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Ferrata Storti Foundation
Chronic Lymphocytic Leukemia
Toxicities and outcomes of 616 ibrutinib-treated patients in the United States: a real-world analysis
Anthony R. Mato,1 Chadhi Nabhan,2 Meghan C. Thompson,1 Nicole Lamanna,3 Danielle M. Brander,4 Brian Hill,5 Christina Howlett,6,7 Alan Skarbnik,7 Bruce D. Cheson,8 Clive Zent,9 Jeffrey Pu,10 Pavel Kiselev,11 Andre Goy,7 David Claxton,10 Krista Isaac,12 Kaitlin H. Kennard,1 Colleen Timlin,1 Daniel Landsburg,1 Allison Winter,5 Sunita D. Nasta,1 Spencer H. Bachow,3 Stephen J. Schuster,1 Colleen Dorsey,1 Jakub Svoboda,1 Paul Barr13* and Chaitra S. Ujjani8*
Haematologica 2018 Volume 103(5):874-879
1Hematology and Oncology, University of Pennsylvania, Philadelphia, PA; 2Cardinal Health, Dublin, OH 3Hematology/Oncology, Presbyterian/Columbia University Medical Center, New York, NY; 4Hematology/Oncology, Duke University, Durham, NC; 5Hematology and Medical Oncology, Cleveland Clinic, OH; 6Pharmacy, Ernest Mario School of Pharmacy, New Brunswick, NY; 7Hematology/Oncology, John Theurer Cancer Center, Hackensack, NY; 8Hematology/Oncology, Georgetown University Hospital, Washington DC; 9Hematology/Oncology, University of Rochester Medical Center, NY; 10Hematology/Oncology, Penn State Milton S Hershey Medical Center, PA; 11Lymphoma, Celgene Corp, Summit, NY; 12Hematology/Oncology, Lankenau Hospital, Wynnewood, PA and 13Division of Hematology and Oncology, University of Rochester, NY, USA
*Indicates shared last authorship
ABSTRACT
Clinical trials that led to ibrutinib’s approval for the treatment of chronic lymphocytic leukemia showed that its side effects differ from those of traditional chemotherapy. Reasons for discontinua- tion 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 com- pare the type and frequency of toxicities reported in either setting, assess discontinuation rates, and evaluate outcomes. This multicenter, retrospec- tive analysis included ibrutinib-treated chronic lymphocytic leukemia patients at nine United States cancer centers or from the Connect® Chronic Lymphocytic Leukemia Registry. We examined demographics, dosing, discontinuation rates and reasons, toxicities, and outcomes. The primary endpoint was progression-free survival. Six hundred sixteen ibru- tinib-treated patients were identified. A total of 546 (88%) patients were treated with the 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 41% of patients discontin- ued ibrutinib (median time to ibrutinib discontinuation was 7 months). Notably, ibrutinib toxicity was the most common reason for discontinua- tion in all settings. The median progression-free survival and overall sur- vival for the entire cohort were 35 months and not reached (median fol- low-up 17 months), respectively. In the largest reported series on ibrutinib- treated chronic lymphocytic leukemia patients, we show that 41% of patients discontinued ibrutinib. Intolerance as opposed to chronic lympho- cytic leukemia progression was the most common reason for discontinua- tion. Outcomes remain excellent and were not affected by line of therapy or whether patients were treated on clinical studies or commercially. These data strongly argue in favor of finding 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.
Correspondence:
amato@mskcc.org
Received: October 20, 2017. Accepted: January 26, 2018. Pre-published: February 1, 2018.
doi:10.3324/haematol.2017.182907
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/5/874
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