New drug approvals in acute myeloid leukemia: an unprecedented paradigm shift.

New drug approvals in acute myeloid leukemia: an unprecedented paradigm shift. Clin Adv Hematol Oncol. 2019 Oct;17(10):569-575 Authors: Kopmar NE, Estey EH Abstract We are witnessing an unprecedented paradigm shift in the treatment of acute myeloid leukemia (AML). For nearly 4 decades-since the introduction of cytarabine- and anthracycline-based induction chemotherapy in the 1970s-treatment options for patients with AML have remained limited, and outcomes remain poor for the majority of patients, particularly the elderly. Over the past 10 to 15 years, we have better elucidated the genetic and molecular basis of AML, which has led to our current understanding of disease heterogeneity. We now appreciate that numerous distinct disease subtypes exist, each with their own disease characteristics and risk profile. In keeping with this improved understanding, we have seen the introduction of numerous new agents that are mechanistically targeted against a specific mutation, a deranged cellular pathway, and/or a specific AML disease subset. Within the last 3 years alone, the US Food and Drug Administration has approved 8 new targeted agents for the treatment of AML. With their introduction comes a new sense of optimism, along with questions about how to best use these agents. In this article, we discuss the recently approved agents in AML, the rationale behind their development and the trials that served as the basis for their approval, and the implications of the...
Source: Clinical Advances in Hematology and Oncology - Category: Cancer & Oncology Tags: Clin Adv Hematol Oncol Source Type: research

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In conclusion, favorable-risk cytogenetics may improve the clinical outcomes of patients with FLT3-ITD-mutated AML, but adverse-risk cytogenetics may not further worsen the prognosis. Sorafenib combined with chemotherapy may increase the ORR but would not result in a longer OS and RFS. PMID: 31807186 [PubMed]
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Gao M, Pang H, Kim YM, Lu X, Wang X, Lee J, Wang M, Meng F, Li S Abstract Translocation (9;11)(p21.3;q23.3) is one of the most common lysine methyltransferase 2A (KMT2A)-rearrangements in de novo and therapy-related acute myeloid leukemia (AML). Numerous in vitro and in vivo studies have demonstrated that the KMT2A/MLLT3 super elongation complex subunit (MLLT3) fusion gene on the derivative chromosome 11 serves a crucial role in leukemogenesis. Trisomy 9 as a secondary chromosome change in patients with t(9;11) is relatively rare. The present study reported a unique case of AML with a chromosome 9 trisomy ...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Richard-Carpentier G, DiNardo CD Abstract Acute myeloid leukemia (AML) is a heterogeneous malignancy characterized by recurrent genetic, epigenetic, and metabolic abnormalities. As a result of our increasing knowledge of the underlying biology of AML leading to rational drug development, several new targeted agents have been recently added to our therapeutic arsenal. The BCL2 inhibitor venetoclax in combination with low-dose cytarabine (LDAC) or hypomethylating agents (HMAs) is safe and effective in older patients with newly diagnosed AML ineligible for intensive chemotherapy. Glasdegib, a hedgehog pathway...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Authors: Olin RL Abstract Intensive therapies are often medically indicated for older adults with hematologic malignancies. These may include induction chemotherapy for acute myeloid leukemia (AML), as well as autologous hematopoietic cell transplant (autoHCT) and allogeneic hematopoietic cell transplant (alloHCT). However, it is not always clear how to best deliver these therapies, in terms of determining treatment eligibility, as well as adjusting or adding supportive measures to the treatment plan to maximize successful outcomes. Beyond performance status and presence of comorbidities, comprehensive geriatric as...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Authors: Winters A, Gore L Abstract Although almost 90% of children with acute lymphoblastic leukemia (ALL) and ∼60% of children with acute myeloid leukemia are cured with frontline therapy, relapse and chemotherapy resistance are significant challenges that contribute to morbidity and mortality. Even with long-term survival, the acute and chronic burdens of therapy are major issues for patients and families. Long-term side effects occur, including cardiac, endocrinologic, neurcognitive, orthopedic, and psychosocial problems, and healthy survivorship is frequently compromised. With goals of minimizing relapse a...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Authors: Smith CC Abstract Midostaurin and gilteritinib are FLT3 inhibitors that have been recently approved for use in FLT3-mutant acute myeloid leukemia (AML). These approved drugs represent a new standard of care for patients with FLT3 mutations in both the first-line and salvage settings. The success of midostaurin used in combination with induction chemotherapy has prompted exploration of newer, more potent and targeted inhibitors (including gilteritinib) in the first-line setting in combination with chemotherapy. At the same time, the success of gilteritinib and other newer FLT3 inhibitors as monotherapy in t...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
This article reviews the current landscape of antibody-based and cellular immunotherapies under current clinical evaluation with an emphasis on active or soon-to-open phase 1 trials for children with relapsed/refractory AML. PMID: 31808843 [PubMed - in process]
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
i Acute myeloid leukemia (AML), the most common acute leukemia in adults, is a heterogeneous malignant clonal disorder arising from multipotent hematopoietic progenitor cells characterized by genetic and concerted epigenetic aberrations. Core binding factor-Leukemia (CBFL) is characterized by the recurrent reciprocal translocations t(8;21)(q22;q22) or inv(16)(p13;q22) that, expressing the distinctive RUNX1-RUNX1T1 (also known as Acute myeloid leukemia1-eight twenty-one, AML1-ETO or RUNX1/ETO) or CBFB-MYH11 (also known as CBFβ-ΣMMHX) translocation product respectively, disrupt the essential hematopoie...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
In this study, the protein expression of 79 AML blast samples collected from newly diagnosed patients was examined through flow cytometry. Gamma-secretase inhibitors were used in AML mouse xenograft models to evaluate the contribution of Notch pharmacological inhibition to mouse survival. We used univariate analysis for testing the correlation and/or association between protein expression and well-known prognostics markers. All the four receptors (Notch1–4) and some ligands (Jagged2, DLL-3) were highly expressed in less mature subtypes (M0–M1). Notch3, Notch4, and Jagged2 were overexpressed in an advers...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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