Initial Low Dose Lenalidomide Over 2 Years Improves Treatment Response Among Non-Transfusion-Dependent Patients With Low-Risk MDS

SintraREV Phase 3 Study Results

According to results from a phase 3 trial, an initial treatment of low doses of lenalidomide distributed across 2 years was shown to safely prolong the time to transfusion-dependency and improve responses among non-transfusion-dependent patients with low-risk, deletion(5q) myelodysplastic syndrome (MDS).

The randomized, double-blind SintraREV trial was conducted at 22 university hospitals in Spain, France, and Germany. Eligible patients included 61 patients who were 18 years or older diagnosed with low-risk or intermediate-1-risk del(5q) MDS non-transfusion-dependent anemia per International Prostate Symptom Score (IPSS) guidelines, were erythropoietin-stimulating agents naive, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less.

Patients were randomly assigned on a 2-to-1 basis to receive lenalidomide 5 mg daily in 28-day cycles versus placebo for 2 years. The study’s primary end point was time to transfusion dependency based on a blinded independent central review, and overall analysis were by intent-to-treat (ITT) and evaluable population. Safety analyses included all patients who received at least 1 dose of treatment. Between February 15, 2010, and Feb 21, 2018, all eligible 61 patients were randomly assigned to receive lenalidomide (n=40; 2 patients did not receive treatment) or placebo (n=21). The median follow-up time was 60.6 (interquartile range [IQR] 32.1 to 73.9) months.

Trial results demonstrated that the primary end point, the median time to transfusion dependency, was not reached (95% confidence interval [CI], not applicable) in the lenalidomide cohort versus 11.6 months (95% CI, 0 to 30.1) in the placebo group (P =0.0027). Additionally, lenalidomide significantly reduced the risk of transfusion dependency by 69.8% (hazard ratio [HR] 0.302, 95% CI, 0.132 to 0.692; P = 0.0046).

When measuring the safety profile, the most frequent treatment-related adverse event was neutropenia, which occurred in 24 (63%) of 38 patients in the lenalidomide group (grade 3 and 4 in 17 [45%] patients and 1 [3%], respectively) and in 4 (19%) of 21 patients in the placebo group (grade 3 in 1 [5%] patient). Furthermore, thrombocytopenia was observed in 7 (18%) of 38 patients receiving lenalidomide (grade 3 in 2 [5%] patients).

Regarding non-hematological toxicities, skin disorders (rash, 9 [23%] of 38 patients) were the most frequently described among patients receiving lenalidomide, being grade 3 in 1 (3%) of 38 patients. Researchers noted that 19 serious adverse events were reported in 13 patients; 18 in the lenalidomide group and 1 in the placebo group, 5 of which were potentially related to the study drug. No treatment-related deaths were seen in this trial.

"An early approach with low doses of lenalidomide across 2 years delays the time to transfusion dependency and improves the rate and quality of the responses, with a manageable safety profile in patients who are non-transfusion dependent with del(5q) low-risk myelodysplastic syndromes,” concluded lead study author María Díez-Campelo, PhD, Hospital Universitario de Salamanca, Salamanca, Spain, and colleagues.

Source:

Díez-Campelo M, López-Cadenas F, Xicoy B, et al. Low dose lenalidomide versus placebo in non-transfusion dependent patients with low risk, del(5q) myelodysplastic syndromes (SintraREV): A randomized, double-blind, phase 3 trial.