Anito-cel Yields Enduring Efficacy in Relapsed/Refractory Multiple Myeloma

Anitocabtagene autoleucel (anito-cel; previously CART-ddBCMA) produced deep, enduring efficacy among patients with relapsed/refractory multiple myeloma, according to findings from the phase 2 iMMagine-1 trial (NCT05396885) presented in a poster session at the 22nd Annual International Myeloma Society Meeting and Exposition.¹

With a median follow-up of 12.6 months, the study therapy yielded an objective response rate (ORR) of 97%, which included a stringent complete response (CR) or CR rate of 68%. Additionally, 93% (n = 70/75) of evaluable patients achieved minimal residual disease (MRD) negativity at a 10^–5 sensitivity. Data also showed a median time to first response of 1.0 month (range, 0.9-13.4) and a median time to MRD negativity of 1.0 month (range, 0.9-6.4).

Anito-cel elicited a progression-free survival (PFS) rate of 91.9% (95% CI, 85.0%-95.7%) at 6 months and 79.3% (95% CI, 68.6%-86.7%) at 12 months. Additionally, the 6-month and 12-month overall survival (OS) rates were 96.6% (95% CI, 91.1%-98.7%) and 95.2% (95% CI, 88.7%-98.0%), respectively.

“Anito-cel utilizes a novel, synthetic, compact and stable D-Domain binder that facilitates high transduction efficiency, CAR positivity, and CAR density on the T-cell surface and has a fast off-rate,” lead study author Gurbakhash Kaur, MD, an assistant professor of Medicine, Hematology, and Medical Oncology at Mount Sinai Health System, wrote with co-authors in the poster.¹ “Anito-cel demonstrated deep and durable efficacy at a median follow-up of 12.6 months….The anito-cel safety profile [was] predictable and manageable.”

In the registrational phase 2 iMMagine-1 study, patients first underwent leukapheresis prior to anito-cel manufacturing; investigators administered bridging therapy as needed. Lymphodepleting chemotherapy consisting of cyclophosphamide at 300 mg/m² and fludarabine at 30 mg/m² occurred at 5, 4, and 3 days prior to anito-cel infusion, and investigators followed up with patients for response and safety assessments for up to 24 months. Patients received anito-cel at a target dose of 115 x 10⁶ CAR-positive T cells.

The trial’s primary end point was ORR based on independent review committee (IRC) assessment per International Myeloma Working Group guidelines. Secondary end points included the sCR or CR rate, duration of response, time to initial response, PFS, and OS.²

Patients 18 years and older with relapsed/refractory multiple myeloma and at least 3 prior regimens of systemic therapy including a proteasome inhibitor, immunomodulatory drugs, and anti-CD38 antibodies were eligible for enrollment on the study. Other eligibility criteria included having documented measurable disease, an ECOG performance status of 0 or 1, and a life expectancy of more than 12 weeks.

Of 129 patients who underwent leukapheresis, 118 continued to lymphodepletion, and 117 received a dose of anito-cel. Overall, investigators noted successful anito-cel manufacturing in 99% of patients.

Among 117 patients who received anito-cel, the median age was 64 years (range, 38-78), and most were male (56%) and White (76%). Most of the study population had an ECOG performance status of 1 (54%), triple-refractory disease (86%), prior autologous stem cell transplant (79%), and bridging therapy (75%). The median number of prior lines of treatment was 3 (range, 3-8), and 51% received 3 prior lines of treatment.

Overall, 85% of patients experienced cytokine release syndrome (CRS) at grade 1 or less. The median time to onset was 4 days (range, 1-17), and the median duration was 2 days (range, 1-9). The most common supportive measures for those who experienced CRS included tocilizumab (Actemra; 77%), and dexamethasone (73%).

Most patients had no immune effector cell-associated neurotoxicity syndrome (ICANS; 92%), and all events resolved during the study. The median time to ICANS onset was 7 days (range, 2-10), and the median duration was 4 days (range, 1-12). The most common prophylactic measures for this group included dexamethasone (5%), tocilizumab (3%), anakinra (Kineret; 1%), and siltuximab (Sylvant; 1%).

Apart from CRS and ICANS, the most common treatment-emergent adverse effects (TEAEs) of any grade included neutropenia (68%), fatigue (36%), hypogammaglobulinemia (34%), and headaches (30%). Grade 3/4 TEAEs were mostly hematologic toxicities, such as neutropenia (66%), anemia (24%), and thrombocytopenia (24%).

According to the investigators, anito-cel is also under evaluation as part of the phase 3 iMMagine-3 trial (NCT06413498). The trial is currently enrolling patients and will assess anito-cel vs standard-of-care therapy in relapsed/refractory multiple myeloma following 1 to 3 prior lines of treatment.

References

1. Kaur G, Freeman CL, Dhakal B, et al. Phase 2 registrational study of anitocabtagene autoleucel for relapsed and/or refractory multiple myeloma (RRMM): updated results from iMMagine-1. Presented at the 22nd Annual International Myeloma Society Meeting and Exposition; September 17-20, 2025; Toronto, Canada. Abstract PA-288.
2. Study of anitocabtagene-autoleucel in relapsed or refractory multiple myeloma (iMMagine-1) (iMMagine-1). ClinicalTrials.gov. Updated July 16, 2025. Accessed September 23, 2025. https://tinyurl.com/29pr2vyr