Clinical Trial Evaluating DC/AML Fusion Cell Vaccination Alone and in Conjunction with PD-1 Blockade in AML Patients Who Achieve a Chemotherapy-Induced Remission

Abstract

HCT (79 pts) No HCT (38 pts) P-value logistic regression Unfavorable cytogenetics (n) 30 (37%) 7 (18%) 0.18 Secondary AML (n) 39 (49%) 15 (39%) 0.32 Early relapse (n) (>5% marrow blasts within 4.9 months of CR1 (range 0.9-10, median 3.75) 0 (0%) 13 (34%) <0.001 Twenty-four of the 38 (63%) non-HCT patients were HLA-typed and matched donors were found for 13 of these 24 patients (54%; 5 related, 8 unrelated). Seven of the 14 non-typed patients (50%) had financial barriers or refused HLA-typing. Only 2 of these 38 (5%) received HCT beyond CR1. Conclusion: These data suggest that HCT can be performed in CR1 in the majority of high-risk AML patients in whom it is currently recommended. Patients in whom HCT is not done are characterized by a poorer performance status (but not older age) and by early relapse. In the absence of these 2 factors, .75% of patients with high-risk AML under the age of 75 can receive HCT in CR1. A national study is planned to assess the extent to which these results can be generalized.

A blood dendritic cell vaccine for acute myeloid leukemia expands anti-tumor T cell responses at remission

“…Early pre-clinical data has suggested the potential of combining checkpoint blockade with DC therapy in AML, 32 and clinical assessment of PD-1 blockade with a Mo-DCbased vaccine in AML has been undertaken. 33 We demonstrated increased expression of PD-1 and TIM-3 on CD4 C T cells in AML at CR and after ATx. CD4 C T cell help is essential for expanding effective antigen-specific T cell responses.…”

Immune Cells in Cancer Therapy and Drug Delivery

“…Blockade of PD-1 reduced Treg cell numbers attenuating their immunosuppressive activity and also encouraged the ability of DCs to stimulate leukemia antigen-specific T cells [ 85 , 91 ]. Combinatorial therapy of anti-PD-1mAb pidilizumab and DCs vaccination is currently under phase II clinical trial and when used in patients with AML, remission occurs [ 92 ]. Furthermore, clinical trial of PD-L1/2-silenced DC vaccination in combination with donor lymphocyte infusions for the treatment of posttransplant leukemia relapse has also been registered [ 93 ].…”

Dendritic Cells as Pharmacological Tools for Cancer Immunotherapy

“…The observed promotion of antileukemic immunity after interference with the PD-1/PD-L signaling pathway is not only due to enhanced activation of effector T cells but also in part due to reducing T reg cell numbers and attenuating their immunosuppressive activity (Ge et al, 2009;Zhou et al, 2010). A phase II clinical trial investigating the combined use of DC therapy with the anti-PD-1 mAb pidilizumab (CT-011; CureTech, Yavne, Israel) is currently underway in remission patients with AML (Rosenblatt et al, 2011). A clinical trial of PD-L1/ 2-silenced DC vaccination in combination with donor lymphocyte infusions for the treatment of post-transplant leukemia relapse has also been registered (CCMO identifier, NL37318) .…”