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.

Author's Conclusions

  • 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.

Clinical/Scientific Implications

The authors presented an exciting new development for the treatment of a specific subset of patients with MDS.  This compound is far more active than any current therapy on the market.  In the future, it will be interesting to see how the use of lenalidomide affects other outcomes, including overall survival, disease free survival, and quality of life.  Because this is an indolent disease, this study examined patients with a 3.4 year median length of diagnosis.  It may be appropriate to consider research using this compound sooner after a diagnosis of MDS is made.  Five to ten percent of AML patients also have a 5q deletion, and they tend to respond poorly to standard chemotherapy.  This compound will almost certainly be studied in this subgroup of patients.  This is an important abstract that will change the way patients with MDS are managed.