Multi-year long-term remissions following a single infusion of vispa-cel in second-line large B cell lymphoma patients: A case series from the ANTLER trial
Introduction: Vispacabtagene regedleucel (vispa-cel, formerly CB-010) is an allogeneic anti-CD19 CAR-T cell therapy manufactured from healthy donor T cells. The Cas9 chRDNA genome-editing technology is used for three genome edits: (1) knockout (KO) of the TRAC gene to reduce the risk of graft-versus-host disease (GvHD), (2) insertion of a CD19-specific CAR (FMC63 scFv, 4-1BB), and (3) KO of PD-1 to prevent premature CAR-T cell exhaustion and potentially enhance antitumor activity. Vispa-cel has been optimized through the selection of young donors (< 30 years of age) and HLA matching of two or more alleles between donor and patient. Vispa-cel was evaluated in the ANTLER phase 1 trial (NCT04637763) for patients with r/r B-NHL. Here we present a case series of three patients with second-line (2L) LBCL who achieved durable responses and remain in complete response (CR) at 24 months or longer following a single infusion of vispa-cel without subsequent therapy.
Materials and Methods/Case Presentation/Objective:
Methods: Following progression after prior treatment, all 3 patients enrolled into the ANTLER trial and received lymphodepletion of sequential cyclophosphamide (60 mg/kg/day x 2 days) then fludarabine (25mg/m2/day x 5 days) followed by a single infusion of vispa-cel (80x106 CAR-T cells).
Patient Case 1: A 66-year-old male diagnosed with DLBCL in March 2022 received R-CHOP chemoimmunotherapy (rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone) and experienced disease progression in July 2022.
Patient Case 2: A 66-year-old male diagnosed with DLBCL in August 2021 received R-CHOEP chemoimmunotherapy (R-CHOP plus etoposide) and experienced disease progression in January 2022.
Patient Case 3: A 63-year-old male diagnosed with HGBL in March 2023 received a regimen of rituximab in combination with doxorubicin, etoposide, vincristine, cyclophosphamide, and methotrexate. The patient experienced disease progression in August 2023.
Results/Description/Main Outcome Measure(s):
Results: Following a single infusion of vispa-cel, none of the 3 patients experienced dose-limiting toxicities, GvHD, neurotoxicity, or ≥Grade 3 cytokine release syndrome. PET-CT imaging in Patient Case 1 demonstrated a PR at Day 28 and Month 3, converting to a CR at Month 6. The patient remains in CR beyond 36 months. Patient Case 2 achieved a PR at Day 28, converting to a CR at Month 21, and remains in CR beyond 36 months. Patient Case 3 demonstrated stable disease at Day 28, converting to a PR at Month 12 and a CR at Month 18, with an ongoing CR at the 24-month assessment. All 3 patients demonstrated robust CAR-T cell expansion in the peripheral blood, peaking 7-10 days after infusion and becoming undetectable by approximately 28 days.
Conclusion(s).:
Conclusions: Vispa-cel is an allogeneic CAR-T cell therapy that has demonstrated durable long-term remissions and safety comparable to approved autologous CAR-T cell therapies in 2L LBCL. These 3 patient cases illustrate durable CRs at 24 months or longer with a manageable safety profile. A phase 3 pivotal trial (ANTLER-3) is planned in 2L LBCL patients who are transplant-ineligible and not a candidate or ineligible for autologous CAR-T cell therapy.
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