Anitocabtagene autoleucel exhibits durable efficacy in high-risk advanced multiple myeloma
Key takeaways:
- The majority of patients responded to therapy, with nearly two-thirds achieving complete response or stringent complete response.
- An estimated 95% of trial participants remained alive at 6 months.
SAN DIEGO — Anitocabtagene autoleucel exhibited durable efficacy among heavily pretreated patients with high-risk relapsed or refractory multiple myeloma, results of the phase 2 iMMagine-1 study showed.
Anitocabtagene autoleucel (Arcellx Inc. and Kite Pharma/Gilead Sciences) — often called anito-cel — also exhibited a manageable safety profile, according to researchers who presented the findings at ASH Annual Meeting and Exposition.
“The data from the iMMagine-1 study demonstrate that this is a highly active product with impressive depth of responses achieved in patients with relapsed or refractory multiple myeloma,” Ciara Louise Freeman, MD, PhD, MSc, FRCPC, MRCP, assistant member of the department of blood and marrow transplant and cellular immunotherapy at Moffitt Cancer Center, said in an Arcellx press release. “As a physician who treats many patients both inpatient and in the outpatient setting, the emerging safety profile of anito-cel is encouraging, in particular the absence of any delayed neurotoxicities reported to date.”
Anito-cel is an autologous anti-B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy with a novel D-domain binder. The agent is being developed for treatment of relapsed or refractory multiple myeloma.
A phase 1 study that included patients who had received at least three prior lines of therapy resulted in a 100% overall response rate and a 76% complete response/stringent complete response rate. An estimated 56% of patients remained progression free at 24 months.
IMMagine-1 — an ongoing phase 2 registrational trial — includes adults with triple class-exposed relapsed or refractory multiple myeloma whose disease progressed after at least three lines of treatment. All trial participants had evidence of measurable disease and had been refractory to their most recent treatment.
After leukapheresis and optional bridging therapy, patients received lymphodepletion chemotherapy with fludarabine and cyclophosphamide. They then received a single infusion of anito-cel at a target dose of 115 x 106/kg.
ORR — including stringent complete response, complete response, very good partial response or partial response — as determined by an independent review committee served as the primary endpoint.
At ASH, Freeman reported the preliminary analysis of investigator-assessed safety and efficacy for patients who had at least 2 months of follow-up after anito-cel infusion.
The analysis included 86 patients evaluable for efficacy (median follow-up, 9.5 months; minimum follow-up, 2 months) and 98 patients evaluable for safety (minimum follow-up, 1 month).
A majority (87%) of patients in the safety population were triple refractory and 41 (42%) were penta-refractory. Patients had received a median four prior lines of therapy, and nearly half (46%) had received three prior lines of therapy.
Results showed an investigator-assessed ORR of 97%, with 62% of patients achieving complete response or stringent complete response and 81% achieving very good partial response or higher per International Myeloma Working Group criteria.
Fifty-eight patients could be evaluated for minimal residual disease (MRD) testing. The majority (93.1%) achieved MRD negativity at a minimum sensitivity threshold of at least to 10-5.
Median PFS and OS had not been reached; however, researchers reported estimated 6-month PFS of 93.3% and 6-month OS of 96.5%. They reported 12-month PFS of 78.5% and 12-month OS of 96.5%.
Eleven patients (19%) developed grade 2 cytokine release syndrome, one patient experienced a grade 5 CRS event, and 17% had no CRS.
Median time to onset of CRS was 4 days (range, 1-17).
Nine patients (9%) developed immune effector cell-associated neurotoxicity syndrome (ICANS), with one grade 3 case. All cases resolved without sequelae.
Researchers reported no delayed or non-ICANS neurotoxicities among 150 patients dosed with anito-cel by data cutoff.
Three patients died due to treatment-emergent adverse events. These included one case each of CRS, retroperitoneal hemorrhage and fungal infection.
The most common grade 3 or higher treatment-emergent adverse events included neutropenia (54%), anemia (22%) and thrombocytopenia (20%).
The randomized phase 3 iMMagine-3 study is underway to compare anito-cel with standard therapy for patients with relapsed or refractory multiple myeloma who received one to three prior lines of therapy.
“We are excited to begin enrolling patients in the iMMagine-3 study and in the near future having anito-cel as an approved treatment option,” Freeman said in the release.
References:
- Arcellx announces new positive data for its iMMagine-1 study in patients with relapsed or refractory multiple myeloma to be presented during an oral presentation at the 66th ASH Annual Meeting and Exposition (press release). Available at: https://ir.arcellx.com/news/news-details/2024/Arcellx-Announces-New-Positive-Data-for-Its-iMMagine-1-Study-in-Patients-With-Relapsed-or-Refractory-Multiple-Myeloma-to-be-Presented-During-an-Oral-Presentation-at-the-66th-ASH-Annual-Meeting-and-Exposition/default.aspx. Published Dec. 8, 2024. Accessed Dec. 22, 2024.
- Freeman CL, et al. Abstract 1031. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2024; San Diego.
Perspective
Back to Top
Mansi R. Shah, MD
The results from the phase 2 IMMagine-1 trial evaluating anitocabtagene autoleucel, a B-cell maturation antigen (BCMA)-directed CAR-T therapy with a novel D-domain binder, highlight its potential to improve outcomes for patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM) — particularly high-risk patients.
Twelve percent of patients were aged older than 75 years with a median four prior lines of therapy, and 71% of patients received bridging therapy. The reported ORR of 97% and depth of response — including 62% stringent/complete responses (CR/sCR) and 93% MRD negativity — are impressive, particularly in a population with high-risk features such as extramedullary disease. Importantly, the estimated 6-month PFS and OS add weight to the early efficacy signals.
The distinct D-domain binding mechanism seems to be a critical innovation for anito-cel. The “fast-off” kinetics and high surface CAR expression may contribute to the therapy’s optimal cell killing at a lower total cell dose without prolonged inflammation — a unique feature compared with other BCMA-directed therapies. Perhaps this small d domain design may also explain the favorable neurotoxicity profile, with ICANS observed in only 9% of patients and no cases of delayed neurotoxicity, cranial nerve palsies or Parkinsonian-like symptoms. However, the cause of delayed neurotoxicity remains elusive. These improvements are particularly meaningful in a field where neurotoxicity remains a significant concern with currently available FDA approved BCMA-targeted CAR products.
Another notable advantage is the shorter manufacturing time for anito-cel, which enables earlier infusion and better disease control during the bridging period. This logistical improvement is especially relevant in RRMM, where disease progression between leukapheresis and infusion can significantly compromise outcomes. Faster turnaround times could improve patient access and treatment feasibility in real-world settings.
Although the improved neurotoxicity profile is encouraging, the 83% incidence of CRS — despite being predominantly grade 1 — highlights that CRS remains a notable issue; however, 17% of patients did not develop CRS. Median time to onset of CRS is about 4 days and the median duration is about 3 days. Additionally, high rates of grade 3 or higher hematologic adverse events, including neutropenia, suggest that prolonged cytopenias remain a burden, and may impact recovery and resource utilization.
Although anito-cel offers several advantages — faster turnaround time, lower CAR-T dose requirement and improved neurotoxicity — the short median follow-up leaves questions regarding the durability of responses. The estimated PFS and OS rates are encouraging, but longer-term data are essential to confirm these findings. Further, comparative studies against existing CAR-T therapies will be needed to determine whether these design improvements translate into a definitive clinical advantage.
In summary, anito-cel represents a promising advancement in BCMA-directed CAR T-cell therapies, with early signals of strong efficacy, a favorable neurotoxicity profile and logistical advantages through faster production. Although these results are not yet practice-changing, they mark meaningful progress and set the stage for further exploration of this therapy’s role in the evolving treatment landscape of RRMM.
Rutgers Robert Wood Johnson Medical School
Collapse
Freeman CL, et al. Abstract 1031. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2024; San Diego.