The AML treatment landscape is rapidly evolving

After more than 40 years with limited advances in treatment, recent approvals in acute myeloid leukemia (AML) include a new chemotherapy formulation and targeted therapies.1

However, further treatment options and advances in understanding the biology of AML still are needed.

Examples of the many current challenges and unmet needs in AML include:
Improved transplant rates

For some patients with intermediate-risk or poor-risk AML, the best hope for long-term survival may be hematopoietic stem cell transplant, which is associated with significant improvement in overall survival and relapse-free survival in patients who received HSCT compared with those who did not receive HSCT.2 The rapid initiation of a donor search is a critical component in ensuring that eligible patients can undergo transplant.3

 

Improved disease detection with MRD

Minimal (or measurable) residual disease (MRD) refers to the number of leukemic cells beyond morphological detection that may persist after therapy.4 While MRD is monitored in other hematologic malignancies, clinical trials are still needed to understand the role of MRD in prognosis and treatment and determine the standardization of an MRD assay for AML. The validation of such a panel could help refine risk stratification, including the identification of risk factors associated with transplant therapy; assess treatment response; establish a deeper remission status; and guide postremission treatment strategies.4-6

Additional therapies for elderly and/or frail patients

While AML is most frequently diagnosed in people ≥65 years of age, patients of advanced age and/or those who are deemed unsuitable for intensive chemotherapy may have lower tolerance to cytotoxic agents, limiting treatment options.7,8 These patients may be candidates for therapies that are less intensive, including targeted therapeutic agents, low-intensity chemotherapy, and agents in clinical trials.9

Use of combination therapies

As new therapeutic options become available and treatment strategies develop, future treatment options for some patients with AML may involve using 2 or more therapies with different mechanisms of action. Investigations into the clinical validity of certain combinations are ongoing.10

What impact do different mutations have on patient outcomes?

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References
  1. Stone RM. Which new agents will be incorporated into frontline therapy in acute myeloid leukemia? Best Pract Res Clin Haematol. 2017;30(4):312-316.
  2. Koreth J, Schlenk R, Kopecky KJ, et al. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials [published online for public access]. JAMA. 2009;301(22):2349-2361. doi:10.1001/jama.2009.813
  3. Levis M. FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013? [published online for public access]. Hematology Am Soc Hematol Educ Program. 2013;2013:220-226. doi:10.1182/asheducation-2013.1.220
  4. Ravandi F, Walter RB, Freeman SD. Evaluating measurable residual disease in acute myeloid leukemia. Blood Adv. 2018;2(11):1356-1366.
  5. Kottaridis PD, Gale RE, Langabeer SE, Frew ME, Bowen DT, Linch DC. Studies of FLT3 mutations in paired presentation and relapse samples from patients with acute myeloid leukemia: implications for the role of FLT3 mutations in leukemogenesis, minimal residual disease detection, and possible therapy with FLT3 inhibitors. Blood. 2002;100(7):2393-2398.
  6. Schnittger S, Schoch C, Dugas M, et al. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood. 2002;100(1):59-66.
  7. Katz LM, Howell JB, Doyle JJ, et al. Outcomes and charges of elderly patients with acute myeloid leukemia. Am J Hematol. 2006;81(11):850-857.
  8. National Cancer Institute. SEER cancer stat facts: Leukemia—Acute Myeloid Leukemia (AML). https://seer.cancer.gov/statfacts/html/amyl.html. Accessed January 10, 2018.
  9. Finn L, Dalovisio A, Foran J. Older patients with acute myeloid leukemia: treatment challenges and future directions. Ochsner J. 2017;17(4):398-404.
  10. Menghrajani K, Tallman MS. New therapeutic strategies for high-risk acute myeloid leukemia [published online 2017]. Curr Opin Hematol. 2018;25(2):90-94. doi:10.1097/MOH.0000000000000409
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