Hematologic and cytogenetic (CTG) response to lenalidomide (CC-5031) in patients with transfusion-dependent (TD) myelodysplastic syndrome (MDS) and chromosome 5q31 deletion: Results of the multicenter MDS-003 Study.
Reviewer: Christopher Dolinsky, MD
University of Pennsylvania School of Medicine
Last Modified: May 16, 2005
Presenter: A.F. List
Presenter's Affiliation: Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
Type of Session: Plenary
- The most common cytogenetic abnormality in patients with transfusion dependent myelodysplastic syndrome (MDS) is deletion of chromosome 5q31.
- This disease has an indolent course, and is often refractory to therapy.
- A novel medication, lenalidomide, has shown promsing results in the laboratory.
- Lenalidomide may potentiate cellular signals for erythropoesis.
- A small phase I/II trial using lenalidomide demonstrated sustained transfusion independence and cytogenetic regression in multiple patients with 5q31del MDS unresponsive to cytokine therapy.
Materials and Methods
- A multicenter phase II trial of lenalidomide enrolled 148 patients with low or intermediate risk 5q31del MDS who were transfusion dependent.
- Transfusion dependence was defined as requiring >= 2U PRBC every 8 weeks.
- Patients had to have ANC >= 500, and platelets >=50,000.
- Lenalidomide was given as either 10mg/day for 3 weeks, followed by a one week break or as 10mg/day every day with dose reduced as necessary.
- Response was assessed at 24 weeks using a blinded pathology review and cytogenetic analysis.
- 111/148 patients had isolated 5q31del, and 37/148 had 5q31del plus at least one other cytogenetic abnormality.
- Median duration of MDS diagnosis was 3.4 years.
- Median age was 71 years, and 66% of patients were female.
- Median transfusion dependence was 5U PRBC every 8 weeks.
- Transfusion independence was defined as >= 56 days without requiring a transfusion.
- Transfusion independence was seen in 64% of patients.
- Median response was an increase in hemoglobin of 3.9/dl, and median time to response was 4 weeks.
- Of the patients who became transfusion independent, 75% of them had a complete cytogenetic response.
- Pathologic complete response was documented in 29% of patients evaluable.
- The median duration of response has not been reached, and is thus longer than 47 weeks.
- The most common grade III adverse events were neutropenia (55%) and thrombocytopenia (54%).
- 15 deaths occurred on study, and 2 deaths were considered treatment related.
- Lenalidomide is highly active in lower risk, transfusion dependent patients with 5q31del MDS.
- The response to lenalidomide is rapid, durable, and associated with a high rate of cytogenetic response.
- The medication causes a high rate of neutropenia and thrombocytopenia.
- Lenalidomide is extremely promising, and further research with it is warranted.