Real-world experience with varnimcabtagene autoleucel (murine CD19 CAR-T) from India: A step towards enhanced patient access with excellent safety and efficacy

Abstract Background: Varnimcabtagene autoleucel (IMN-003A), an autologous second-generation CAR T-cell product with a 4-1BB co-stimulatory domain and murine A3B1 binder, was approved in India in February 2024 for B-cell Non-Hodgkin's Lymphoma above 18 years based on safety and efficacy data (ASH 2022, 2023). In this observational study, we present real-world experience (RWE) on the access, safety, and efficacy of the commercial use of this product across multiple clinical centres in India. Methods: Patients (pts) with r/r B-NHL aged 18+ years infused with varnim-cel as standard of care in a fractionated infusion protocol (10%/30%/60%) at target dose 5x106/kg CAR+ cells after Flu-Cy lymphodepletion regimen from 02 August 2024 till 15 July 2025 were included in this study. No adjuvant or maintenance treatment was administered. Ten centres across India were trained on clinical management and toxicity algorithms prior to initiation of treatment. Apheresis and infusion scheduling based on patient priority along with manufacturing was done centrally from a single facility. Manufacturing parameters such as manufacturing success rate (MSR), vein to vein (leukapheresis to infusion) and brain-to-vein time (pt registration to infusion) were evaluated. Response was assessed as per IWG (B-NHL) criteria. Adverse events (AEs) including CRS, ICANS and IEC-HS were analysed as per published criteria. Results: As of data cut-off, 30 pts with B-NHL underwent leukapheresis (median age 58 yrs, range 21 to 79; Gender: Male 63%, Female 37%; Ethnicity: Asians 100% (Indians 83%, Bangladeshi 3%, Nepali 3%, Mauritian 3%, Arab 7%) across 10 centres in India. Disease characteristics included: Subtypes - Diffuse Large B-cell Lymphoma: 67%, Primary Mediastinal Large B-cell Lymphoma: 3%, T-cell / Histiocyte Rich Large B Cell Lymphoma: 3%, Transformed Indolent: 7%, Follicular Lymphoma: 10%, Mantle Cell Lymphoma: 10%; Extranodal involvement 83%; Bulky disease 37%; CNS involvement 7% with previous lines of treatment – median 3; range 1 to 5. One pt had undergone previous autologous transplant. Centralized manufacturing ensured all patients received apheresis and manufacturing slots within a median of 6 days (range 1 to 29). Second apheresis was done in 2 patients (inadequate cell count – 1; sterility failure – 1). Temperature control for varnim-cel was uniformly maintained ≤ -150 C using ultracold chain logistics. Of the 30 pts, 23 patients have been infused (pt death before infusion - 1; product not manufactured -1; and 5 patients awaiting infusion), all pts received fractionated infusions, majority were on Days 0, +3, +7 and 17 pts (57%) underwent bridging therapy. Median CAR-T cell manufacturing time was 26 days (range 14 to 41) with 96% MSR (1 batch terminated). Median distance travelled by pts to access varnim-cel was 493 Km (range 11 to 6797). Median brain-to-vein time was 45 days (range 27 to 70). Median vein-to-vein time was 34 days (range 23 to 63). The B2V and V2V were not influenced by distance of the treatment centres to the manufacturing site. Of the 19 evaluable pts at D+28, overall response rate (ORR) was 79% (15/19) with 53% in CR. Ten pts were evaluable at D+90 with an ORR of 60% (6/10). 4 pts relapsed by D+90. ORR in Median progression-free survival and overall survival were not reached. RWE efficacy outcomes concur with the pivotal Phase II study (IMAGINE): 92% ORR at D+28 in both B-ALL and B-NHL cohorts. AESIs reported were CRS (overall 48%; G3+ 4%); ICANS (overall 9%; G3+ 4%); Neurotoxicity (overall 4%); Immune Cell Associated Haemato-Toxicity (ICAHT) - neutropenia (overall 48%; G3+ 26%); anemia (overall 70%; G3+ 13%); and thrombocytopenia (overall 57%; G3+ 9%). CRS median onset was D+3 and duration 3 days. Tocilizumab, steroids and anakinra usage was in 39%, 9% and 4% respectively. RWE safety profile is similar to the pivotal Phase II study (IMAGINE): CRS (overall 67%; G3+ 4%); ICANS (overall 4%; G3+ 0%) and ICAHT - neutropenia (overall 100%; G3+ 92%); anemia (overall 96%; G3+ 29%); and thrombocytopenia (overall 92%; G3+ 21%) with no additional safety signals.Conclusion: The real-world experience provides strong evidence of efficacy and safety of varnim-cel in B-NHL comparable with pivotal study. It also proves the robustness of trans-national ultracold chain logistics, safe and effective clinical delivery and management systems for commercial rollout across multiple centres in India to provide equitable access in South Asia.