Patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) who are excluded from conventional clinical trials because of comorbid conditions may benefit from participation in trials of low-intensity interventions, a new study’s findings indicate.
“Most clinical studies for AML and MDS exclude patients with comorbidities, active or recent malignancies of other types, organ dysfunction, or poor performance status,” said Guillermo Garcia-Manero, M.D., a professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. “But how these criteria protect patients is unclear. Although some are based on clinical reasoning, it seems that some criteria are in place more to protect the drug or intervention being studied rather than the patient.”
Dr. Garcia-Manero and his colleagues sought to determine whether patients who would be excluded from conventional studies for the reasons listed above could be treated in a clinical trial. The two-phase study included stopping rules for survival, response, and toxicity.
In the initial single-arm phase of the study, 30 patients (16 with MDS and 14 with AML) received low doses of azacitidine plus vorinostat. The overall and complete response rates were 40% and 27%, respectively; the 60-day overall survival rate was 83%; and the median overall survival and event-free survival durations were 7.8 and 5.1 months, respectively. The main adverse events were grade 1 or 2 gastrointestinal toxic effects.
In the subsequent randomized phase of the study, 79 patients (47 with MDS and 32 with AML) received low doses of either azacitidine alone (27 patients) or azacitidine plus vorinostat (52 patients). The monotherapy and combination therapy groups’ 60-day survival rates (67% and 85%, respectively), overall response rates (48% and 46%, respectively), overall survival durations (6.1 and 7.6 months, respectively), and event-free survival durations (3.0 and 5.5 months, respectively) did not differ significantly. Again, the main adverse events were grade 1 or 2 gastrointestinal toxic effects, which occurred more frequently in the combination therapy group (81%) than in the single-therapy group (56%).
A univariate analysis revealed that a performance score of 3 or more, a creatinine or bilirubin concentration of 2 mg/dL or more, and the presence of another malignancy did not adversely affect 60-day survival, overall survival, or event-free survival. In addition, an Adult Comorbidity Evaluation-27 index score of 2 or 3 did not reduce survival duration.
Dr. Garcia-Manero and his colleagues concluded that the standard exclusion criteria used in clinical trials for AML and MDS patients should be re-evaluated. According to the team, relaxing the criteria could make experimental agents available to the patients whose poor prognoses make them the most likely to benefit.
The results of the study were presented in December at the 58th Annual Meeting of the American Society for Hematology.
OncoLog, January 2017, Volume 62, Issue 1