Ibrutinib Dosing for Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma
For chronic lymphocytic leukemia (CLL), administer ibrutinib 420 mg orally once daily continuously until disease progression; for mantle cell lymphoma (MCL), the standard dose is 560 mg orally once daily. 1, 2
Standard Dosing Regimens
Chronic Lymphocytic Leukemia
- 420 mg orally once daily, taken continuously without interruption until disease progression 1
- Continue treatment indefinitely as long as the patient is responding and tolerating therapy 1
- This dosing applies to both treatment-naive and relapsed/refractory CLL patients 1
Mantle Cell Lymphoma
- 560 mg orally once daily until disease progression 2, 3
- The higher dose for MCL compared to CLL is based on FDA approval and clinical trial data 2, 4
Critical Management Considerations
Expected Lymphocytosis
- Do not mistake transient lymphocytosis for disease progression 1
- Expect an increase in absolute lymphocyte count during the first few weeks of therapy in most CLL patients 1
- This lymphocytosis may persist for several weeks but does not indicate treatment failure 1
Perioperative Management
- Hold ibrutinib 3 days before and after minor surgical procedures 1
- Hold ibrutinib 7 days before and after major surgical procedures 1
- This minimizes bleeding risk given ibrutinib's antiplatelet effects 1
Drug Interactions Requiring Dose Modification
- Avoid concomitant strong CYP3A inhibitors (ketoconazole, itraconazole, clarithromycin) 1, 2
- For short-term strong CYP3A inhibitors (≤7 days): interrupt ibrutinib during inhibitor use 1
- Avoid concomitant strong CYP3A inducers (rifampin, carbamazepine, phenytoin, St. John's Wort) as they decrease ibrutinib levels 1, 2
- Avoid grapefruit and Seville oranges during treatment 2
Anticoagulation Precautions
- Never administer ibrutinib concomitantly with warfarin 1
- Consider non-warfarin anticoagulation if anticoagulation is required 1
- Carefully weigh benefit-risk in patients requiring antiplatelet or anticoagulant therapies 1
Common Adverse Events and Management
Atrial Fibrillation
- Occurs in 6-9% of patients 1
- Monitor patients carefully for new-onset atrial fibrillation 1
- Consider non-warfarin anticoagulation if anticoagulation is needed 1
- Switch to alternative therapy (such as idelalisib) if atrial fibrillation is recurrent and not medically controllable 1
Hypertension
- Manage with antihypertensive medications as appropriate 1
- Only discontinue ibrutinib for uncontrollable hypertension 1
- Hypertension is uncommonly reported as a basis for discontinuation 1
Bleeding Risk
- Most adverse events are mild (grades 1-2), including diarrhea, fatigue, pyrexia, and nausea 1
- Monitor for bleeding complications, particularly in patients on antiplatelet agents 1
Transitioning at Disease Progression
When CLL progresses on ibrutinib, transition to next therapy as soon as possible since progression may accelerate when ibrutinib is stopped 1
- Keep the treatment-free interval as short as possible 1
- This is critical to prevent rapid disease acceleration after stopping ibrutinib 1
Efficacy Data Supporting Dosing
CLL Evidence
- In the RESONATE study, ibrutinib 420 mg daily demonstrated median PFS not reached versus 8.1 months for ofatumumab 1
- Hazard ratio for death was 0.43 (57% reduction in risk of death) 1
- Five-year follow-up confirmed 5-year PFS rate of 70% versus 12% for chlorambucil in treatment-naive patients ≥65 years 1