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Lenalidomide prolongs transfusion independence in some patients with myelodysplastic syndrome
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Lenalidomide induced sustained red blood cell transfusion independence in patients with transfusion-dependent lower-risk myelodysplastic syndrome who were refractory to or ineligible for erythropoiesis-stimulating agents, according to the results of an international phase 3 randomized controlled trial.
A significant number of patients who responded to lenalidomide (Revlimid, Celgene) remained transfusion independent for 24 weeks or more, results showed.
Anemia represents the main therapeutic challenge of patients with lower-risk myelodysplastic syndrome, and these patients require repeated red blood cell transfusions. Erythropoiesis-stimulating agents are the first-line option for patients without deletion 5q (non-del[5q]); however, most patients lose their response to this therapy over time.
Valeria Santini, MD, associate professor of hematology at University of Florence Medical School in Italy, and colleagues evaluated the safety and efficacy of lenalidomide in 239 patients (median age, 71 years; range, 43-87) with lower-risk, transfusion-dependent non-del(5q) myelodysplastic syndrome. All patients were refractory to or ineligible for erythropoiesis-stimulating agents.
The researchers randomly assigned patients 10 mg of daily lenalidomide (n = 160) or placebo (n = 79) for a 28-day cycle.
Red blood cell transfusion independence for 8 or more weeks served as the primary endpoint. Secondary endpoints included transfusion independence for 24 weeks or more, duration of transfusion independence, erythroid response, health-related quality of life and safety.
A significantly greater proportion of patients assigned lenalidomide achieved the study’s primary endpoint (26.9% vs. 2.5%; P < .001). No patients assigned placebo achieved transfusion independence for 24 weeks or more, compared with 17.5% of patients assigned lenalidomide (P < .001).
Patients who achieved the primary endpoint with lenalidomide were on treatment for a median of 30.9 weeks (95% CI, 20.7-59.1), and median time to onset of response was 10.1 weeks (range, 0.3-23.6). Six patients had ongoing responses (mean duration, 553 days; range, 301-866) and remained on treatment at the time of reporting.
A greater proportion of patients in the lenalidomide arm achieved a transfusion reduction of four or more packed red blood cell units at 112 days (21.8 % vs. 0%).
Patients with lower baseline endogenous erythropoietin had higher response rates to lenalidomide (≤ 500 mU/mL vs. > 500 mU/mL, 34% vs. 15.5%; P = .015).
Both groups exhibited similar rates of health-related quality of life at 12 weeks. A post-hoc analysis showed that achievement of transfusion independence for 8 or more weeks appeared associated with improvements to all quality-of-life domains (P < .01).
More patients assigned lenalidomide experienced grade 3 or grade 4 neutropenia (61.9% vs. 12.7%) and thrombocytopenia (35.6% vs. 3.8%). Five patients assigned lenalidomide experienced venous thrombosis; no patients had pulmonary embolism.
Fifty-one patients assigned lenalidomide and nine patients assigned placebo discontinued treatment due to adverse events.
Median OS has not been reached; the researchers are continuing to collect OS data.
“Overall, these data support the possible clinical benefits of lenalidomide in lower-risk non-del(5q) myelodysplastic syndrome,” Santini and colleagues wrote. “The subgroup of patients with myelodysplastic syndrome who responded to lenalidomide needs further characterization, and molecular studies are going.”
Mikkael Sekeres
The study findings are accompanied by limitations that should be considered before lenalidomide treatment becomes part of standard practice for these patients, Mikkael Sekeres, MD, MS, director of the leukemia program and vice-chair for clinical research at Cleveland Clinic Taussig Cancer Institute, wrote in a related editorial.
“For the majority of these patients, quality of life did not improve, and neither did transfusion requirements, and lenalidomide use in patients with non-del(5q) myelodysplastic syndrome will continue to be relegated to the off-label realm,” Sekeres wrote. “For a tantalizing few, including at least one patient whose response lasted for 5 years, the drug is extremely effective, and it is now our responsibility, as clinical and translational scientists, to determine how we can better identify those people, and make the long day’s journey into night even longer.” – by Cameron Kelsall
Disclosure: Santini reports honoraria from and consultant roles with Celgene, Janssen and Novartis. Sekeres reports honoraria from and a consultant role with Celgene. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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