Thalidomide-Associated Thromboembolism in Cancer: Reimbursement for Thalidomide’s “Off-Label” Prescribing under the 2004 Medicare Oral Pharmaceutical Demonstration Project Raises Concerns.

Purpose: In 1999, one year after its approval by the FDA for erythema nodosum leprosum, thalidomide’s effectiveness as an off-label treatment for multiple myeloma was noted. A 28% rate of thromboembolism with thalidomide-doxorubicin therapy for myeloma was reported in 2001. Thalidomide’s inclusion in the 2004 Medicare Oral Pharmaceutical Demonstration Project as treatment for multiple myeloma represents the only off-label use drug covered. FDA regulations prohibit manufacturer dissemination of comprehensive safety information describing thalidomide-associated thromboembolism (TAT) in the off-label oncology setting. Herein, we reviewed FDA and published information for TAT in the oncology setting.

Methods: Adverse event reports contained in FDA databases (n= 190 patients) and 48 prospective clinical trials (n= 2,329 patients) were reviewed for information on thromboembolism occurring among thalidomide-treated cancer patients.

Results: TAT occurred after a median of 52 days of therapy (range, 6 to 469 days), with more than half of these events among persons with multiple myeloma. TAT rates of 30% were noted among patients with newly diagnosed multiple myeloma receiving concomitant doxorubicin. Previously treated myeloma patients receiving thalidomide and doxorubicin and newly diagnosed patients on thalidomide, doxorubicin, and low molecular weight heparin had thromboembolism rates of 15% or lower.

Conclusions: Revision of FDA regulations to allow dissemination of information describing benefits and toxicities of thalidomide as an off-label cancer treatment is important, particularly for multiple myeloma patients receiving thalidomide under the 2004 Medicare Oral Pharmaceutical Demonstration Project.