Phase 2 Trial Backs Safety, Efficacy of Varnim-Cel in R/R B Cell Malignancies

In new clinical data from the phase 2 IMAGINE trial (CTRI/2022/03/041162), varnimcabtagene autoleucel (IMN-003A; varnim-cel), a novel autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy, induced durable clinical activity with favorable safety in patients with relapsed or refractory (R/R) B cell malignancies.¹

The study in Blood Immunology & Cellular Therapy shows that of 24 patients treated with varnim-cel infusions, the objective response rate (ORR) at 90 days was 83%. Responses were durable, with a median duration of response of 7.9 months; 42% of patients had maintained a response at a median follow-up of 10.6 months.

In terms of survival, the median progression-free survival was 8.9 months; median overall survival was not reached at the time of analysis.

In this trial, varnim-cel demonstrated a manageable safety profile. Overall, the most frequent treatment-emergent adverse events included neutropenia (100%), anemia (96%), and thrombocytopenia (92%).

Safety remains a paramount concern in the administration of CAR T-cell therapies, which are historically associated with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS occurred in 67% of patients; however, the vast majority of these cases were grade 1 or 2. Only 1 grade 3 CRS event was reported in the study population.

Similarly, the incidence of ICANS was notably low. Only 1 patient experienced grade 1 neurotoxicity, which resolved promptly with standard intervention. The absence of high-grade toxicities is a significant finding, as it may allow for the administration of this therapy in a wider range of clinical settings and potentially reduce the need for intensive care unit monitoring, which poses a significant barrier to CAR T-cell adoption in many global regions.

“These results suggest that varnim-cel offers a favorable safety profile compared with other CD19 CAR T-cell therapies, with a potential for achieving long-term efficacy in patients with B-cell malignancies and especially relevant for use in low- and middle-income countries with a huge unmet need,” concluded authors Damodar et al in the publication.¹

Clinical and Global Context

CAR T-cell therapies targeting CD19 have transformed outcomes in R/R B-cell malignancies, but their adoption remains limited outside high-income settings due to complex manufacturing processes, high costs, and the need for specialized infrastructure to manage toxicities.

In many low- and middle-income countries, access to commercially available CAR T-cell products is extremely limited, leaving patients with few curative options after relapse. Against this backdrop, the development of varnim-cel represents an important step toward expanding access to advanced cellular therapies in resource-constrained healthcare systems. Further long-term follow-up and larger phase 2/3 studies will be required to fully characterize the survival benefits and potential late-onset toxicities associated with the agent.

IMAGINE Trial Design and Patient Characteristics

The IMAGINE trial was a multicenter registration study in India evaluating the safety and efficacy of varnim-cel in a cohort of 25 patients with varnim-cel with R/R B cell malignancies, including B-cell acute lymphoblastic leukemia (B-ALL) and B-cell non-Hodgkin lymphoma (B-NHL).² The dual primary end points were safety and ORR, with the latter defined as the proportion of patients who had achieved either complete remission (CR) or CR with incomplete hematologic recovery for B-ALL or partial response for B-NHL.

Patients had received at least 1 line of therapy prior to varnim-cel treatment; the cohort had received a median of 3 prior treatment lines (range, 1-5). The median age of the cohort was 32.5 years (range, 4-66).

REFERENCES

1. Damodar S, Bhat S, Thirumalairaj R, et al. Varnimcabtagene autoleucel in relapsed or refractory B-cell malignancies. Blood Immunology & Cellular Therapy. 2026;2(1):100024. doi:10.1016/j.bict.2025.100024

2. A study to test a new type of treatment for blood cancer. In this new treatment the blood cells of patients are modified to kill cancer cell on their own. Clinical Trials Registry – India. Updated July 28, 2025. Accessed February 5, 2026. https://tinyurl.com/kkxhv9b3