NCCN Acute Myeloid Leukemia Updates

Every year more than 13,000 cases of acute myeloid leukemia (AML) are diagnosed and almost 9000 individuals die of this disease. At the National Comprehensive Cancer Network (NCCN) 15th Annual Meeting, B. Douglas Smith, MD, The Sidney Kimmel Comprehensive Cancer Center at John's Hopkins, presented updates to the NCCN Acute Myeloid Leukemia Guidelines, which now emphasize using risk stratification to assist in selecting treatment for AML patients and have been expanded to distinguish the therapy options for acute promyelocytic leukemia (APL) patients. “AML is a disease of older patients, presenting a clinical challenge for physicians since advances in therapy have been limited,” noted Smith in a press release.

The best indicator of response is cytogenetics, as certain cytogenetic abnormalities are associated with very good outcomes, whereas others are associated with a poor prognosis and a high risk of relapse following treatment. According to Smith, however, approximately 50% of all AML patients have “normal” cytogenetics and fall into an intermediate-risk group. In these patients, the use of molecular markers may be especially important, as traditional testing does not provide insight into their disease and prognosis. One of the molecular markers he discussed was the FLT3-ITD mutation, which has a poor prognosis, unless it is the wild type, whereas another mutation, NPM1, carries a better prognosis unless it is the wild type. Smith noted that sometimes the FLT3-ITD and NPM1 mutation may be found in combination, and while targeting mutations such as these, most notably FLT3-ITD, has not been successful as of yet, there is promise for the future, and, for the time being, their presence can give an indication of a patient’s prognosis.

One important prognostic indicator that Smith discussed was white blood cell (WBC) count at presentation. He noted that these counts, which may assist with treatment selection, may be especially important for patients found to have APL, which is the most curable subtype of AML. “If physicians can better define the prognosis of an individual patient’s APL, they can more accurately develop a tailored treatment plan for the patient,” said Smith. “This may even allow physicians to decrease the total amount of treatment a patient receives while maintaining positive outcomes,” stressing that “lower risk disease can have good outcomes with less treatment, resulting in better long-term outcomes.”

The NCCN Guidelines now distinguish the therapy options for APL patients with low-risk or high-risk disease using their WBC count status, recommending assessing WBC count prior to therapy in those who can tolerate anthracycline therapy. Those found to have a WBC count ≥10,000 are considered to be low/intermediate risk, whereas those with a count <10,000 are considered high risk. A platelet count <40,000 at presentation is another poor risk feature. A strong recommendation in the NCCN Guidelines is that APL should be treated according to one of the regimens established from clinical trials. “The panel strongly emphasizes the importance of using these regimens consistently and not mixing induction from one with consolidation from the other,” said Smith, and told the audience to “pick one protocol and stick to it.”

Smith also noted that the treatment of AML in individuals 60 years and older continues to be challenging, stating that “many will die from their leukemia.” Because the long-term survival rates of these patients have not improved, the updated NCCN Guidelines recommend that patient performance status, adverse features, comorbid conditions, and chronological age must be considered when selecting treatment, which has received some additions. The NCCN updates now include 5-azacytidine (Vidaza) and decitabine (Dacogen) as low-intensity treatment options and clofarabine (Clolar) as an intermediate-intensity treatment option in patients 60 years and older; these agents have a category 2B designation. He also noted that “some patients will have a good response [to treatment], and if they respond, they will do OK regardless of age.”

Smith concluded the presentation by emphasizing the importance of ongoing clinical trials in improving AML outcomes and noted that there are several areas in the NCCN Guidelines where referral to a clinical trial is recommended.

To review the full NCCN Guidelines, including AML, visit the NCCN website.