The MDS Beacon™

European researchers report that myelodysplastic syndromes (MDS) patients with deletion-5q syndrome (del-5q) have an increased risk of progressing to acute myeloid leukemia (AML) if they do not show blood cell and chromosome improvements after treatment with Revlimid (lenalidomide).  Their findings were published in the journal Annals of Hematology in October.

Revlimid has been used to treat Low- or Intermediate-1 risk MDS subtypes, especially those who require red blood cell transfusions or have del-5q.  The del-5q mutation is a chromosomal abnormality which is characterized by a missing ‘q’ arm of chromosome 5.  Many del-5q MDS patients experience temporarily lowered white blood cell (neutropenia) and platelet (thrombocytopenia) counts. 

Clinical trials have shown that patients taking Revlimid consistently become independent of blood transfusions and show a complete cytogenetic, or chromosomal, response.  A complete cytogenetic response is defined by no abnormal cells present in a specific stage of cell division. 

Although the exact mechanism of Revlimid has yet to be fully characterized, it relieves symptoms of MDS by stimulating the immune system, causing cell death, and inhibiting new blood vessel growth.

The researchers performed a long-term follow-up analysis of 42 Low or Intermediate-1 risk patients with del-5q receiving Revlimid therapy.  Patients received either 10 mg daily or 10 mg for 21 in 28 days.  They were treated until the disease progressed or they relapsed.  

At a median follow-up of 40 months, 58 percent of patients had improved red blood cell production and 48 percent showed a full or partial chromosomal response. 

Thirty-six percent of patients had progressed to AML, and 87 percent of these patients had developed other chromosomal abnormalities in addition to del-5q. 

Results showed del-5q patients who responded to Revlimid treatment with a cytogenetic response had fewer incidents of AML progression.  Three and five years after study entry, 10 and 21 percent of patients who showed a cytogenetic response to Revlimid had progressed to AML, respectively.  In contrast, 46 and 60 percent of patients without cytogenetic response had progressed to AML at three and five year follow-up, respectively.

The study authors conclude that cytogenetic response after Revlimid treatment may be an indicator for a decreased risk of AML progression.  Patients without a cytogenetic response to Revlimid are more likely to progress to AML than those who do show a cytogenetic response.

However, the authors feel their research cannot answer the question of whether or not Revlimid increases the risk of AML transformation.

Dr. Brigitte Schlegelberger, one of the study authors, said in an email to the MDS Beacon “A definite answer cannot be given, since it cannot be excluded that a subpopulation containing genetic lesions that trigger the transformation was present before treatment.” She added, however,”a leukemic transformation rate of more than 60 percent seems quite high.”

The authors suggest regularly monitoring del-5q patients taking Revlimid in order to identity patients who may be at an increased risk for AML progression..

For more information, please see the Annals of Hematology (abstract).