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Emerging immunotherapies in older adults with acute myeloid leukemia.

ABSTRACT: We summarize recent advances for acute myeloid leukemia (AML) in older patients, with a focus on immunotherapeutics. Although the recently updated US SEER data still show that the majority of older AML patients do not receive any therapy, this reality is slowly changing. Advances in our understanding of the biology of AML and in the field of immunology are facilitating the development of alternative therapeutic options for patients, affording more and novel opportunities for potentially curative treatment.Data from multiple cooperative groups show that older patients benefit from the incorporation of gemtuzumab ozogamicin, an anti-CD33 mAb toxin, into induction regimens. The first prospective study for reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation in older AML patients was reported at the American Society of Hematology Annual Meeting, 2012; the approach was feasible and improved disease-free survival over conventional chemotherapy. Proof-of-concept trials targeting specific antigens such as WT1 or novel unique leukemia-associated antigens are currently underway, as well as other trials using chimeric antigen receptor T cells or (natural killer/effector cells in nontransplantation settings.Wider application of immunotherapies such as allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning have altered the landscape and offer potential for cure of an increasing number of older AML patients.

SUBMITTER: Vasu S

PROVIDER: S-EPMC4083702 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Emerging immunotherapies in older adults with acute myeloid leukemia.

Vasu Sumithira S Blum William W

Current opinion in hematology 20130301 2

<h4>Purpose of review</h4>We summarize recent advances for acute myeloid leukemia (AML) in older patients, with a focus on immunotherapeutics. Although the recently updated US SEER data still show that the majority of older AML patients do not receive any therapy, this reality is slowly changing. Advances in our understanding of the biology of AML and in the field of immunology are facilitating the development of alternative therapeutic options for patients, affording more and novel opportunitie ...[more]

PMID: 23334192

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Project description:Acute myeloid leukemia (AML) is a hematologic malignancy that carries a poor prognosis and has garnered few treatment advances in the last few decades. Mutation of the internal tandem duplication (ITD) region of fms-like tyrosine kinase (FLT3) is considered high risk for decreased response and overall survival. Midostaurin is a Type III receptor tyrosine kinase inhibitor found to inhibit FLT3 and other receptor tyrosine kinases, including platelet-derived growth factor receptors, cyclin-dependent kinase 1, src, c-kit, and vascular endothelial growth factor receptor. In preclinical studies, midostaurin exhibited broad-spectrum antitumor activity toward a wide range of tumor xenografts, as well as an FLT3-ITD-driven mouse model of myelodysplastic syndrome (MDS). Midostaurin is orally administered and generally well tolerated as a single agent; hematologic toxicity increases substantially when administered in combination with standard induction chemotherapy. Clinical trials primarily have focused on relapsed/refractory AML and MDS and included single- and combination-agent studies. Administration of midostaurin to relapsed/refractory MDS and AML patients confers a robust anti-blast response sufficient to bridge a minority of patients to transplant. In combination with histone deacetylase inhibitors, responses appear comparable to historic controls, while the addition of midostaurin to standard induction chemotherapy may prolong survival in FLT3-ITD mutant patients. The response of some wild-type (WT)-FLT3 patients to midostaurin therapy is consistent with midostaurin's ability to inhibit WT-FLT3 in vitro, and also may reflect overexpression of WT-FLT3 in those patients and/or off-target effects such as inhibition of kinases other than FLT3. Midostaurin represents a well-tolerated, easily administered oral agent with the potential to bridge mutant and WT-FLT3 AML patients to transplant and possibly deepen response to induction chemotherapy. Ongoing studies are investigating midostaurin's role in pretransplant induction and posttransplant consolidation therapy.

Dataset Information

Emerging immunotherapies in older adults with acute myeloid leukemia.

Publications

Emerging immunotherapies in older adults with acute myeloid leukemia.

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