Real-World Ibrutinib dose Reductions, Holds and Discontinuations in Chronic Lymphocytic Leukemia

Abstract

Aim: A retrospective chart review of ibrutinib-treated patients with chronic lymphocytic leukemia (CLL) was conducted. Patients & methods: Adults with CLL who initiated ibrutinib were followed for ≥6 months (n = 180). Results: Twenty-five percent of first-line ibrutinib patients experienced ≥1 dose reduction, mainly due to adverse events (AEs; 79%). Treatment discontinuations and dose holds occurred in 20 and 34% of patients, respectively, most commonly due to AEs (73 and 74%). Approximately one-quarter of relapsed/refractory ibrutinib patients experienced ≥1 dose reduction, mainly due to AEs (88%). Treatment discontinuation and dose holds occurred in 40% of patients (58 and 76% due to AEs, respectively). Conclusion: Dose reductions, holds and discontinuations were frequent in patients with CLL receiving ibrutinib in routine clinical practice.

Managing Ibrutinib-Intolerant Patients With B-Cell Malignancies

“… 20 , 23 In a real-world study investigating dose reductions or discontinuations in patients with CLL, 22.8% of patients experienced a dose reduction and 20.6% discontinued ibrutinib due to an adverse event (AE). 30 In this study, the most common AEs leading to discontinuation of ibrutinib were atrial fibrillation (24% of patients who discontinued ibrutinib), gastrointestinal disorders (24%), infections/infestations (19%), hematologic abnormalities (16%), and fatigue (14%). In another real-world study of ibrutinib in patients with CLL, 91/209 (43.5%) patients had a temporary dose interruption, and after a median of 20 months on therapy, 37/209 (17.7%) patients discontinued therapy due to a toxicity, including infection (21.6%), cardiovascular event (13.5%), hematologic toxicity (13.5%), bleeding (10.8%), atrial fibrillation (8.1%), diarrhea (8.1%), musculoskeletal pain (5.4%), or other (18.9%).…”

Management of relapsed/refractory Chronic Lymphocytic Leukemia

“…A large multicenter retrospective study of 231 patients treated in the relapsed setting showed a discontinuation rate of 20.9% due to toxicity, with atrial fibrillation, infection, pneumonitis, bleeding, and diarrhea being the most common toxicities leading to discontinuation 5 . Another US based study and data from the Swedish CLL group also showed a discontinuation rate of around 20% due to toxicity 6,7 …”

“… 5 Another US based study and data from the Swedish CLL group also showed a discontinuation rate of around 20% due to toxicity. 6 , 7 …”

Assessment of ibrutinib scheduling on leukocyte, lymph node size and blood pressure dynamics in chronic lymphocytic leukemia through pharmacokinetic‐pharmacodynamic models

“…2 Retrospective analyses have shown that dose reductions of ibrutinib to 140-280 mg day −1 within 3 months from treatment initiation, due to adverse events or other causes, can minimize the adverse events without having inferior outcomes on long-term therapy. [3][4][5][6] CLL is a form of leukemia, with diverse biological and clinical characteristics. 7 The disease is characterized by abnormal B-lymphocyte accumulation in lymphoid tissues and blood.…”