6074 Background: Half of cancer therapies are used off-label, but regulations prohibit package inserts from describing toxicities that occur only in these settings. In 2003, RADAR reported VTE rates of 20% to 62% when thalidomide, approved for leprosy treatment, was used off-label (with dexamethasone) for multiple myeloma. In 2005, the Connecticut attorney general requested that a black box warn of high rates of VTE when thalidomide is used off-label. Subsequently, the thalidomide analogue, lenalidomide, received FDA approval as a myelodysplasia therapy. In phase II/III trials, multiple myeloma response rates were 60% to 92% with lenalidomide/dex therapy. Methods: Published literature, abstracts, and package inserts were reviewed for VTE rates in lenalidomide-treated multiple myeloma. Results: VTE rates were 8.5% to 75% in multiple myeloma treated with lenalidomide and dex or erythropoietin; rates were <3.4% when aspirin prophylaxis was added. The FDA approved package insert for lenalidomide preemptively includes a black box warning describing high VTE rates with off-label use of lenalidomide and advises physicians that VTE prophylaxis should be considered, although the effectiveness of various prophylaxis regimens is unknown. Conclusions: Six months after the attorney general requested that a black box warning describe high VTE rates with off-label use of thalidomide, the manufacturer preemptively included an analogous black box warning in the package insert for the thalidomide analogue, lenalidomide, but did not include similar warnings for this toxicity in the package insert for thalidomide. The FDA should require that package inserts describe severe toxicities that commonly occur with off-label use of cancer therapies. This is especially important for severe class-related toxicities such as lenalidomide- and thalidomide- associated VTE. [Table: see text] No significant financial relationships to disclose.
When are medical apps medical? Off-label use and the Food and Drug Administration
