Multidose CAR-T shows durable efficacy for advanced multiple myeloma
Click Here to Manage Email Alerts
An investigational chimeric antigen receptor T-cell therapy provided via multiple infusions induced a 100% overall response rate among adults with relapsed or refractory multiple myeloma, results from a pilot study showed.
More than half of patients who received the regimen remained disease-free 18 months after their initial round of therapy, according to data presented during European Hematology Association Hybrid 2022 Congress.
Background
ARI0002h is an autologous, gene edited CAR T-cell therapy that targets the B-cell maturation antigen (BCMA) on the surface of cancer cells.
“Since its FDA approval in 2017, CAR T-cell therapy has [become] a staple of treatment for blood cancers, such as multiple myeloma,” Carlos Fernández de Larrea, MD, PhD, associate professor of medicine at University of Barcelona, said during a press conference.
“ARI0002h — an academic, humanized CAR-T against BCMA — is a promising therapy for patients with relapsed or refractory multiple myeloma,” he added. “ARI0002h production is fast and feasible, and patients achieved deep and sustained responses, with low-grade toxicity.”
Methodology
CARTBCMA-HCB-01 is a Spain-based multicenter trial evaluating the safety and efficacy of ARI0002h for adults with relapsed or refractory multiple myeloma who received at least two previous lines of therapy — including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody — and were refractory to the last line of treatment.
Researchers enrolled 35 patients (median age, 61 years), 30 of whom received ARI0002h and could be included in the analysis.
Study protocol permitted bridging therapy between apheresis and the first infusion of CAR T cells.
Patients received lymphodepleting chemotherapy followed by fractionated infusions (10%/30%/60%) of ARI002h at a targeted dose of 3 × 106/kg CAR T cells.
Investigators provided a second dose of ARI0002 to patients who had any response to the first fractionated dose without serious complications. Overall response rate, as well as rates of cytokine release syndrome and neurologic toxicity, served as the study’s primary endpoints.
Median follow-up among patients alive as of the data cutoff point was 16 months.
Key findings
All 30 patients treated with ARI0002 achieved an initial response to therapy, including 93% with a very good partial response or stringent complete response. Sixty-three percent of patients achieved complete remission as of a 28-day follow-up evaluation.
Researchers reported a 96% minimal residual disease-negative rate at day 28 following the final fractionated infusion, with 92% remaining MRD-negative at day 100 after infusion.
Results showed 80% of patients remained alive at 16 months. Nearly three-quarters (73%) remained alive at 18 months, with more than half (53%) of those patients remaining progression free.
Twenty-four patients (86%) received a second infusion of ARI0002 at a dose level of 1.2 to 3 × 106 CAR T cells/kg. Seven of these patients (29%) demonstrated an improved response to therapy after the second infusion.
The investigators noted “mild” CRS among 90% of patients, with no cases of treatment-related neurotoxicity.
Common treatment-related hematologic adverse events included neutropenia (97%), anemia (85%) and thrombocytopenia (79%).
Clinical implications
“ARI0002h is an efficacious treatment for relapsed or refractory multiple myeloma, with deep and durable responses and a favorable safety profile,” de Larrea said. “Importantly, the response may be boosted using a second dose.”
Collapse
de Larrea CF, et al. Abstract S103. Presented at: European Hematology Association Hybrid 2022 Congress; June 9-12, 2022.
Read more about
Click Here to Manage Email Alerts