Note: This abstract was presented at the 2012 ASCO annual meeting in June 2012. The full abstract may be reviewed on the ASCO Annual Meeting Web site. Use the abstract number to access the full report.
Abstract # 6522
The FDA approved lenalidomide in 2005 for treatment of lower risk MDS patients (low or intermediate-1 risk IPSS score) with deletion 5q abnormalities who are dependent on red blood cell (RBC) transfusions. This approval was based on the results of the MDS-003 study, which showed that a majority of such patients who were treated with lenalidomide achieved sustained independence from RBC transfusions. Moreover, most patients saw either resolution or improvement of their del(5q) cytogenetic abnormality (ie. a complete or partial cytogenetic response). The benefit of lenalidomide in del(5q) MDS was recently confirmed in MDS-004, a randomized, placebo-controlled trial, which again demonstrated that lenalidomide treatment affords many patients a sustained RBC transfusion independence and a significant cytogenetic response.
Taking the MDS-003 and MDS-004 trials together, the most common serious side effects of lenalidomide therapy are neutropenia (low neutrophil count) and thrombocytopenia (low platelet count). These low blood counts can lead to infectious or bleeding complications, safety concerns that are thought to be particularly important in elderly patients. In this study, Fenaux and colleagues re-examined the combined data from MDS-003 and MDS-004, focusing specifically on the effectiveness and safety of lenalidomide in patients 75 years of age and older compared to those under 75 years of age.
The effectiveness of lenalidomide was comparable between older and younger patients, as reflected by equivalent rates of RBC transfusion-independence, cytogenetic response, and AML progression. While patientsover 75 years old had a shorter duration of lenalidomide therapy, there were no differences in the reasons for discontinuation of treatment. From a safety perspective, lenalidomide caused a similar range of side effects in older and younger patients. While patients over75 years old were nearly twice as likely to require dose-reduction due to thrombocytopenia (30% vs. 17%), very few needed to stop treatment altogether for this reason (4% vs. 3%). Neutropenia, in and of itself, did not appear to affect older patients selectively, although infections were somewhat more common in those over75 years old (36% vs. 20%).
In summary, lenalidomide appears to be safe and effective in elderly patients with lower risk, transfusion-dependent MDS with deletion 5q abnormalities. On these clinical trials, patients over75 years old were generally treated for a shorter duration and were more likely to require dose-reductions related to low platelet counts. An increased rate of infections is the most notable safety concern in this older population and bears close monitoring. Further studies will help clarify the significance of these results.