A greater knowledge of the molecular pathogenesis of acute myeloid leukemia (AML) has led to the identification of a number of potential therapeutic targets and possibly even personalized therapy. Nonetheless, there remain significant challenges to overcome, according to a review published in Hematological Oncology.

For more than 3 decades, the combination of an anthracycline given for 3 days with continuous infusion of cytarabine for 7 days (3 + 7) has been the standard induction regimen for patients with AML. However, within a few years, the classic 3 + 7 combination may represent undertreatment for most newly diagnosed patients.

“This a very exciting time for AML. We have different new drugs, and we have to learn how to introduce them in the daily practice,” said coauthor Felicetto Ferrara, MD, of the division of hematology at Cardarelli Hospital in Italy, in an interview with Hematology Advisor.

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He added that new treatment agents may lead to better quality of life and improved survival, but the optimal combination of therapies is unknown. “[We are] absolutely in a new era. Combinations of chemotherapy with new agents are expected to become the new standard within a few months,” Dr Ferrara said. “However, there are no clear-cut criteria, and hematologists should make an effort to standardize their approach.”

Barriers Complicating Treatment

Historically, AML has been perceived as a medical emergency requiring immediate intensive chemotherapy, though many patients can wait up to a week while receiving supportive treatment in order to undergo cytogenetic testing, noted the authors. Moreover, meaningful improvements in AML outcomes in the past 2 decades have mainly arisen due to advances in supportive care or allogeneic stem cell transplantation, not the introduction of new, more effective therapeutic agents.

The authors noted that age is still the most important tool for determining the intensity of treatment given to the patient and the patient’s eligibility for stem cell transplantation. However, age brackets are hard to define; for instance, the definition of “elderly” ranges from 55 to 65 years across studies. Clinicians must take into account other patient-specific factors as well when considering initial treatment and may need to counsel patients about the possibility of the initial treatment regimen involving experimental approaches.

Geoffrey Uy, MD, associate professor of medicine at Siteman Cancer Center at Washington University School of Medicine in St Louis, Missouri, said it has now been 45 years since the initial report of 3 + 7 in AML, and its demise has been predicted for a similar time period. However, a significant proportion of patients with AML do not have a targetable mutation. In addition, clinicians often need to treat with incomplete information, as next-generation sequencing assays and cytogenetics can take 1 to 2 weeks to return results.