Anito-Cel Yields Durable Responses With Manageable Safety in R/R Multiple Myeloma

Anitocabtagene autoleucel (anito-cel) elicited deep responses that appear to be durable in heavily pretreated patients with relapsed or refractory multiple myeloma, according to data from the phase 2 iMMagine-1 study (NCT05396885) presented at the 2025 ASH Annual Meeting.^1,2

At a median follow-up of 15.9 months, patients who received intravenous (IV) anito-cel at a target dose of 115 x 10⁶ CAR+ T cells (n = 117) experienced an objective response rate (ORR) of 96% in evaluable patients, which comprised a very good partial response (VGPR) rate or better of 88% and a stringent complete response (sCR)/complete response (CR) rate of 74%.¹ The median time to first response was 1.0 months (IQR, 1.0-1.9) and the median time to best response was 4.8 months (IQR, 2.1-9.0). The median time to sCR/CR was 3.2 months (IQR, 2.0-9.2).

Additionally, 95% of patients achieved minimal residual disease (MRD) negativity at a sensitivity level of 10^-5; 78% of patients had MRD negativity at a sensitivity level of 10^-6. The median time to MRD negativity at 10^-5 was 1 month (range, 0.9-6.4). MRD negativity was sustained for 6 months or longer in 83% of patients.

“We have such great data for all of these new therapies and BCMA mechanism of action, but in multiple myeloma, I think we need all these therapies. CAR T as a class has been the first group of therapies that actually leads to a functional cure in patients with relapsed or refractory multiple myeloma,” lead study author Krina Patel, MD, MSc, said during the presentation, “I think that [these results] are really exciting but now we have to do better and get more patients into the cure fraction and make sure [the therapies we are using] are tolerable.”

Patel is an associate professor in the Department of Lymphoma/Myeloma in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, in Houston, Texas.

What was the design of the phase 2 iMMagine-1 trial of anito-cel in multiple myeloma?

The open-label registrational study enrolled patients who were at least 18 years of age and diagnosed with relapsed or refractory multiple myeloma that was treated with at least 3 prior lines of therapy, which included proteasome inhibitors, immunomodulatory drugs (iMiDs), and CD38-targeted therapy.^1,2 Patients were also required to be refractory to their last line of therapy, have an ECOG performance status of 0 or 1, and evidence of measurable disease.¹

If patients had plasma cell leukemia or a history of plasma cell leukemia, solitary plasmacytomas without evidence of other measurable disease, or active central nervous system involvement by malignancy, they were not included in the trial.²

After screening and leukapheresis, participants received lymphodepletion chemotherapy comprised of 30 mg/m² of fludarabine and 300 mg/m² for 3 days of cyclophosphamide followed by a single IV infusion of anito-cel at 115 × 10⁶ CAR+ T cells.¹

The trial’s primary end point was ORR per 2016 International Myeloma Working Group (IMWG) criteria, and important secondary end points included sCR/CR rate by 2016 IMWG criteria and ORR in those limited to 3 prior lines of therapy per the same criteria.

What previous data from the trial were reported with anito-cel?

Preliminary data from the study 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 in evaluable patients (n = 38);³ in those who achieved a sCR/CR, the median PFS was slightly higher, at 34.3 months. The median overall survival has not been reached. Notably, comparable efficacy and durable remissions were reported in those with high-risk features, which accounted for 68% of the population. At the time of presentation, the toxicity profile was noted to be predictable and manageable.

What additional data from the trial were shared during the 2025 ASH Annual Meeting?

The data cutoff date for the current analysis was October 7, 2025. Patients had a median age of 64 years (range, 38-78), about half of patients were male (56%), and most were White (77%).¹ ECOG performance statuses for patients were nearly split, with slightly more patients having a status of 1 (54%) compared with 0 (46%). Eighteen percent of patients had extramedullary disease, and 40% had high-risk cytogenetics.

Additionally, the median of prior lines of therapy received was 3, with a range of 3 to 8 prior lines; 56% of patients had received 3 prior lines of treatment. All patients were refractory to their last line of therapy, 87% were triple refractory, and 41% were pentarefractory. Most patients previously underwent autologous stem cell transplant (79%) and received bridging therapy (76%).

A total of 129 patients enrolled and underwent leukapheresis. Eleven patients discontinued due to withdrawal of consent (n = 5), disease progression (n = 4), intercurrent illness (n = 1), investigator decision (n = 1), or myocardial infarction (n = 1). The remaining 118 patients received lymphodepletion, with 1 patient discontinuing due to withdrawn content. A total of 117 patients were dosed with anito-cel.

Additional data showed that PFS rates with the therapy were 93.1% (95% CI, 86.7%-96.5%) at 6 months, 82.1% (95% CI, 73.6%-88.1%) at 12 months, 67.4% (95% CI, 55.4%-76.8%) at 18 months, and 61.7% (95% CI, 48.0%-72.8%) at 24 months. At these respective time points, OS rates were 95.7% (95% CI, 90.0%-98.2%), 94.0% (95% CI, 87.8%-97.1%), 88.0% (95% CI, 78.8%-93.4%), and 83% (95% CI, 70.7%-90.5%). At a median follow-up of 15.9 months (range, 0.3-33.1), the median PFS and median OS were not yet reached.

What was the safety profile of anito-cel?

The safety profile of anito-cel was manageable and predictable, according to Patel. Most patients (95%) either did not experience cytokine release syndrome (CRS) or had this effect resolve within 10 days of infusion. The majority of CRS events were grade 1 (68%); 16% of patients experienced grade 2 CRS. Moreover, 92% of patients did not experience immune effector cell–associated neurotoxicity syndrome; those who did had grade 1 (3%), 2 (4%), or 3 (1%) events. No secondary primary malignancies of T-cell origin were observed. Since the prior report, which had a data cutoff date of May 1, 2025, no new treatment-related or -emergent deaths occurred.

The most common any-grade adverse effects (AEs) experienced with anito-cel included neutropenia (71%), hypogammaglobulinemia (43%), fatigue (37%), hypophosphatemia (32%), headache (30%), nausea (30%), anemia (28%), diarrhea (28%), and thrombocytopenia (26%). Fifty-six percent of patients experienced any-grade infections. Common grade 3 or higher AEs were hematologic and included neutropenia (70%), thrombocytopenia (26%), anemia (25%), and leukopenia (21%).

What’s next for anito-cel in relapsed/refractory multiple myeloma?

The phase 3 IMMagine-3 study (NCT06413498) will compare the safety and efficacy of anito-cel with standard-of-care treatment in patients with relapsed or refractory multiple myeloma who previously received 1 to 3 lines of therapy, including an anti-CD38 monoclonal antibody and an iMiD.^1,4 Primary end points for the trial, which is currently recruiting, include PFS and MRD-negative CR rate at 9 months. Other important secondary end points comprise CR rate, MRD, OS, and safety.

References

1. Patel K, Dhakal B, Kaur G, et al. A phase 2 registrational study of anitocabtagene autoleucel for the treatment of patients with relapsed and/or refractory myeloma: updated results from IMMagine-1. Presented at the 2025 ASH Annual Meeting; December 6-9, 2025; Orlando, FL. Abstract 256.
2. Study of anitocabtagene-autoleucel in relapsed or refractory multiple myeloma (iMMagine-1) (iMMagine-1). ClinicalTrials.gov. Updated November 13, 2025. Accessed December 6, 2025. https://clinicaltrials.gov/study/NCT05396885
3. Freeman CL, Dhakal B, Kaur G, et al. A phase 2 registrational study of anitocabtagene autoleucel for the treatment of patients with relapsed and/or refractory myeloma: preliminary results from IMMagine-1. Blood. 2024;144(1031). doi.org/10.1182/blood-2024-198499
4. A study comparing anitocabtagene autoleucel to standard of care therapy in participants with relapsed/​ refractory multiple myeloma (iMMagine-3). ClinicalTrials.gov. Updated November 25, 2025. Accessed December 6, 2025. https://www.clinicaltrials.gov/study/NCT06413498