Lenalidomide for treating myelodysplastic syndromes (MDS) associated with an isolated deletion 5q cytogenetic abnormality.
Issued: September 2014
Lenalidomide is recommended as an option for treating transfusion-dependent anaemia caused by IPSS low or intermediate-1 risk MDS associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate.
The drug cost of lenalidomide (excluding any related costs) for people who remain on treatment for more than 26 cycles (each of 28 days) will be met by the company.
Evidence for clinical effectiveness was gained from a single phase III, randomised, double-blind multinational study (MDS-004), which compared lenalidomide 10 mg (n=69) and lenalidomide 5 mg (n=69) with placebo (n=67) in patients with low/int-1 MDS associated with a deletion 5q cytogenetic abnormality. Crossover was permitted at 16 weeks in those achieving an inadequate response.
Rates of transfusion independence at 26 weeks were significantly higher in the lenalidomide arm (lenalidomide 10 mg: 56.1%; placebo: 5.9%; p<0.001). Quality of life, measured by Functional Assessment of Cancer Therapy-Anaemia (FACT-An) questionnaire was also significantly improved (mean change, lenalidomide 10 mg: 5.8, placebo: -2.5; p<0.05). There was no significant difference in time to progression to AML (lenalidomide 10 mg 36.1 months: placebo, 30.9 months) or in overall survival (lenalidomide 10 mg: 36.9 months, placebo: 35.9 months). However, it was recognised that the ability to cross over to lenalidomide in the placebo arm in the MDS-004 study could result in any survival benefits with lenalidomide being underestimated. Certainly, separate mortality curves for people who were transfusion dependent or independent at 8 weeks in MDS-004 indicate that survival was strongly related to transfusion status.
Adverse event rates were more common in the lenalidomide group (lenalidomide 10 mg 95.7%: placebo 49.3%): most frequently neutropenia (75.4% in the lenalidomide groups) and thrombocytopenia (47.8% in the lenalidomide 10 mg group). Grade 3 or 4 pneumonia was reported in 4.3% in the lenalidomide 10 mg group, 1.4% in the lenalidomide 5 mg group and 1.5% in the placebo group.
The Committee concluded that lenalidomide is a clinically effective treatment for people with low- or intermediate-1-risk MDS associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate, because it was associated with a statistically significant improvement in transfusion independence and health related quality of life compared with placebo. The Committee agreed that it was plausible for lenalidomide to indirectly improve overall survival by improving transfusion independence.
The Committee concluded that, although lenalidomide is associated with some adverse reactions, these can be managed by dose interruptions.
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