Discontinuation of hypomethylating agent therapy in patients with myelodysplastic syndromes or acute myelogenous leukemia in complete remission or partial response: Retrospective analysis of survival after long-term follow-up

• We studied outcomes in rare patients who discontinue HMA therapy while in response.
• Early discontinuation of HMA is associated with poor survival.
• >12 therapy courses and non-high-risk cytogenetics were significant predictors of survival.

Hypomethylating agents (HMA), such as 5-azacitidine or decitabine, are currently used to treat patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) until treatment failure. However, the outcomes for patients who discontinue therapy after achieving partial response (PR) or complete remission (CR) but before treatment failure have not been reported. We present a series of 16 patients with higher-risk MDS (n = 5; 31%) or AML (n = 11; 69%) who achieved PR (n = 1) or CR (n = 15) and stopped HMA therapy while in response in the context of clinical trials. They received a median of 12 courses (range 1–24) and achieved response after a median of 1 course of therapy (1–4). Loss of response after discontinuation of therapy was rapid, with a median progression-free survival of 4 months (95% CI: 2–6). Median overall survival (OS) from the time of therapy discontinuation was 15 months (95% CI: 6–24). Patients who received 12 cycles of therapy or more had significantly better OS (median: 20 months [95% CI: 12–27]) than those who received fewer than 12 cycles (median: 4 months [95% CI: 1–8]) (p = 0.043). Poor-risk cytogenetics were also associated with lower 1-year OS (33% versus 69%; p = 0.046). According to these results and considering the poor prognosis after HMA failure, HMA interruption should be avoided once a sustained response has been achieved.