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

Author(s): Eva Leufven, Øystein Bruserud*.

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 28 , 2019

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Abstract:

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Acute myeloid leukemia, checkpoint inhibition, chemotherapy, immunotherapy, lenalidomide, targeted therapy.

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VOLUME: 26
ISSUE: 28
Year: 2019
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DOI: 10.2174/0929867326666190325095853
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