Varnimcabtagene Autoleucel in Relapsed or Refractory B Cell Malignancies Open Access

1. Varnimcabtagene autoleucel is a novel autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy with a murine A3B1 binder.

2. Varnimcabtagene autoleucel in a fractionated infusion protocol (10%, 30%, 60%) yielded durable responses and a favorable safety profile.

Varnimcabtagene autoleucel (varnim-cel), an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has demonstrated antitumor activity and toxicity profile consistent with known CAR T-cell-associated adverse effects in patients with relapsed or refractory B-cell malignancies, including B-cell acute lymphoblastic leukemia (B-ALL) and B-cell non-Hodgkin lymphoma (B-NHL). In this phase 2 clinical trial, we evaluated the efficacy and safety of varnim-cel in individuals with relapsed or refractory B-cell malignancies with at least one prior line of therapy. Varnim-cel was administered at dosage range of 0.1x10⁶ to 5x10⁶ CAR-positive T cells/kg. Primary endpoints were safety and overall response rate (ORR), defined as complete remission (CR) or CR with incomplete hematologic recovery (CRi) for B-ALL, and CR or partial response (PR) for B-NHL. Of the 24 patients treated with varnim-cel, day +28 ORR was 92% (22 of 24 patients). Twenty of 24 patients (ORR 83%) demonstrated a clinical response at day +90 (primary endpoint). At a median follow-up of 10.6 months, 10 of 24 patients (42%) maintained a response. Median progression-free survival was 8.9 months. Common treatment-emergent adverse events were: cytopenias (neutropenia 100%, anemia 96% and thrombocytopenia 92%), cytokine release syndrome (CRS) in 16 patients (67%), including one case (4%) of grade ≥3 severity and immune effector cell–associated neurotoxicity syndrome (ICANS), grade 1, in one patient (4%), with no cases of grade ≥3. Varnim-cel induced durable responses in relapsed or refractory B-cell malignancies, with a favorable safety profile and low incidence of severe immune-mediated adverse events. CTRI trial registration #CTRI/2022/03/041162.