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Novel CAR T-Cell Therapy for Resistant Myeloma in Early-Phase Study

By: Lauren Harrison, MD, MS
Posted: Thursday, July 21, 2022

A novel version of a chimeric antigen receptor (CAR) T-cell therapy has demonstrated clinical activity among patients with relapsed or refractory multiple myeloma. This CAR T-cell therapy uses a synthetic binding domain—named a D-domain (dd)—that targets B-cell maturation antigen (BCMA). Matthew J. Frigault, MD, of Massachusetts General Hospital, Boston, presented the early results of a phase I trial testing this investigational immunotherapy (CART-ddBCMA) at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 8003).

This study enrolled 25 patients with multiple myeloma who had undergone a median of five prior lines of therapy. Patients received 30 mg/m2 of fludarabine and 300 mg/m2 of cyclophosphamide for 3 days as lymphodepletion. CART-ddBCMA was administered at a dose of either 100 x 106 CAR-positive T cells or 300 x 106 CAR-positive T cells. Patients were monitored for adverse effects as well as response to therapy.

After a median follow-up of 9.8 months, all 25 patients were evaluable for safety, and 24 were evaluable for efficacy. The overall response rate was 100%, since 67% of patients achieved a complete response and 88% achieved a very good partial response or better. Conversion to a complete response did occur with longer follow-up, and some patients achieved it as late as 9 months after CAR T-cell infusion. A total of 20 patients were evaluable for measurable residual disease, and 85% have achieved a response of at least 10-5. Among the first six patients who were treated, four continue to be in a complete response 18 months after infusion. The progression-free survival and overall survival were not yet evaluable, because 79% of patients were in ongoing response at the time of data cutoff.

All enrolled patients experienced cytokine-release syndrome, but only one patient in the higher-dosage group had grade 3 cytokine-release syndrome. Four patients developed immune effector cell–associated neurotoxicity syndrome. Standard management led to resolution of these toxicities within 30 days.

Disclosure: For a full list of authors’ disclosures, visit coi.asco.org.


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