| Regimen | Clinical considerations |
BTK inhibitor: - Acalabrutinib
- Zanubrutinib
- Ibrutinib
| - Oral medication.
- Administered as continuous therapy.
- Increases the risk for bleeding, atrial fibrillation, and hypertension.
- Other toxicities: fatigue, rash, infections, and myalgia/arthralgia.
- All are CYP3A4 substrates, contributing to numerous drug interactions; generally avoid with strong CYP3A4 inhibitors or inducers. Use with caution in patients on anticoagulation, especially warfarin.
- May be preferred over venetoclax plus obinutuzumab in patients with kidney impairment; kidney impairment increases the risk of TLS with venetoclax.
- Acalabrutinib and zanubrutinib are preferred over ibrutinib as they are at least as effective and better tolerated.
|
| Venetoclax plus obinutuzumab | - Combination of oral medication (venetoclax) and intravenous medication (obinutuzumab).
- Administered for a fixed duration (12 months).
- Allows for retreatment at the time of progression.
- Requires risk-based TLS prophylaxis and monitoring.
- Most common toxicities: neutropenia, thrombocytopenia, anemia, diarrhea, nausea, upper respiratory tract infection, cough, musculoskeletal pain, fatigue, and edema.
- Clinically significant TLS is rare with proper precautions.
- Avoided in patients on nephrotoxic drugs and those taking a strong CYP3A4 inhibitor, as both can increase the risk for TLS with venetoclax (a CYP3A4 substrate); also avoid use with moderate or strong CYP3A4 inducers.
- May be preferred over a BTK inhibitor in those with cardiovascular disorders, uncontrolled hypertension, and/or a high risk for bleeding.
- Cross-trial comparisons suggest decreased efficacy in patients with del17p or TP53 mutation.
|
| Ibrutinib plus venetoclax | - All-oral regimen.
- Administered for a fixed duration (15 months).
- Allows for retreatment at the time of progression.
- Requires risk-based TLS prophylaxis and monitoring but is logistically easier than with venetoclax plus obinutuzumab.
- Most common toxicities: neutropenia, diarrhea, and hypertension.
- Clinically significant TLS is rare.
- Both are CYP3A4 substrates, contributing to numerous drug interactions; generally avoid in patients taking strong CYP3A4 inhibitors or moderate or strong CYP3A4 inducers.
- Less preferred in patients with conditions that make them poor candidates for a BTK inhibitor (eg, cardiovascular disorders, uncontrolled hypertension, and/or high risk for bleeding).
- Limited data in patients with del17p or TP53 mutation.
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