Immunosuppression and Immunotargeted Therapy in Acute Myeloid Leukemia - The Potential Use of Checkpoint Inhibitors in Combination with Other Treatments.

Abstract

Immunotherapy by using checkpoint inhibitors is now tried in the treatment of several malignancies, including Acute Myeloid Leukemia (AML). The treatment is tried both as monotherapy and as a part of combined therapy. Relevant publications were identified through literature searches in the PubMed database. We searched for (i) original articles describing the results from clinical studies of checkpoint inhibition; (ii) published articles describing the immunocompromised status of AML patients; and (iii) published studies of antileukemic immune reactivity and immunotherapy in AML. Studies of monotherapy suggest that checkpoint inhibition has a modest antileukemic effect and complete hematological remissions are uncommon, whereas combination with conventional chemotherapy increases the antileukemic efficiency with acceptable toxicity. The experience with a combination of different checkpoint inhibitors is limited. Thalidomide derivatives are referred to as immunomodulatory drugs and seem to reverse leukemia-induced immunosuppression, but in addition, they have direct inhibitory effects on the AML cells. The combination of checkpoint targeting and thalidomide derivatives thus represents a strategy for dual immunotargeting together with a direct antileukemic effect. Checkpoint inhibitors are now tried in AML. Experimental studies suggest that these inhibitors should be combined with immunomodulatory agents (i.e. thalidomide derivatives) and/or new targeted or conventional antileukemic treatment. Such combinations would allow dual immunotargeting (checkpoint inhibitor, immunomodulatory agents) together with a double/triple direct targeting of the leukemic cells.