Rapid disease progression following discontinuation of ibrutinib in patients with chronic lymphocytic leukemia treated in routine clinical practice

• Published in: Leukemia & lymphoma 2019-09, Vol.60 (11), p.2712-2719
• Main Authors: Hampel, Paul J., Ding, Wei, Call, Timothy G., Rabe, Kari G., Kenderian, Saad S., Witzig, Thomas E., Muchtar, Eli, Leis, Jose F., Chanan-Khan, Asher A., Koehler, Amber B., Fonder, Amie L., Schwager, Susan M., Slager, Susan L., Shanafelt, Tait D., Kay, Neil E., Parikh, Sameer A.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Chronic lymphocytic leukemia (CLL); discontinuation; Disease Progression; Drug-Related Side Effects and Adverse Reactions - etiology; Drug-Related Side Effects and Adverse Reactions - mortality; Drug-Related Side Effects and Adverse Reactions - pathology; Female; Follow-Up Studies; Humans; ibrutinib; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - mortality; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Male; Middle Aged; Practice Patterns, Physicians' - standards; Prognosis; progression; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Pyrazoles - administration & dosage; Pyrazoles - adverse effects; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Retrospective Studies; Survival Rate; Withholding Treatment - statistics & numerical data
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/10428194.2019.1602268

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.