Frank et al. report the safety and efficacy of a CpG-activated autologous tumor cell vaccine, the harvest of vaccine-primed T cells, and adoptive transfer following autologous stem cell transplant (ASCT) in mantle cell lymphoma patients. All trial-related treatments were well tolerated and 89% (40/45) patients were negative for minimal residual disease1 year after ASCT. In 40% of patients, vaccination induced expansion of antitumor CD137+CD8+ memory T cells, which correlated with longer progression-free survival. Patients with high PD-L1 expression on the tumor following CpG exposure showed shorter times to progression and shorter overall survival.
Contributed by Shishir Pant
ABSTRACT: Here, we report on the results of a phase I/II trial (NCT00490529) for patients with mantle cell lymphoma who, having achieved remission after immunochemotherapy, were vaccinated with irradiated, CpG-activated tumor cells. Subsequently, vaccine-primed lymphocytes were collected and reinfused after a standard autologous stem cell transplantation (ASCT). The primary endpoint was detection of minimal residual disease (MRD) within 1 yr after ASCT at the previously validated threshold of >/=1 malignant cell per 10,000 leukocyte equivalents. Of 45 evaluable patients, 40 (89%) were found to be MRD negative, and the MRD-positive patients experienced early subsequent relapse. The vaccination induced antitumor CD8 T cell immune responses in 40% of patients, and these were associated with favorable clinical outcomes. Patients with high tumor PD-L1 expression after in vitro exposure to CpG had inferior outcomes. Vaccination with CpG-stimulated autologous tumor cells followed by the adoptive transfer of vaccine-primed lymphocytes after ASCT is feasible and safe.