Acalabrutinib Dosing and Combination Regimens: CLL/SLL, MCL, Safety Adjustments

　　1.Routine Administration and Base Dose

　　Acalabrutinib is an oral BTK inhibitor.The usual adult base dose is 100mg approximately every 12 hours.Swallow the capsule or tablet whole with water;do not open,crush,chew,or dissolve.It may be taken with or without food.If a dose is missed by more than about 3 hours,skip it and take the next scheduled dose;do not double.

　　For monotherapy in CLL,SLL,or previously treated MCL,continue until disease progression or unacceptable toxicity rather than stopping after a fixed number of cycles.

　　2.CLL/SLL Monotherapy

　　Adults with chronic lymphocytic leukemia or small lymphocytic lymphoma who are eligible for single-agent therapy use 100mg twice daily.Duration is driven by disease control and tolerability,with regular assessment of blood counts,nodes,infection risk,and symptoms.

　　3.Previously Untreated CLL/SLL with Obinutuzumab

　　Start acalabrutinib at cycle 1,100mg twice daily.Start obinutuzumab at cycle 2 for 6 cycles using its standard dosing.On same-day administration,give acalabrutinib before obinutuzumab.Acalabrutinib is continued until progression or unacceptable toxicity;if venetoclax or other agents are added,total cycle count follows that specific regimen.

　　4.Previously Untreated MCL with Bendamustine and Rituximab

　　For adults with newly diagnosed mantle cell lymphoma who are ineligible for autologous stem cell transplant,use acalabrutinib starting day 1 of cycle 1 at 100mg twice daily until progression or unacceptable toxicity.Give bendamustine per protocol on days 1–2 and rituximab on day 1,typically for 6 cycles.Patients who achieve partial or complete response after the first 6 cycles may be evaluated for rituximab maintenance per the overall plan.

　　5.Adverse Events and Dose Modification

　　Hold acalabrutinib for severe/opportunistic infection,significant bleeding,grade 3–4 non-hematologic toxicity,grade 3 thrombocytopenia with bleeding,grade 4 thrombocytopenia,grade 4 neutropenia lasting over 7 days,arrhythmia,or notable hepatotoxicity.After recovery to grade 1 or baseline,restart at 100mg twice daily,reduce to 100mg once daily,or discontinue based on recurrence count and severity.

　　Monitor CBC,LFTs,and infection signs throughout.Pay extra attention to atrial fibrillation/flutter,hypertension,bleeding risk,and concurrent anticoagulants/antiplatelets.

　　6.Drug Interactions

　　Strong CYP3A inhibitors:avoid;for short courses such as certain anti-infectives up to about 7 days,interrupt acalabrutinib and resume 24 hours after stopping the inhibitor.

　　Moderate CYP3A inhibitors:consider 100mg once daily with close monitoring.

　　Strong CYP3A inducers:avoid;if unavoidable,increase to 200mg twice daily.

　　Acid reducers:avoid PPIs with capsule formulations;take H2 antagonists about 2 hours before acalabrutinib and separate antacids by at least 2 hours.Some film-coated tablet formulations allow PPI/H2/antacid co-use—follow the specific product label.

　　Do not add CYP3A-affecting antifungals,anti-epileptics,anti-TB drugs,St John’s wort,or other agents without review.