Acalabrutinib, as a BTK inhibitor, has a different onset time due to individual differences and disease types. It usually requires continuous medication to observe clinical effects, especially for chronic lymphocytic leukemia and mantle cell lymphoma, which have significant therapeutic effects.

1. Core mechanism of action

(1) Targeted inhibition: Specifically covalently bind to the C481 residue of BTK, block the BCR signaling pathway, and inhibit malignant B cell proliferation.

(2) High selectivity: Compared to the first generation BTK inhibitors, it has lower off target effects on EGFR/ITK and reduces adverse reactions.

2. Characteristics of Drug Mechanisms of Action

(1) Inhibition of B cell receptor signaling pathway through irreversible binding to BTK targets.

(2) The peak blood drug value is reached 1-3 hours after oral administration, with a half-life of about 1 hour.

(3) Continuous administration is required to maintain the inhibitory effect on the target.

3 common observation times for therapeutic effects

(1) Patients with mantle cell lymphoma typically exhibit lymph node shrinkage within 2-4 weeks.

(2) Chronic lymphocytic leukemia requires 4-8 weeks to observe a decrease in peripheral blood lymphocytes.

(3) Complete remission usually requires continuous treatment for 3-6 months.

4 factors affecting the onset time

(1) The size of tumor burden directly affects response speed.

(2) Previous treatment history affects drug sensitivity.

(3) The combined use of CYP3A4 inhibitors may accelerate their effectiveness.

5 Advantages and Characteristics of Treatment

(1) Safety: The incidence of bleeding events and atrial fibrillation is significantly lower than that of first generation BTK inhibitors.

(2) Convenient administration: Oral twice a day, no need to adjust dosage based on body weight, and bioavailability is not affected by food.

6. Precautions related to therapeutic efficacy

(1) Drug resistance monitoring: Attention should be paid to drug resistance caused by BTKC481S mutation, which can be detected dynamically through ctDNA.

(2) Special population: Patients with severe liver function impairment need to reduce their dosage, and are prohibited during pregnancy (animals show embryotoxicity).