The MDS Beacon™

A retrospective analysis indicates that treatment with Revlimid improved survival in lower-risk myelodysplastic syndromes patients with a deletion in chromo­some 5 who initially were transfusion dependent.

Dr. Andrea Kuendgen of the Heinrich-Heine-Universitaet in Duesseldorf, Germany, presented the findings at the 2011 American Society of Hema­tology (ASH) conference in San Diego last week.

Revlimid (lenalidomide) is approved by the U.S. Food and Drug Admin­istration as a treatment for the subgroup of lower-risk myelodys­plastic syndromes (MDS) patients who are dependent on blood transfusions and have a deletion of the long arm in chromosome 5 (“del5q”).

The drug, which is a close chemical cousin of thalidomide, was approved by the FDA based on data showing that patients treated with it are able to become transfusion independent.

Two large multi-center clinical trials, MDS-003 and MDS-004, have looked at the impact of Revlimid treatment on MDS patients.

All patients in the MDS-003 trial received Revlimid, whereas patients in the MDS-004 trial were randomized to receive Revlimid or a placebo.  However, patients in the placebo arm of the MDS-004 trial were allowed to crossover to the Revlimid arm early on in the study.

As a result, researchers were unable to assess the impact of Revlimid on overall survival and progression to leukemia.

In the present study, researchers retrospectively compared data from 295 patients from the MDS-003 and MDS-004 trials with those of 125 untreated MDS patients with del5q from a large patient registry. Patients in the control group also had lower-risk MDS and were transfusion-dependent.

At two years, 7 percent of the Revlimid-treated patients progressed to leukemia, compared to 12 percent of the untreated, control-group patients.

At five years, 23 percent of the Revlimid-treated patients and 20 percent of the untreated patients progressed to leukemia.

These differences in time to progression to leukemia were not, however, statistically significant.

In regard to survival, the overall survival rate was higher for the Revlimid-treated group than the untreated group at two years (90 percent versus 74 percent) and at five years (54 percent versus 41 percent).

Also, patients who were treated with Revlimid lived longer than patients who did not receive treatment (a median of 5.2 years versus a median of 3.8 years).

Once again, however, the differences between the two patient groups were not statistically significant.

The authors therefore used statistical modeling techniques to determine more clearly which factors affect an MDS patient’s risk of progressing to leukemia and a patient’s risk of death.

This modeling showed that treatment with Revlimid leads to a reduced risk of death that is both clinically and statistically significant.

The modeling also showed that Revlimid does not increase the risk of MDS patients progressing to leukemia.  This result is important in part because there have been concerns that patients treated with Revlimid might be at an increased risk of developing so-called “secondary” cancers (see related Beacon news).

The modeling likewise confirmed the importance of several factors that have been shown in earlier research to increase the risk of an MDS patient progressing to leukemia.  These factors include having more than one additional chromosomal abnormality besides del5q, 5 percent to 10 percent of immature blood cells (blasts), and higher transfusion needs.

For more information, please see abstract 119 at the ASH 2011 meeting website.