Anito-cel (anitocabtagene autoleucel) is Arcellx's BCMA-specific CAR-modified T-cell therapy utilizing the company's novel BCMA-targeting binding domain for treating patients with relapsed or refractory multiple myeloma. CART-ddBCMA is currently being evaluated in an (iMMagine-1) Phase II pivotal trial in relapsed or refractory multiple myeloma and seeks regulatory approval in collaboration with Kite. Arcellx's proprietary binding domains are novel synthetic proteins that bind specific therapeutic targets. 

At the 2025 European Hematology Association Congress, data showed that with a median follow-up of 12.6 months, the anito-cel treatment led to a 97% overall response rate (ORR) among 117 patients. This included a stringent complete/complete response (sCR/CR) rate of 68%, a very good partial response (VGPR) rate of 18%, and a partial response (PR) rate of 12%. Additionally, 93% of evaluable patients achieved minimal residual disease (MRD) negativity at a sensitivity of 10⁻⁵. The median time to respond was 1.0 months, and the median time to MRD negativity was also 1.0 months. Further efficacy data showed that the 6 and 12-month PFS rates were 91.9% and 79.3%, respectively. The respective 6 and 12-month OS rates were 96.6% and 95.2%.

Cytokine Release Syndrome (CRS) occurred in 86% of patients (Grade 1: 70%, Grade 2: 15%, Grade 5: 1%), with a median onset of 4 days and a median duration of 2 days. CRS resolved within 7 days in 80% and within 10 days in 97%. Management included tocilizumab (77%), dexamethasone (73%), and less frequently anakinra (11%) or siltuximab (3%). Immune-effector Cell-associated Neurotoxicity Syndrome (ICANS) was observed in 8% of patients (Grades 1–3); onset was 7 days, and median duration was 4 days. Management included tocilizumab (3%), dexamethasone (5%), anakinra (1%), and siltuximab (1%).

Common TEAEs included neutropenia (68%), anemia (27%), thrombocytopenia (24%), fatigue (36%), hypogammaglobulinemia (34%), headache (30%), hypophosphatemia (29%), nausea/diarrhea (27%), hypertension (20%), and hypokalemia (20%). Infections occurred in 52%, with 9% Grade 3/4. Frequent infections included Upper Respiratory Tract Infection (URTI) (13%), Urinary Tract Infection (UTI) (7%), and COVID-19 (6%).

KOL insights

"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."– Expert Opinion

Conclusion

In multiple myeloma, CAR-T cell therapy offers a personalized, one-time treatment that delivers deep and durable responses, even in heavily pretreated patients. It provides targeted killing of myeloma cells, potential for long-term remission, and minimal off-target toxicity compared to conventional therapies. Despite risks like CRS and ICANS, its evolving safety profile and strong efficacy make it a promising option in relapsed or refractory settings. The standard treatment for multiple myeloma often involves a combination of three medications- sometimes called triplet therapy. This often includes a targeted therapy, an immunomodulator, and a corticosteroid. At present, the market holds a diverse range of therapeutic alternatives for treatment, which includes proteasome inhibitors, immunomodulating agents, histone deacetylase inhibitors, monoclonal antibodies, chemotherapy, corticosteroids, nuclear export inhibitors, CAR-T cell therapy, and bispecific antibody in different lines of treatment.

Anito-cel, featuring a synthetic D-Domain binder, delivers efficient CAR expression and demonstrates strong clinical activity with a well-tolerated safety profile, showing minimal CRS and no delayed neurotoxicities, reinforcing its potential in R/R multiple myeloma treatment. Anito-cel stands out in the competitive CAR-T landscape of R/R multiple myeloma through its unique D-Domain binder, enabling high CAR expression and efficient transduction. Compared to CARVYKTI, a marketed BCMA-targeted CAR-T, Anito-cel demonstrates a more favorable safety profile, with notably lower rates of severe CRS and neurotoxicity such as ICANS. While CARVYKTI shows high efficacy, it is often limited by manufacturing complexity, longer turnaround times, and a higher incidence of neurologic adverse events including delayed toxicities.

The termination of Descartes-11, an mRNA-based CAR-T therapy in Phase II trials for high-risk multiple myeloma, may signal challenges in the viability and durability of transient CAR-T platforms. In contrast, the continued progress of Anito-cel, with its durable, single-dose efficacy and favorable safety profile, strengthens its position as a more reliable and promising alternative.