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.
Author Info: (1) Division of Oncology, Stanford University, Stanford, CA. (2) Division of Oncology, Stanford University, Stanford, CA. (3) Division of Oncology, Stanford University, Stanford, C
Author Info: (1) Division of Oncology, Stanford University, Stanford, CA. (2) Division of Oncology, Stanford University, Stanford, CA. (3) Division of Oncology, Stanford University, Stanford, CA. (4) Division of Oncology, Stanford University, Stanford, CA. (5) Department of Oncology, University of Alberta, Edmonton, Alberta, Canada. (6) Division of Blood and Marrow Transplantation, Stanford University Healthcare, Stanford, CA. (7) Division of Oncology, Stanford University, Stanford, CA. (8) Division of Oncology, Stanford University, Stanford, CA. (9) Division of Oncology, Stanford University, Stanford, CA. (10) Division of Oncology, Stanford University, Stanford, CA. (11) Division of Oncology, Stanford University, Stanford, CA. (12) Division of Blood and Marrow Transplantation, Stanford University Healthcare, Stanford, CA. (13) Division of Blood and Marrow Transplantation, Stanford University Healthcare, Stanford, CA. (14) Division of Blood and Marrow Transplantation, Stanford University Healthcare, Stanford, CA. (15) Division of Blood and Marrow Transplantation, Stanford University Healthcare, Stanford, CA. (16) Division of Blood and Marrow Transplantation, Stanford University Healthcare, Stanford, CA. (17) Division of Oncology, Stanford University, Stanford, CA. (18) Adaptive Biotechnologies, Seattle, WA. (19) Division of Oncology, Stanford University, Stanford, CA. (20) Division of Oncology, Stanford University, Stanford, CA. (21) Division of Oncology, Stanford University, Stanford, CA. (22) Department of Surgery, Stanford University Healthcare, Stanford, CA. (23) Icahn School of Medicine at Mount Sinai, New York, NY. (24) Division of Oncology, Stanford University, Stanford, CA.
