Next Generation CAR T For Myeloma: Deepening Results & Efficacy
- Updated phase II iMMagine data suggest anito-cel could reset expectations for BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma. Anito-cel is an experimental CAR T-cell therapy for relapsed/refractory multiple myeloma patients
- The study demonstrates deepening responses, high MRD-negativity rates, and manageable toxicity in a heavily pretreated population.
- In updated trial results, anito-cel demonstrated an overall response rate of 97% and a complete response rate of 68%.
- Several therapies are available in this space. Anito-cel offers robust efficacy together with a reassuringly favorable safety profile, making it an important addition to current CAR T options
Anito-cel, an investigational BCMA-directed CAR T-cell therapy, is demonstrating compelling efficacy and a favorable safety profile in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM), according to updated phase II data from the iMMagine study, which were presented at ASH 2025 Annual Meeting.
Dr. Krina Patel, the Myeloma Section Chief at MD Anderson Cancer Center who led the study, tells SurvivorNet Connect that the research is providing tangible results for patients who would be considered “vulnerable.”
Study Design & Patient Population
The iMMagine trial is a pivotal phase II study evaluating anito-cel for potential FDA approval. The study enrolled 117 patients who underwent apheresis followed by lymphodepleting chemotherapy and CAR T-cell infusion. Eligible patients were heavily pretreated, having received at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and anti-CD38 therapy, and were refractory to their last line of therapy.
“Patients in this study are what we would consider a vulnerable myeloma population,” Dr. Patel explains. “Despite this, 99% of patients had successfully manufactured cells, demonstrating the feasibility of anito-cel even in heavily pretreated patients.”
The median dose infused was approximately 115 million CAR T-cells, distinguishing anito-cel from other BCMA-directed CAR T therapies, which often require higher cell numbers.
“The way that this CAR T works is it has something called a D-domain,” Dr. Patel explains. “Because it’s a small protein, we think it makes it easier to manufacture the CAR T and results in more efficient CAR transduction.”
This design produces a higher proportion of CAR-positive T-cells, enhancing tumor cell targeting and cytotoxicity even with fewer total infused cells.
“We also think that the way it comes off the myeloma cell and off the target fast is probably why there might be less toxicity, in terms of CRS or ICANS or delayed inflammation. This is one of the features that differentiates anito-cel from other BCMA CAR Ts,” Dr. Patel adds.
Efficacy Outcomes
The updated phase II analysis demonstrates high response rates with durable activity.
- Overall Response Rate (ORR): 96-97%
- Complete Response (CR) Rate: 68-74%
- MRD Negativity: >95% at 10-5, with 83% of patients maintaining MRD negativity beyond six months
“These numbers are very encouraging,” Dr. Patel says. “We are seeing ongoing deepening of responses over time, which suggests that progression-free survival (PFS) may be substantial in this patient population.”
Current calculations estimate the 24-month PFS at 61.7%, though median PFS and overall survival have not yet been reached, reflecting both the potency and durability of the therapy.
Safety Profile
Anito-cel has demonstrated a manageable toxicity profile in heavily pretreated RRMM patients. Cytokine release syndrome (CRS) occurred in approximately 84% of patients, predominantly grade 1-2, with only 5% experiencing grade ≥3 CRS. Neurotoxicity (ICANS) was observed in 17% of patients, with grade ≥3 events in 3%.
These rates are lower than what has been reported for other BCMA-directed CAR T therapies, consistent with the hypothesized benefit of the rapid D-domain disengagement from target cells, which may limit excessive immune activation.
Study Limitations & Next Steps
While iMMagine demonstrates impressive activity, the study is single-arm without a comparator, making it difficult to directly contextualize efficacy or toxicity against existing therapies. Follow-up is still relatively short, and median PFS and OS have not been reached, leaving long-term durability and late toxicities uncertain.
Subgroup analyses such as outcomes by cytogenetic risk, age, extramedullary disease, or prior BCMA exposure have not been fully reported, limiting our understanding of which patients may derive the greatest benefit. Further follow up and phase III study will be critical to define the full clinical potential of anito-cel, its optimal patient population, and its role earlier in the treatment paradigm.
Following these promising phase II results, a phase III study is already underway, evaluating anito-cel in patients with one to three prior lines of therapy, compared with current standard-of-care options.
“Our next step is our phase III trial, which is already open,” Dr. Patel said. “We hope that this study will support the use of anito-cel in earlier relapses, and eventually, allow us to move the best therapies upfront to improve outcomes and maybe even the functional cure rate for our myeloma patients.”
Anito-cel represents a differentiated CAR T option in multiple myeloma, combining high response rates, durable MRD-negative remissions, and a favorable safety profile. As the therapy advances into phase III trials in earlier lines, it may redefine the treatment paradigm, bringing highly effective cellular therapy closer to diagnosis while continuing to clarify its optimal patient population and long-term benefit.
