Using risk stratification to assist in treatment selection was just one of the focal points at a recent presentation of the NCCN Clinical Practice Guidelines for Oncology (NCCN Guidelines™) for Acute Myeloid Leukemia (AML) at the NCCN 15th Annual Conference. B. Douglas Smith, MD of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and a member of the NCCN Guidelines Panel for AML, spoke about the challenges in treating AML as well as recent updates to the NCCN Guidelines™.
“Due to little progress being made in long-term survival rates of these patients, the NCCN Guidelines recommend that patient performance status, in addition to adverse features, comorbid conditions, and a patient’s chronological age, need to be considered when selecting treatment”
Dr. Smith began with an overview on the demographics of AML stating that there are more than 13,000 cases diagnosed annually and that incidence exponentially increases with age.
“AML is a disease of older patients presenting a clinical challenge for physicians since advances in therapy have been limited. Unfortunately, many adults with acute leukemia, will die from their acute leukemia,” said Dr. Smith.
Among prognostic factors in AML, cytogenetics, the chromosomal structure of the leukemic cell, remains important.
“Cytogenetic analysis performed at diagnosis is widely recognized as one of the most valuable prognostic indicators in AML. However, there is now evolving data to support several important molecular markers that may further define a patient’s prognosis,” said Dr. Smith.
Certain cytogenetic abnormalities are associated with very good outcomes, while a number of other abnormalities are known to associate with a poor prognosis and a high risk of relapse after treatment. About half of all AML patients have “normal” cytogenetics and fall into an intermediate risk group.
“Molecular markers are especially important to patients with normal cytogenetics as traditional testing does not provide much insight into their disease,” said Dr. Smith.
Dr. Smith pointed to a portion of the NCCN Guidelines that detail risk status based on cytogenetics and molecular abnormalities.
Dr. Smith discussed additional updates to the most recent version of the NCCN Guidelines including the addition of risk stratification, based on white blood cell (WBC) count to assist with the selection of treatment for patients with acute promyelocytic leukemia (APL), 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.”
The NCCN Guidelines were expanded to distinguish the therapy options for APL patients with low risk or high risk disease as defined by WBC count status. The NCCN Guidelines recommend that patients with APL who can tolerate anthracycline therapy should have their WBC count assessed prior to therapy to classify them as high risk, which constitutes having a WBC count greater or equal to 10,000, or low/intermediate risk, which is having a WBC count of less than 10,000.
Smith stressed, “The NCCN Guidelines state 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.”
The treatment of AML in the elderly (>60 years) continues to be an unmet need and a challenge Dr. Smith noted.
“Due to little progress being made in long-term survival rates of these patients, the NCCN Guidelines recommend that patient performance status, in addition to adverse features, comorbid conditions, and a patient’s chronological age, need to be considered when selecting treatment,” said Dr. Smith.
Additional therapies were recently added to the NCCN Guidelines based upon clinical trial results including 5-azacytidine (Vidaza®, Celgene Corporation) and decitabine (Dacogen®, Eisai Inc.), as low intensity treatment options and clofarabine (Clolar®, Genzyme Corporation) as an intermediate intensity treatment option for patients with AML who are 60 years or older. All these agents have a category 2B designation.
In conclusion, Dr. Smith emphasized that ongoing clinical trials are critically important for continued advancements in AML noting several occurrences in the NCCN Guidelines that recommend referral to a clinical trial.
The NCCN Guidelines are developed and updated through an evidence-based process with explicit review of the scientific evidence integrated with expert judgment by multidisciplinary panels of physicians from NCCN Member Institutions. The most recent version of this and all the NCCN Guidelines are available free of charge at NCCN.org.
National Comprehensive Cancer Network