ASH 2020: BCMA-Targeted Antibody-Drug Conjugate in Resistant Multiple Myeloma
Posted: Monday, December 7, 2020
The B-cell maturation antigen (BCMA)-targeted antibody-drug conjugate MEDI2228 appears to be safe and active in patients with relapsed or refractory multiple myeloma, according to Shaji K. Kumar, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues. The results of this early-phase dose-escalation and dose-expansion trial, which featured an objective response rate of about 60%, were presented during the virtual edition of the 2020 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 179).
During dose-escalation, MEDI2228 was intravenously administered to a total of 82 patients in doses ranging from 0.0125 to 0.2 mg/kg every 3 weeks. In the 0.2-mg/kg cohort, two patients experienced a grade 3 or 4 dose-limiting toxicity of thrombocytopenia. As a result, the dose was de-escalated to the maximum tolerated dose of 0.14 mg/kg. Dose-limiting toxicities were not reported for other dose levels. Photophobia, thrombocytopenia, rash, increased gamma-glutamyltransferase, dry eyes, and pleural effusion were among the most commonly reported treatment-related adverse events in the 0.14-mg/kg cohort. The safety profiles were similar at lower-dose levels, although treatment-emergent adverse events occurred at lower incidence rates compared with the 0.14 mg/kg level.
Across the dose levels studied, the objective response rates were highest with the 0.14-mg/kg and 0.2-mg/kg doses (at 61% and 40%, respectively). Very good partial responses (24.4%), partial responses (36.6%), and minimal responses (7.3%) were observed in the 0.14-mg/kg cohort. Of the 10 patients who achieved a very good partial response, 4 were immunofixation-negative. MEDI2228 exhibited linear pharmacokinetics at doses greater than 0.05 mg/kg. BCMA expression in the bone marrow did not seem to differ between responders and nonresponders. In the 0.14-mg/kg cohort, a total of 36 patients discontinued treatment due to adverse events, progressive disease, patient decision, investigator decision, or death.
Disclosure: For full disclosures of the study authors, visit ash.confex.com.
