Lenalidomide as a Novel Therapy for Gastrointestinal Angiodysplasia

Abstract

Purpose: Lenalidomide is a thalidomide analog with anti-angiogenic properties. Anecdotal literature limited to case reports suggests its use for the prevention of gastrointestinal bleeding (GIB) secondary to angiodysplasia and potential reversal of angiodysplasia. We present, to our knowledge, the first case series to explore Lenalidomide as a first-line therapy for this purpose. Methods: A retrospective chart review from 2010 through 2013 of patients meeting inclusion criteria was undertaken. Patients with recurrent GIB secondary to angiodysplasias and previous failure of single-agent use of anti-fibrinolytic agents were included in this study. Antifibrinolytics were stopped upon initiation of Lenalidomide due to possible potentiation of thrombotic risk. Exclusion criteria were leukopenia, lymphoma, solid tumor disease, prior thromboembolic disease, or any underlying cytopenia not explained by blood loss. Results: We evaluated five patients (three males; 68.2±4.9 years) who met the inclusion criteria. Sites of angiodysplasia included the stomach, duodenum, jejunum, and colon. All five patients had von Willebrand's disease (three with type 3 and one each with types 1 and 2a). One patient had concurrent Osler-Weber-Rendu disease. The starting dose of Lenalidomide was 5 mg orally per day in all patients. Up-titration to 10 and 15 mg in one patient each was necessary due to recurrence of GIB. The mean number of endoscopies performed for control of GIB post Lenalidomide therapy was significantly lower compared to pre-therapy (5.50 vs 0.25; p= 0.001). Bleed-free duration on Lenalidomide therapy was 12.6 ± 4.7 months. Three patients have reported no GIB since the initiation of therapy. Three patients reported fatigue as a side effect, one of whom also had constipation. Another patient was initially started on Thalidomide and was switched to Lenalidomide due to constipation and mood swings. The treatment was stopped in 1 patient due to excessive fatigue despite clinical improvement. This patient remained asymptomatic for 11 months before developing a recurrence of GIB. Another patient in whom therapy was discontinued due to side-effects developed upper GIB 1 month later. Lenalidomide was subsequently resumed and the patient has remained asymptomatic since. There was no mortality, rashes, peripheral paraesthesias, cytopenias, bleeding, or thrombotic complications. Conclusion: This case series demonstrates that in selected patients with von Willebrand's disease and recurrent GIB from angiodysplasias, Lenalidomide therapy significantly reduced the number of endoscopies and increased the bleed-free duration. Prospective multicenter trials are needed to further define the role of Lenalidomide in the management of GIB from angiodysplasia.