FEATURES
Myeloid Malignancies
The Next Frontier for Immunotherapy
Building on the success of chimeric antigen receptor ( CAR ) T-cell therapies in lymphocytic leukemia and certain lymphomas – and the advances seen with checkpoint inhibitors in solid tumors – researchers are aggressively pursuing new immunotherapy agents for myeloid malignancies .
Several knotty challenges accompany the development of immunotherapies for myeloid malignancies , however , including difficulties with tumor-specific antigen – targeting and a hostile marrow microenvironment . Without a suitable target antigen , for example , it is more likely that immune approaches will result in off-target , off-tumor toxicity and reduced antileukemic effectiveness .
“ We are still searching for the ideal acute myeloid leukemia ( AML ) antigen , and there may not be one ,” Naval Daver , MD , from the University of Texas MD Anderson Cancer Center in Houston , told ASH Clinical News .
“ In acute lymphocytic leukemia ( ALL ), the antigens CD19 and CD22 are more or less restricted to the ALL blast population ,” he explained . “ But in AML , antigens such as CD33 and CD123 are expressed on the majority of myeloid blasts and leukemic stem cells ( LSC ) and also are found on normal hematopoietic stem cells ( HSCs ), progenitor cells , and monocytes and macrophages .”
When clinicians target these antigens on AML cells , they also run the risk of killing normal stem and myeloid progenitor cells , “ which can result in prolonged aplasia , profound cytopenia , and other problems ,” Dr . Daver continued . “ In addition , the treatment may stimulate macrophages and monocytes , resulting in early cytokine release syndrome ( CRS ), even before it is able to kill the bulk of the AML cells .”
How far down the pipeline are the various immunotherapeutic approaches for myeloid malignancies ? And what challenges will investigators face as they try to bring these therapies into routine clinical use ? ASH Clinical News spoke with hematologists and immunotherapy trialists for answers .
Ready for a Revolution Myeloid malignancies are a heterogeneous group of clonal disorders , characterized by excessive proliferation , abnormal self-renewal , and / or differentiation defects of hematopoietic cells and myeloid progenitor cells . They include myeloproliferative neoplasms ( MPNs ), myelodysplastic syndromes ( MDS ), and AML .
AML is the most common acute leukemia among U . S . adults and has the highest mortality rate among the major forms of leukemia , accounting for about 1.3 percent of all new cancer diagnoses and 1.8 percent of cancer deaths each year . 1 Standard treatments for AML have changed little since the 1970s : induction chemotherapy to reduce the number of blasts ( most often using the standard 7 + 3 regimen of cytarabine and anthracycline ), followed by consolidation chemotherapy to destroy residual leukemic cells . The cure rate for primary AML is about 35 percent , and that rate decreases with age .
18 Focus on Myeloid Malignancies