Anito-Cel Drives Durable Responses in R/R Multiple Myeloma

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Treatment with the BCMA-directed, autologous CAR T-cell therapy anitocabtagene autoleucel (anito-cel; CART-ddBCMA) generated durable responses in patients with relapsed/refractory multiple myeloma who received at least 3 prior lines of therapy, according to data from the phase 2 iMMagine-1 trial (NCT05396885).

Findings presented at the 2025 European Hematology Association Congress demonstrated that at a median follow-up of 12.6 months (range, 5-29), patients treated with anito-cel (n = 117) achieved an overall response rate (ORR) of 97%, which comprised a stringent complete response (sCR)/CR rate of 68%, a very good partial response (PR) rate of 18%, and a PR rate of 12%.

Notably, a minimal residual disease (MRD)–negativity rate of 93% at a 10–5 sensitivity was reported in evaluable patients (n = 75). The median time to response (n = 114) was 1.0 month (range, 0.9-13.4), and the median time to MRD negativity (n = 70) was 1.0 month (range, 0.9-6.4).

“Anito-cel utilizes a novel, synthetic antigen-binding domain called the D-Domain, which allows for high transduction efficiency, CAR positivity, and CAR density on the T-cell surface. Coupled with a fast off rate and ability to detach from the BCMA target, [this provides] us with a safe and efficacious product,” lead study author Gurbakhash Kaur, MD, said during the presentation.

Kaur is an assistant professor of medicine, hematology and medical oncology at Mount Sinai in New York, New York.

A Dive Into Anito-Cel and iMMagine-1

The BMCA-directed CAR T-cell therapy features a novel D-Domain binder, which allows for a lower total cell dose due to its size. D-Domain CARs are also stable and lack tonic signaling.

Prior data from a phase 1 study (NCT04155749) showed that at a median follow-up of 38.1 months, anito-cel led to a median progression-free survival (PFS) of 30.2 months and a median overall survival (OS) that was not reached (NR) in patients with relapsed/refractory multiple myeloma after at least 3 prior lines of therapy (n = 38).

The phase 2 iMMagine-1 trial enrolled patients with relapsed/refractory multiple myeloma who received at least 3 prior lines of therapy that included an anti-CD38 antibody, an immunomodulatory drug (IMiD), and a proteasome inhibitor. Patients needed to be refractory to their last line of therapy, have evidence of measurable disease, and have an ECOG performance status of 0 or 1.

After screening, enrolled patients underwent leukapheresis; bridging therapy was permitted during the manufacturing of anito-cel. Patients then received lymphodepleting chemotherapy consisting of 30 mg/m2 of fludarabine and 300 mg/m2 of cyclophosphamide on days –5, –4, and –3. Anito-cel was administered on day 0 at a target dose of 115 x 106 CAR-positive T cells.

ORR per 2016 International Myeloma Working Group criteria served as the trial’s primary end point. Secondary end points included sCR/CR rate and ORR in patients limited to 3 prior lines of therapy.

As of the data cutoff date of May 1, 2025, 129 patients were enrolled and underwent leukapheresis; 118 proceeded to lymphodepletion. Reasons for discontinuation prior to lymphodepletion were withdrawal of consent (n = 4), disease progression (n = 4), intercurrent illness (n = 1), investigator decision (n = 1), and loss of eligibility due to myocardial infarction (n = 1). One additional patient withdrew consent after lymphodepletion and prior to the administration of anito-cel, leaving 117 patients in the evaluable population.

In the evaluable population, the median age was 64 years (range, 38-78), and half of patients were 65 years of age or older. The majority of patients were male (56%), White (76%), and had an ECOG performance status of 1 (54%). Fifteen percent of patients had extramedullary disease, and 38% had high-risk cytogenetics. The median time since diagnosis was 7.2 years (range, 1.0-23.1), and 79% of patients underwent a prior autologous stem cell transplant.

All patients were refractory to their last line of therapy, 86% were triple-class refractory, and 40% were penta-drug refractory. The median prior lines of therapy was 3 (range, 3-8), and 51% received only 3 prior lines of therapy.

Seventy-five percent of patients received bridging therapy prior to anito-cel, and 9% of patients received anito-cel in the outpatient setting.

Additional Efficacy and Safety Data

Further efficacy data showed that the 6- and 12-month PFS rates were 91.9% (95% CI, 85.0%-95.7%) and 79.3% (95% CI, 68.6%-86.7%), respectively. The respective 6- and 12-month OS rates were 96.6% (95% CI, 91.1%-98.7%) and 95.2% (95% CI, 88.7%-98.0%).

Regarding safety, cytokine release syndrome (CRS) occurred at grade 1 in 70% of patients and grade 2 in 15% of patients. One patient (1%) experienced grade 5 CRS. The median time to onset of CRS was 4 days (range, 1-17), and the median duration was 2 days (range, 1-9). CRS did not occur or resolved within 7 days in 80% of patients; no CRS or resolution within 10 days was reported in 97% of patients.

Regarding CRS management, 71% of patients received either a single 10-mg dose of dexamethasone or no dexamethasone. Overall supportive measures included tocilizumab (Actemra; 77%), dexamethasone (73%), anakinra (Kineret; 11%), siltuximab (Sylvant; 3%), vasopressor (1%), and intubation/mechanical ventilation (1%).

Any-grade immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 8% of patients at grade 1 (3%), grade 2 (3%), or grade 3 (1%). No delayed or non-ICANS neurotoxicities were reported. The median time to onset of ICANS was 7 days (range, 2-10), and the median duration was 4 days (range, 1-12). ICANS management included tocilizumab (3%), dexamethasone (5%), anakinra (1%), and siltuximab (1%).

The most common treatment-emergent adverse effects (TEAEs) included neutropenia (any-grade, 68%; grade 3/4, 66%), anemia (27%; 24%), thrombocytopenia (24%; 24%), fatigue (36%; 3%), hypogammaglobulinemia (34%; 1%), headache (30%; 2%), hypophosphatemia (29%; 2%), nausea (27%; 1%), diarrhea (27%; 1%), hypertension (20%; 10%), and hypokalemia (20%; 2%).

Any-grade infections were reported in 52% of patients, and 9% had grade 3/4 infections. The most common infections were upper respiratory tract infection (any-grade, 13%; grade 3/4, 2%), urinary tract infection (7%; 2%), and COVID-19 (6%; 1%).

iMMagining the Next Steps

Anito-cel is being evaluated against standard-of-care therapy in the phase 3 iMMagine-3 trial (NCT06413498). The ongoing study is enrolling patients with relapsed/refractory multiple myeloma who received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and an IMiD.

Reference

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: 2025 EHA Congress; June 12-15, 2025; Milan, Italy. Abstract S201.