Lenalidomide feasible for lower-risk MDS
MedWire News: Lenalidomide effectively induces red blood cell transfusion independence (RBC-TI) in patients with lower-risk myelodysplastic syndromes (MDS) with a 5q deletion (del5q), phase III study data show.
International Prognostic Scoring System (IPSS) low- or intermediate-1-risk del5q MDS is characterized by macrocytic anemia and short response duration when treated with erythropoiesis-stimulating agents, explain Pierre Fenaux (Université Paris XIII, Bobigny, France) and colleagues.
"Lenalidomide is an immunomodulatory agent with multiple mechanisms of action, which are thought to include the direct targeting of MDS clones, immunomodulation, erythropoiesis restoration, and angiogenesis inhibition," they add.
A previous single-arm phase II study (MDS-003) showed that two-thirds of patients with low- or intermediate-1- risk MDS with del5q31 achieved RBC-TI for at least 8 weeks, while three-quarters experienced cytogenic improvement when treated with lenalidomide 10 mg.
Based on these findings, Fenaux and team conducted a phase III randomized, double-blind study to assess the efficacy and safety of lenalidomide in 205 red blood cell (RBC) transfusion-dependent patients with IPSS low- or intermediate-1-risk del5q31 myelodysplastic syndromes.
Patients received lenalidomide 10 mg/day on days 1-21 (n=69) or 5 mg/day on days 1-28 (n=69) of 28-day cycles, or placebo (n=67). Crossover to lenalidomide or higher dose was allowed after 16 weeks.
The researchers report that significantly more patients in the lenalidomide 10- and 5-mg groups achieved the primary study endpoint of RBC-TI for at least 26 weeks than those in the placebo group, at 56.1% and 42.6% versus 5.9%, respectively.
Furthermore, RBC-TI was achieved rapidly, with the onset of response occurring during cycles 1 and 2 for 48.8% and 37.2% of all lenalidomide-treated patients, respectively.
Responses also appeared to be long-lasting since the median response duration was not reached after 1.6 years of follow-up, and 60% to 67% of patients had an ongoing response without progression to acute myeloid leukemia (AML) at this time point.
The team observed a trend for a higher cytogenic response rate in the 10-mg group compared with the 5-mg group, at 50% versus 25%, but the difference was not statistically significant.
The secondary endpoints of 3-year overall survival and risk for progression to AML were 56.5% and 25.1%, respectively.
Multivariate analysis showed that achievement of RBC-TI for at least 8 weeks in patients randomized to lenalidomide was associated with significant 47% and 42% reductions in the relative risks for death and AML progression or death, respectively.
Of note, clinically meaningful quality of life improvements (measured with the Functional Assess of Cancer Therapy-Anemia questionnaire) were apparent in lenalidomide-treated patients at week 12 and lasted through week 48 in patients with RBC-TI for at least 26 weeks.
The incidence of adverse events, most commonly neutropenia and thrombocytopenia, was similar for both lenalidomide doses, and generally occurred within the first two cycles and decreased thereafter. There were no treatment-related deaths because of neutropenic infection.
Fenaux and co-authors conclude in the journal Blood that although continued follow-up is needed, "these findings support the use of a starting dose of 10mg, with subsequent dose reductions or interruptions if needed."
By Laura Dean