Second-line therapies do not improve OS in non-deleted 5q lower-risk myelodysplastic syndromes

No commonly used second-line treatments for patients with non-deleted 5q lower-risk myelodysplastic syndromes improved patients’ survival, a retrospective cohort study in France found.

“Erythropoiesis-stimulating agents are often the first line of treatment for anemia in patients with lower-risk myelodysplastic syndromes who lack the 5q deletion,” Sophie Park, MD, PhD, of the Clinique Universitaire d’Hematologie, Centre Hospitalier Universitaire Grenoble Alpes, France, and colleagues wrote. “Response rates range from 30% to 60%, with a median duration of response of 20 to 24 months. Recently, the hypomethylating agents azacytidine and decitabine and the immunomodulating agent lenalidomide demonstrated efficacy in treating anemia in patients with lower-risk myelodysplastic syndromes without 5q deletion and erythropoiesis-stimulating agent resistance, with [red blood cell] transfusion independence rates of 20% to 40%. No studies have compared the effect of these drugs on disease progression and OS versus best supportive care.”

Park and colleagues used multiple databases in Europe and the United States to review 1,698 patients with non-deleted 5q lower-risk myelodysplastic syndromes who received erythropoiesis-stimulating agents.

Overall, 61.5% of patients showed an erythroid response to erythropoiesis-stimulating agents. The median duration of response was 17 months. A total of 1,147 patients experienced erythropoiesis-stimulating agent failure, of whom 653 experienced primary failure and 494 relapsed after initially responding. Failure conferred a higher risk for progression to acute myeloid leukemia, a development that did not produce any difference in OS.

Thirty-nine percent of patients (n = 450) received second-line treatment, including hypomethylating agents (n = 194), lenalidomide (n = 148) and other treatments (n = 108). Another 697 patients received only red blood cell transfusions.

Patients who received hypomethylating agents and those who received lenalidomide had a 5-year AML incidence of 20.3%; those who received other treatments demonstrated an 11.3% AML incidence.

Patients who received hypomethylating agents achieved a 5-year OS of 36.5%, compared with 41.7% in those treated with lenalidomide and 51% for other treatments (P = .21). Multivariable analysis — adjusted for age, sex, revised International Prognostic Scoring System score and progression at ESA failure — showed similar OS across all groups.

“Second-line treatments with lenalidomide or hypomethylating agents after erythropoiesis-stimulating agent failure did not significantly influence OS,” the researchers wrote. “This study may be important in designing future clinical trials involving patients with lower-risk myelodysplastic syndromes for whom erythropoiesis-stimulating agent treatment fails, in whom novel treatments are required. Parameters predicting worse outcome, including IPSS-R subtype and duration of response to erythropoiesis-stimulating agents, could indicate a more intensive therapeutic approach, including allogeneic stem-cell transplantation.” – by Andy Polhamus

Disclosure: Park reports a consulting or advisory role with Novartis, as well as research funding from Celgene and Novartis. Please see the full study for a list of all other researchers’ relevant financial disclosures.