Ibrutinib-associated tumor lysis syndrome in chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma: A case series and review of the literature.

Background Tumor lysis syndrome results when intracellular contents are released during cell lysis. Ibrutinib, a Bruton tyrosine kinase inhibitor, is used for the treatment of chronic lymphocytic leukemia, small lymphocytic lymphoma, Waldenström's macroglobulinemia, mantle cell lymphoma, and marginal zone lymphoma. Tumor lysis syndrome caused by ibrutinib therapy is potentially life threatening, but is rare and not often reported in clinical trials. Objective The purpose of this case series is to describe the occurrence of tumor lysis syndrome in two patients initiated on ibrutinib, and to highlight the importance of close monitoring during therapy. Discussion One patient with chronic lymphocytic leukemia/small lymphocytic lymphoma and one patient with mantle cell lymphoma developed laboratory and clinical tumor lysis syndrome following initiation of ibrutinib therapy. Assessment with the Naranjo Adverse Drug Reaction Probability Scale indicated one probable relationship and one possible relationship between ibrutinib therapy and tumor lysis syndrome. There were additional factors that may have confounded the laboratory and clinical factors observed, including baseline laboratory values and concurrent medications. Both patients were managed with supportive therapies. A literature review identified five additional reported cases of tumor lysis syndrome following ibrutinib therapy. Conclusion This case series identifies one patient with a probable relationship and one patient with a possible relationship between the development of tumor lysis syndrome and treatment with ibrutinib. Although uncommon, proper attention should be given to monitoring for this adverse drug reaction and appropriate follow-up should occur despite ibrutinib's ease of administration.

Effect of selected clinical trial publication on adjunctive nonstatin medication prescribing in the Veterans Health Administration system.

PURPOSE: The question of whether publication of selected clinical trials is temporally followed by changes in prescribing of adjunctive lipid-lowering medications was evaluated. METHODS: In this retrospective preanalysis and postanalysis, Veterans Health Administration (VHA) patients 18 years or older who received a new or renewed order for any lipid-lowering medication between April 2, 2004, and September 2, 2014, were included. This period was chosen based on the publication dates of three trials investigating the efficacy of nonstatin medications: Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia (ENHANCE, April 3, 2008), Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus (ACCORD Lipid, March 14, 2010), and Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy (AIM-HIGH, December 15, 2011). Annual prescribing rates for ezetimibe, fibrates, and niacin were analyzed for 4 years before and after the ENHANCE, ACCORD, and AIM-HIGH trial publication dates, respectively (3 years for niacin in AIM-HIGH) and reported as percent of patients in the cohort. RESULTS: Among patients receiving lipid-lowering medications, relatively low overall prescribing rates were observed for all three target medications. Prescribing rates for each medication decreased after its respective trial publication, with ezetimibe having the greatest change. CONCLUSION: Prescribing of fibrates, niacin, and ezetimibe in the VHA system decreased after the publication of landmark trials assessing their addition to a statin, consistent with the recommendations in the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline, which did not encourage routine use of adjunctive therapies to lower the risk of cardiovascular disease.