Treatment of multiple myeloma with lenalidomide (Revlimid) as maintenance therapy is associated with an increased risk of second primary cancers, the FDA warned.
In three trials involving newly diagnosed patients initially treated with chemotherapy and stem cell transplantation, followed by maintenance lenalidomide or a placebo, the risk of a second primary cancer was increased about threefold, the agency said.
Trials involving relapsed/refractory patients – on which the drug's initial approval was based – did not show a significant increase in risk after adjustment for the length of time patients took the drug, the agency said.
A pooled analysis of the three maintenance trials showed that, as of Feb. 28, 2011, there had been 65 second primary malignancies among 824 lenalidomide patients and 19 among 665 patients in the treatment arms that did not include the drug.
The difference in incidence -- 7.9% versus 2.8% -- was significant at P<0.001.
The second primary cancers included acute myelogenous leukemia, myelodysplastic syndromes, and B-cell malignancies, the FDA reported, and, overall, 30 second primary hematologic malignancies were associated with lenalidomide, compared with two among patients not getting the drug.
There appears to be no difference in the incidence of nonmelanoma skin cancers or of solid tumors, the agency said.
The agency said the drug's label and patient medication guide will be amended to reflect the increased risk.
Patients and physicians should balance the benefit of the drug with the increased risk of second primary cancers, the agency suggested, and doctors should monitor patients on lenalidomide closely.