The effects of treatment delays and dose reductions with 5-azacitidine for patients with myelodysplastic syndrome (MDS) were reported in a recent study published in the British Journal of Haematology. Dose reductions demonstrated limited effects, but early treatment delays showed possible relationships to outcomes.

“The daily dose of 5-azacitidine in patients with MDS has remained constant over the last 15 years,” wrote the researchers in their report. The researchers explained that patients often undergo changes to dosage because of toxicities, and they set out to explore the effects of such changes on patient outcomes.

The study was an analysis of national registry data for 897 patients with MDS who received 5-azacitidine. Outcomes of response, duration of response, survival, and transformation of MDS to acute myeloid leukemia (AML) were evaluated with respect to dose reductions and treatment delays.

Slightly more than half (51.7%) of the total population showed responses of complete remission, partial remission, or hematologic improvement. Remaining patients (48.3%) had stable disease or treatment failure, and they were classified as nonresponders. Less than half (48.2%) of the total patient population remained alive by data cut-off, and survivors had a median time of follow-up of 13.3 months.


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Treatment delays were seen with 30.5% of patients, and dose reductions were reported for 8.2% of patients. Dose reductions generally did not show negative impacts on the measured outcomes. For 16.7% of patients, treatment delays occurred within the initial 2 treatment cycles, and these delays showed an independent link to poorer survival.

Patients who had already achieved responses seemed less affected by the treatment delays they experienced, in terms of survival, continued response, and time to AML transformation.

When treatment delays occurred before best response, the length of the delay was associated with level of response (P =.041). Delays in patients who reached complete remission had lasted a median of 2.8 days/cycle, while delays in those reaching partial remission lasted a median of 3.3 days/cycle, and those achieving hematologic improvement had a median delay of 5.6 days/cycle.

“For the overall prognosis of the patient, it is probably less risky to temporarily reduce the dose of the drug than to impose a long delay to treatment,” the researchers indicated in their report.

Reference

Diamantopoulos PT, Symeonidis A, Pappa V, et al. The effect of 5-azacytidine treatment delays and dose reductions on the prognosis of patients with myelodysplastic syndrome: how to optimize treatment results and outcomes. Br J Haematol. Published online August 30, 2020. doi:10.1111/bjh.17062