Colleen Dorsey, Krista Isaack, Sunita D Nasta, Colleen Timlin, Brian Hill, David Claxton, Christina Howlett, Danielle M Brander, Kaitlin H Kennard, Jakub Svoboda, Daniel Landsburg, Paul Barr, Alan Skarbnik, Chaitra S Ujjani, Chadi Nabhan, Clive Zent, Nicole Lamanna, Andre Goy, Jeffrey Pu, Bruce D Cheson, Allison Winter, Pavel Kiselev, Spencer H Bachow, Anthony R Mato, Stephen J Schuster, Meghan C Thompson
Clinical trials that led to ibrutinib's approval in chronic lymphocytic leukemia showed that its side effects differ from traditional chemotherapy toxicities. Reasons for discontinuation in clinical practice have not been adequately studied. We conducted a retrospective analysis of chronic lymphocytic leukemia patients treated with ibrutinib either commercially or on clinical trials. We aimed to compare the type and frequency of toxicities reported in either setting, assess discontinuation rates, and evaluate outcomes. This multicenter, retrospective analysis included ibrutinib-treated chronic lymphocytic leukemia patients at 9 United States cancer centers or the Connec Chronic Lymphocytic Leukemia Registry. We examined demographics, dosing, discontinuation rates and reasons, toxicities, and outcomes. The primary endpoint was progression-free survival. 621 ibrutinib-treated patients were identified. A total of 546 (88%) patients were treated with commercial drug. Clinical trial patients were younger (mean age 58 versus 61 years, p=0.01) and had a similar time from diagnosis to treatment with ibrutinib (mean 85 versus 87 months, p=0.8). With a median follow-up of 17 months, an estimated 42% of patients discontinued ibrutinib (median time to ibrutinib discontinuation was 7 months). Notably, ibrutinib toxicity was the most common reason for discontinuation in all settings. Median progression free survival and overall survival for the entire cohort were 35 months and not reached (median follow-up 17 months), respectively. In the largest reported series on ibrutinib-treated chronic lymphocytic leukemia patients, we show that 42% of patients discontinued ibrutinib. Intolerance as opposed to chronic lymphocytic leukemia progression was the most common reason for discontinuation. Outcomes remain excellent and were not impacted by line of therapy and whether patients were treated on clinical studies or commercially. These data strongly argue to find strategies to minimize ibrutinib intolerance so that efficacy can be further maximized. Future clinical trials should consider time-limited therapy approaches, particularly in patients achieving a complete response, in order to minimize ibrutinib exposure.
