CMV Triplex Vaccine to Enhance Adaptive NK and T-cell Reconstitution After Autologous Hematopoietic Cell Transplantation

Cytomegalovirus (CMV) reactivation after hematopoietic cell transplantation (HCT) augments adaptive (CD56dimNKG2C+CD57+) natural killer (NK) and CMV-specific T cells, with potential antitumor effects. Our recent work found an association between higher abundance of adaptive NK cells after auto-HCT and lower risk of relapse in patients with multiple myeloma. Triplex vaccine is a recombinant modified vaccinia Ankara expressing immunodominant CMV antigens, which significantly enhanced CMV-specific T-cell immune responses in allo-HCT recipients. We evaluated whether 2 doses of the vaccine after auto-HCT in patients with lymphoma or myeloma improves reconstitution of adaptive NK and CMV-specific T cells. The primary endpoint was the number of adaptive NK cells at day 100 (∼1 month after dose 2) relative to day 28 (before dose 1). We conducted a single-arm phase 2 clinical trial of 20 patients with lymphoma or myeloma undergoing auto-HCT. Two doses of the vaccine were given on days 28 and 56. Adaptive NK cells increased in CMV-seronegative patients (P = .02), a rise that was more substantial than in unvaccinated historical CMV-seronegative cohorts (P = .03 comparing the rise between the 2 cohorts). There was also an increase in both CD4+ and CD8+ CMV-specific T cells in CMV-seronegative patients (P = .01) and CMV-specific CD8+ effector T cells in CMV-seropositive patients (P = .03). Triplex vaccine improved reconstitution of adaptive NK and CMV-specific T cells after auto-HCT in patients with lymphoma and myeloma. Further study is needed to determine the clinical impact of this modulation of immune response.