The spokesperson further clarified that the FDA update discussed in the Beacon article above was intended, in part, to explain the agency’s rationale for the changes to Revlimid’s prescribing information published on the FDA website in March.

Key Text of FDA Drug Safety Communication:
Safety review update of cancer drug Revlimid (lenalidomide) and risk of developing new types of malignancies

Safety Announcement

The U.S. Food and Drug Administration (FDA) is informing the public of an increased risk of second primary malig­nancies (new types of cancer) in patients with newly-diagnosed multiple myeloma who received Revlimid (lenalidomide). Clinical trials conducted after Revlimid was approved showed that newly-diagnosed patients treated with Revlimid had an increased risk of developing second primary malignancies compared to similar patients who received a placebo. Specifically, these trials showed there was an increased risk of developing acute myelogenous leukemia, myelodysplastic syndromes, and Hodgkin lymphoma.

This safety information has been added to the Warnings and Precautions section of the Revlimid drug label. The patient Medication Guide is also being updated to inform patients about this risk.

Healthcare professionals should consider both the potential benefit of Revlimid and the risk of second primary malignancies when deciding to treat patients with this drug, and monitor patients for this risk.

Patients should contact their healthcare professional if they have any questions or concerns about Revlimid …

Data Summary

FDA reviewed controlled clinical trials of Revlimid as maintenance therapy in patients with newly-diagnosed multiple myeloma and for the treatment of relapsed/refractory multiple myeloma, to evaluate the risk of developing a second primary malignancy with Revlimid.

Second primary malignancies in patients with newly diagnosed multiple myeloma

In three prospective, randomized trials, patients with newly-diagnosed multiple myeloma received initial chemotherapy or chemotherapy plus blood stem cell transplantation followed by treatment with Revlimid or a placebo. This treatment protocol was used to study the effect of Revlimid as maintenance therapy. A pooled analysis of the three ongoing trials, as of February 28, 2011, showed 65 second primary malig­nancies among 824 patients in the Revlimid treatment arms compared to 19 second primary malig­nancies among 665 patients in the treatment arms that did not include Revlimid maintenance (7.9% vs. 2.8%; p<0.001). This difference is almost a three-fold increase in new malignancies for the groups receiving Revlimid versus the groups that did not receive Revlimid. The second primary malignancies noted included acute myelogenous leukemia (AML), myelodysplastic syndromes (MDS), and B-cell malignancies. Overall, 30 (3.6%) second primary hematologic malignancies were reported in the Revlimid treatment arms (22 MDS/AML, 5 Hodgkin lymphoma, 3 B-cell acute lymphoblastic leukemia) compared with 2 (0.3%) cases of AML in the study arms not receiving Revlimid. The median time from start of Revlimid to a diagnosis of a second primary malignancy was two years. Based on the available data, there appears to be no difference in the incidence of non-melanoma skin cancers or of solid tumors between the patients who received Revlimid and those who did not.

Second primary malignancies in patients with relapsed/refractory multiple myeloma

A retrospective pooled analysis of second primary malignancies also was conducted on data derived from the two clinical trials that supported the initial FDA approval for relapsed multiple myeloma. These were multicenter, double-blind, placebo-controlled, parallel-group trials of Revlimid plus high-dose dexa­methasone therapy versus dexa­methasone alone in the treatment of patients with relapsed or refractory multiple myeloma. The incidence rates of developing a second primary malignancy during the treatment phase of these trials were 3.98 and 1.38 per 100 person-years for patients in the Revlimid / dexa­metha­sone and the placebo / dexamethasone groups, respectively. The higher incidence rate of second primary malignancies in the Revlimid / dexa­metha­sone group was largely accounted for by the higher incidence of non-melanoma skin cancers with Revlimid (2.4 vs. 0.91 per 100 person-years for the Revlimid / dexa­metha­sone and placebo / dexamethasone groups, respectively). The patients in the Revlimid / dexa­metha­sone group had longer on-study treatment time compared to the placebo / dexamethasone group (467 person-years vs. 218.7 person-years, respectively). When adjusted for the differences in observation time on-study, the incidence rate of invasive non-melanoma skin cancers was not substantially different between the two groups (1.71 vs. 0.91 per 100 person-years, respectively).