Title:Immunosuppression and Immunotargeted Therapy in Acute Myeloid Leukemia - The Potential Use of Checkpoint Inhibitors in Combination with Other Treatments
Volume: 26
Issue: 28
Author(s): Eva Leufven and Øystein Bruserud*
Affiliation:
- Department of Clinical Science, University of Bergen, Jonas Lies vei 87, N-5020 Bergen,Norway
Keywords:
Acute myeloid leukemia, checkpoint inhibition, chemotherapy, immunotherapy, lenalidomide, targeted
therapy.
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.