The hypomethylating agents decitabine and azacitidine administered at a low dose is safe and effective for patients with lower-risk myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN), according to results of a recent study published in Blood (December 2017;130:1514-1522).
Both decitabine and azacitidine have demonstrated the ability to improve survival in patients with higher-risk myelodysplastic syndrome. However, their efficacy for lower-risk disease is less known. A general belief exists among hematologists that low doses of these agents administered in shorter treatment durations may be active in lower-risk disease.
Elias Jabbour, MD, associate professor, department of leukemia, University of Texas MD Anderson Cancer Center, and colleagues conducted a study to assess response rates and event-free survival among 113 patients with lower-risk MDS treated with low-dose hypomethylating agents. The phase II study randomly assigned patients to receive decitabine (n = 73; dose, 20 mg/m2) daily for 3 consecutive days or azacitidine (n = 40; dose, 75 mg/m2 ) daily, for 28-day cycles. Patients could receive lower doses of decitabine (15 mg/m2 and 10 mg/m2) and azacitidine (50 mg/m2 and 25 mg/m2) if they experienced grade 3-4 toxicities.
Researchers noted that 81% of patients had intermediate-risk disease, 18% had therapy-related disease, 14% had chronic myelomonocytic leukemia, and 5% had overlapped MDS/MPN other than chronic myelomonocytic leukemia.
After a median follow-up of 20 months, researchers reported an overall response rate of 70% and 49% for patients treated with decitabine and azacitidine, respectively. The overall median event-free survival was 18 months (20 vs 13 months for patients treated with decitabine and azacitidine, respectively).
Additionally, researchers reported that treatment was well tolerated, with a 6-week mortality rate of 0%.
“Our study indicates that the use of hypomethylating agents at low dose is relatively safe, as no treatment-related early deaths or high grade adverse events were encountered,” the researchers wrote. “Whether early intervention with low-dose hypomethylating agent therapy will impact the outcome of these patients remains to be confirmed. Even though promising responses were seen in these lower-risk patients, it is unknown whether this translates to meaningful changes in survival or quality of life, compared to intervening when patients have higher-risk disease.”—Zachary Bessette