‘Exciting’ results show anito-cel CAR-T is safe, durable for high-risk multiple myeloma
Click Here to Manage Email Alerts
Key takeaways:
- Study investigators reported limited high-grade treatment-related CRS or neurotoxicity.
- More than half of study participants had an ongoing response to therapy as of the study data cutoff date.
SAN DIEGO — All 38 patients with heavily pretreated multiple myeloma responded to an investigational chimeric antigen receptor T-cell therapy, results of a phase 1 study presented at ASH Annual Meeting and Exhibition showed.
The CAR-T product, now known as anitocabtagene autoleucel — also known as anito-cel — showed low levels of key toxicities related to the use of CAR-T, including cytokine release syndrome and neurotoxicity, according to study investigators.
“We are seeing durable responses using this therapy,” Matthew J. Frigault, MD, administrative director of the cellular therapy service at Mass General Cancer Center, instructor at Harvard Medical School and member of the Healio | Cell Therapy Next Peer Perspective Board, said. “The first patient who received this therapy as part of a clinical trial will hit the 4-year survival mark this coming February.”
Background
Anito-cel (Arcellx) is an autologous, gene-edited CAR T-cell therapy that targets the B-cell maturation antigen (BCMA).
Manufacturing delays due to product demand continue to affect the administration of commercial CAR-T among individuals with multiple myeloma, according to Frigault.
“As CAR-Ts start to move into earlier lines of therapy, it exacerbates this situation by increasing the number of patients who are eligible,” he said.
Beyond manufacturing delays, the toxicities associated with certain CAR-T constructs is emerging as a differentiating factor between products, Frigault added.
“We are finding that, in the commercial experience with the addition of high-risk patients, those types of side effects may be higher than was observed in clinical trials,” he said. “Having a CAR-T product that is highly efficacious and may not have the same level of high-risk toxicities is potentially more important than issues related to manufacturing and access.”
Methodology
Frigault and colleagues conducted a phase 1 dose-expansion study to evaluate the saftey and efficacy of anito-cel among adults with heavily pretreated multiple myeloma.
At ASH they reported updated results with a minimum of 1 year of follow-up from 40 patients (median age, 66 years; range, 44-76; 58% men) with relapsed or refractory multiple myeloma who either were triple-refractory or received at least three previous treatment regimens, including a proteasome inhibitor, an immunomodulatory agent and a CD38-directed monoclonal antibody.
The updated analysis included 38 patients — all with poor prognostic risk factors — who received the CAR-T and comprised the population eligible for evaluation of clinical response and saftey.
Study participants received lymphodepletion chemotherapy followed by a single infusion of anito-cel at one of two dose levels (100 × 106 or 300 × 106 CAR T cells).
Study investigators chose the lower dose group for the dose-expansion phase of the trial due to its 100% response rate and lack of high-grade CRS.
Saftey served as the study’s primary outcome measurements, specifically incidence of treatment-related adverse events and dose-limiting toxicities. Additional endpoints included quality and duration of clinical response assessed according to International Myeloma Working Group criteria, evaluation of minimal residual disease (MRD), PFS and OS.
Key findings
At a median follow-up of 26.5 months, 95% of patients treated with anito-cel experienced CRS, with only one patient in the higher-dose group having grade 3 symptoms. The remaining study participants had grade 2 or lower CRS.
Seven patients had reported immune effector cell-associated neurotoxicity syndrome following CAR-T infusion. Two of these patients had grade 3 symptoms.
Researchers did not observe delayed neurotoxicity events or Parkinsonian-like symptoms that have been associated with BCMA-directed therapies.
The 100% overall response rate among study participants included 76% of patients with a complete response to therapy or stringent complete response.
Eighty-nine percent of patients eligible for MRD analysis achieved MRD-negativity.
Median duration of response, PFS and OS had not yet been reached as of the study’s data cut-off date. Kaplan-Meier curves showed an estimated 6-month PFS rate of 92%, decreasing to 67% at 18 months.
Clinical implications
Frigault said the results so far are “really exciting” especially because more than half of patients continue to respond to treatment at a median follow-up exceeding 2 years.
“None of the high-risk subgroups in this study have met their median PFS,” he told Healio. “It appears as if those who would be considered high risk for CAR-T are all benefitting from CART-ddBCMA.”
A phase 2 registrational study is already underway for further evaluation of anito-cel in patients with relapsed or refractory disease, Frigault said.
Collapse
Frigault MJ, et al. Abstract 1023. Presented at: ASH Annual Meeting and Exhibition; Dec. 9-12, 2023; San Diego.
Click Here to Manage Email Alerts