The Food and Drug Administration has added a warning about second-cancer risk to the label of lenalidomide, a widely used multiple myeloma drug, after a safety review lasting about 1 year.
Treatment with lenalidomide (Revlimid) for newly diagnosed multiple myeloma is associated with almost a threefold increased risk of developing secondary primary malignancies, the agency announced on May 7. The finding was based on three postapproval trials of lenalidomide as maintenance therapy in newly diagnosed patients.
"Specifically, these trials showed there was an increased risk of developing acute myelogenous leukemia, myelodysplastic syndromes, and Hodgkin lymphoma," the FDA said. No increase was seen in incidence of nonmelanoma skin cancers and solid tumors.
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It noted that as of Feb. 28, 2011, a pooled analysis showed there were 65 second primary malignancies among 824 patients treated with lenalidomide vs. 19 second primary malignancies among 665 patients in treatment arms that did not include lenalidomide maintenance (7.9% vs. 2.8%, respectively; P less than .001). "The median time from start of Revlimid to a diagnosis of a second primary malignancy was two years," the agency said.
The three studies were designed to evaluate the effect of lenalidomide as maintenance therapy, compared with placebo, after patients with newly diagnosed multiple myeloma had received initial chemotherapy or chemotherapy plus a hematopoietic stem cell transplant. A thalidomide analogue, lenalidomide is approved in combination with dexamethasone to treat patients with multiple myeloma who have been treated previously.
The FDA also analyzed data from two clinical trials that were the basis of the approval in these patients – and it also found a higher incidence of second primary malignancies with lenalidomide plus dexamethasone, compared with dexamethasone alone. A higher incidence of nonmelanoma skin cancers accounted for most of this difference, however, and the agency said this was no longer significant after adjusting for the time on treatment.
The FDA recommends that clinicians monitor patients treated with lenalidomide for the development of secondary primary malignancies, and "take into account both the potential benefit of Revlimid and the risk of second primary malignancies when considering treatment with Revlimid."
The new safety information is being added to the warnings and precautions section of the label, and to the patient Medication Guide. Clinicians encourage patients treated with lenalidomide to read the Medication Guide, a handout that is distributed with each filled prescription, including refills, the FDA said, and patients should consult their health care professionals if they have any questions or concerns.
The FDA statement is available at http://www.fda.gov/Drugs/DrugSafety/ucm302939.htm. Adverse events associated with lenalidomide should be reported to the FDA’s MedWatch program at www.fda.gov/medwatch/ or 800-332-1088.