67%, and 88%, respectively. Conversion to a complete response or stringent complete response was observed with longer follow-up, which occurred as late as 9 months. With up to 9 months of follow-up, all four patients treated with 100 x 106 CAR-positive T cells who achieved a partial response or very good partial response and were evaluable for measurable residual disease (MRD) demonstrated negativity at a sensitivity threshold of 10-5 cells. Overall, 85% of evaluable patients achieved a best MRD response at a sensitivity threshold of at least 10-5 cells.

Of the first six patients who received 100 x 106 CAR-positive T cells, 67% maintained a stringent complete response beyond 18 months; this included three patients with extramedullary disease. At data cutoff, the median durations of response, progression-free survival, and overall survival were not evaluable (79% of patients remained in an ongoing response).

Disclosure: For full disclosures of the study authors, visit

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