|The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Hematology Advisor’s conference coverage.|
Administration of chimeric antigen receptor (CAR) T-cell (CAR-T) therapy JNJ-4528 to heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM) resulted in high response and progression-free survival (PFS) rates, according to results from a phase 1b trial presented at the ASCO20 Virtual Scientific Program. JNJ-4528 contains 2 anti–B-cell maturation antigen (BCMA) single-domain antibodies.
“CARTITUDE-1 is a phase 1b/2 study,” Jesus G. Berdeja, MD, of the Sarah Cannon Research Institute in Nashville, Tennessee, and lead author and presenter of the study, said. “The primary objective of the phase 1 is to characterize the safety and confirm the phase 2 dose as informed by the LEGEND-2 study.”
The phase 1 study treated 29 patients with RRMM with JNJ-4528 with a median dose of 0.73 x 106 CAR T cells/kg. Patients had received 3 or more prior regimens or were double-refractory to a proteosome inhibitor (PI) or immunomodulatory (IMiD) agent and had received a prior anti-CD38 antibody. All patients underwent lymphodepletion with cyclophosphamide and fludarabine, and 79% received bridging therapy.
At baseline, the median patient age was 60 years, and 52% of patients were female. Patients received a median of 5 (range, 3-18) prior lines of therapy, and 86% were triple-refractory and 28% were penta-refractory. Nearly all patients were refractory to their last line of treatment. Extramedullary disease was present in 10% of patients and 27% had high-risk cytogenetics.
All patients responded to treatment, with an ORR of 100%. The stringent complete response (sCR) rate was 86%, 10% of patients had a very good partial response, and 3% had a partial response. The median time to complete response was 3 months.
During a median follow-up of 11.5 months, the 9-month PFS was 86% (95% CI, 67%-95%) and 76% of patients remained alive and progression free.
“The majority of patients continue to show [minimal residual disease] MRD-negative response rates beyond 28 days,” Dr Berdeja said. Among patients who achieved a CR, 81% were MRD-negative at 10-5 or 10-6.
The most common grade 3 or higher adverse events (AEs) were neutropenia (100%), thrombocytopenia (69%), and leukopenia (66%). Cytokine release syndrome (CRS) occurred in 93% of patients, including 1 grade 3 case and 1 grade 5 case, but all patients received medications to manage the inflammatory condition. Neurotoxicity occurred in 10% of patients, including 1 grade 3 event.
CAR T-cell expansion peaked between day 10 to 14, and at 6 months; most patients (79%) did not have detectable CAR T-cells in their peripheral blood. This suggests that “CAR-T persistence in peripheral blood did not seem to correlate with deepening of response,” Dr Berdeja said.
Dr Berdeja added that JNJ-4528 treatment “induced early, deep, and durable responses in heavily pretreated patients.” He noted that the phase 2 portion of CARTITUDE-1 is fully enrolled and additional phase 2 and phase 3 studies have been initiated.
Berdeja JG, Madduri D, Usmani SZ, et al. Update of CARTITUDE-1: A phase Ib/II study of JNJ-4528, a B-cell maturation antigen (BCMA)-directed CAR-T-cell therapy, in relapsed/refractory multiple myeloma. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 8505.
This article originally appeared on Cancer Therapy Advisor