Hypomethylating agents alone show poor long-term OS for high-risk myelodysplastic syndrome

Hypomethylating agents azacitidine and decitabine appeared associated with a 5-year OS probability rate of 4% among patients with myelodysplastic syndrome with refractory anemia with excess blasts who did not undergo allogeneic stem cell transplantation, according to a study published in Blood.

“The approval of hypomethylating agents azacitidine [Vidaza, Celgene] and decitabine for therapy of myelodysplastic syndromes has been celebrated by the [myelodysplastic syndrome] community as a major milestone in improving the clinical outcomes of patients,” Amer M. Zeidan, MBBS, MHS, assistant professor of medicine at Yale University and the COPPER Center, and colleagues wrote. “While both drugs lead to hematologic responses and improvement in quality of life, only azacitidine prolonged OS among patients with international prognostic scoring system [IPSS] intermediate-2 and high-risk categories (ie, higher-risk [myelodysplastic syndrome]) compared to conventional care regimens in a randomized trial (AZA-001).”

Further, published trials have limited duration of follow-up, making 5-year OS rates unreliable.

Zeidan and colleagues studied 1,187 patients (median age, 77 years; 63.8% men) from the SEER-Medicare linked database with myelodysplastic syndrome. Of the patients, 336 had refractory anemia with excess blasts, a histology that often overlaps with higher-risk myelodysplastic syndrome per IPSS criteria.

Patients initiated hypomethylating therapy for at least 10 days between 2004 and 2009. Researchers excluded patients who received allogeneic stem cell transplantation.

Follow-up continued until death or December 2013, whichever came first, allowing at least 4 years of follow-up for all patients.

Seventy-nine percent of patients received azacitidine and 21% received decitabine. A majority (72.6%) of patients received at least four cycles of therapy and about half (49.5%) received at least six cycles, with no differences between azacitidine and decitabine.

Results — also presented at the ASH Annual Meeting and Exposition in December — showed a median OS for the entire cohort of 14 months (95% CI, 13-15); OS probability at 5 years was 8% (95% CI, 7-10).

Among patients with refractory anemia with excess blasts, 96.7% had died by the end of the study. Median OS for this subgroup was 11 months (95% CI, 10-12) and 5-year OS probability was 4% (95% CI, 2-6). No significant difference appeared between those treated with azacitidine compared with decitabine.

Patients who received at least six hypomethylating agent cycles had significantly higher 5-year OS (6%; 95% CI, 3-11) than those who received fewer than six cycles (1%; 95% CI, 0-3).

Choice of hypomethylating therapy was not associated with increased probably of long-term survival among patients with refractory anemia with excess blasts (decitabine vs. azacitidine, HR = 0.96; 95% CI, 0.7-1.31).

“These results offer a realistic estimate of the long-term survival probability for patients older than 65 years who wish to be treated definitively with [hypomethylating agents] instead of [allogeneic stem cell transplantation],” the researchers wrote. “Further research should attempt to identify biologic and/or clinical markers that could predict prolonged survival with [hypomethylating agent] therapy.

“Furthermore, our findings add to the accumulating body of evidence regarding the suboptimal performance of [hypomethylating agents] for treatment of [myelodysplastic syndrome] in the real-life setting and provide rationale for strong consideration of alternative management strategies including allogeneic stem cell transplantation] or clinical trials for all patients with higher risk [myelodysplastic syndrome],” the researchers added. – by Cassie Homer

Disclosures: Zeidan reports consultant roles with Ariad, Celgene, Gilead, Incyte and Pfizer and speaker fees for Ariad. Please see the full study for all other authors’ relevant financial disclosures.