Journal
CANCER JOURNAL
Volume 28, Issue 1, Pages 43-50Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/PPO.0000000000000573
Keywords
acute myeloid leukemia; CAR-T cells; CD47; checkpoint inhibitors; immune therapies; PD-1; PD-L1; T-cell engagers
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Immune checkpoint inhibitors have shown relatively low objective response rates in AML, but have demonstrated durable stable disease and hematologic improvement in a subset of patients. Novel AML and myelodysplastic syndrome-specific checkpoints, as well as anti-CD47/SIRP alpha therapy, show promising efficacy and safety, particularly in TP53-mutated AML. Other T cell-based immune therapies are also being investigated.
Immune checkpoint inhibitors have been investigated in acute myeloid leukemia (AML) with an intent to harness the immune microenvironment components to generate an immune response against leukemia. Anti-cytotoxic T-lymphocyte-associated antigen 4 and anti-programmed cell death 1/programmed cell death ligand 1 antibodies have been evaluated in combination with low-intensity therapy and cytotoxic chemotherapy, both in the pretransplant and posttransplant settings. Although the objective response rates with programmed cell death 1- and programmed cell death ligand 1-based therapies have been relatively low, durable stable disease and hematologic improvement were noted in a subset of patients, important endpoints in patients with limited therapeutic options. Novel AML and myelodysplastic syndrome-specific checkpoints such as TIM3 antibodies in combination with azacitidine are showing encouraging efficacy, especially durability of response, in ongoing studies. Anti-CD47/SIRP alpha therapy in combination with azacitidine has shown encouraging efficacy and safety in frontline AML, especially in TP53-mutated AML, a population of significant unmet need. Other T cell-based immune therapies are under investigation. T-cell and natural killer cell bispecific and trispecific engagers have shown modest activity in patients with relapsed and/or refractory AML albeit with frequent cytokine release syndrome. Chimeric antigen receptor T-cell therapy showed immense success in many lymphoid malignancies and is being evaluated in AML. Future trials should be designed to select patients based on markers of response and tailor therapies according to predictive biomarkers.
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