Rapid disease progression following discontinuation of ibrutinib in patients with chronic lymphocytic leukemia treated in routine clinical practice.
We identified all patients with chronic lymphocytic leukemia at Mayo Clinic treated with ibrutinib outside the context of a clinical trial; timing and reasons for discontinuation were ascertained, as were symptoms, exam and radiographic findings, and laboratory changes following discontinuation. Of 202 patients who received ibrutinib, 52 discontinued therapy (estimated 1- and 2-year risk of discontinuation 18% and 28%, respectively). The most common reasons for discontinuation were toxicity (56%) and progression of disease (32%, including Richter's transformation in 15%). Rapid progression of disease within 4 weeks after discontinuation was observed in 9/36 (25%) patients with adequate records for review, mostly in those stopping ibrutinib for disease progression (n = 8) rather than toxicity (n = 1). This was evident by sudden worsening of disease-related symptoms (n = 9), exam/radiographic changes (n = 7), and laboratory changes (n = 8). An estimated one in every three patients discontinued ibrutinib by 2 years, with 25% developing rapid disease progression afterwards.
['Hampel|Paul J|PJ|0000-0003-1292-3024', 'Ding|Wei|W|', 'Call|Timothy G|TG|', 'Rabe|Kari G|KG|', 'Kenderian|Saad S|SS|', 'Witzig|Thomas E|TE|', 'Muchtar|Eli|E|0000-0003-2210-2174', 'Leis|Jose F|JF|', 'Chanan-Khan|Asher A|AA|', 'Koehler|Amber B|AB|', 'Fonder|Amie L|AL|', 'Schwager|Susan M|SM|', 'Slager|Susan L|SL|', 'Shanafelt|Tait D|TD|', 'Kay|Neil E|NE|', 'Parikh|Sameer A|SA|']
D000225:Adenine D000328:Adult D000368:Aged D000369:Aged, 80 and over D018450:Disease Progression D064420:Drug-Related Side Effects and Adverse Reactions D005260:Female D005500:Follow-Up Studies D006801:Humans D015451:Leukemia, Lymphocytic, Chronic, B-Cell D008297:Male D008875:Middle Aged D010880:Piperidines D010818:Practice Patterns, Physicians' D011379:Prognosis D047428:Protein Kinase Inhibitors D011720:Pyrazoles D011743:Pyrimidines D012189:Retrospective Studies D015996:Survival Rate D028761:Withholding Treatment
progression discontinuation ibrutinib Chronic lymphocytic leukemia (CLL)