First-in-Class Targeted Cellular Therapy Under Study in Resistant Multiple Myeloma
Posted: Monday, January 3, 2022
Sham Mailankody, MBBS, of Memorial Sloan Kettering Cancer Center, New York, and colleagues evaluated the safety and efficacy of MCARH109—the first-in-class G protein coupled receptor class C group 5 member D (GPRC5D) targeted chimeric antigen receptor (CAR) T-cell therapy—in patients with resistant multiple myeloma. Their results, presented during the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 827), suggested a manageable safety profile for MCARH109, with no unexpected or serious toxicities reported.
“Efficacy is promising in heavily pretreated relapsed/refractory multiple myeloma, reflected in high rates of clinical response as well as [measurable residual disease] negativity, including at doses as low as 25 x 106 CAR T cells,” the study authors noted. “Clinically important, all six patients who relapsed after B-cell maturation antigen CAR T-cell therapy responded to GPRC5D targeted CAR T-cell therapy, including two patients who achieved a stringent complete response.”
This phase I trial enrolled 18 patients with relapsed or refractory multiple myeloma. Participants were administered lymphodepleting chemotherapy with fludarabine and cyclophosphamide for 3 days, followed by a single infusion of MCARH109. Cohorts included 25 x 106, 50 x 106, 150 x 106, and 450 x 106 viable CAR-positive T cells.
Of the total population, 12 patients completed the MCARH109 infusion, and the median number of prior therapies was 8. Almost all (n = 11) participants were refractory to the last line of therapy, and all patients were refractory to bridging therapy. Although no dose-limiting or neurologic toxicities were reported, cytokine-release syndrome affected 11 patients, and 3 individuals had grade 1 nail changes that were possibly treatment-related.
The majority (n = 10) of patients had at least a minimal response or better at the 2-week mark, including two minimal, three partial, three very good, and two stringent complete responses. Notably, there was robust MCARH109 expansion in the peripheral blood across the first three dose levels, according to quantitative polymerase chain reaction. At the median follow-up of 13 weeks, nine patients were progression-free.
Disclosure: For full disclosures of the study authors, visit ash.confex.com.
