Comprehensive explanation of the mechanism of action and clinical efficacy of Pitobrutinib/Pitobrutinib (Zepali)

Pitobrutinib/Pirtobrutinib (pirtobrutinib) is a new oral small molecule BTK (Bruton’s tyrosine kinase) inhibitor, mainly used to treat relapsed or refractory disease Bcell malignant tumors, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), etc. BTK is a key enzyme in the B cell receptor signaling pathway. It plays a central role in B cell proliferation, survival and migration. By selectively inhibiting the activity of BTK, pitubrutinib can block the signaling of abnormal B cells, thereby inhibiting the proliferation of malignant B cells and promoting their apoptosis. This mechanism enables it to show significant efficacy in patients with relapsed or refractory B cell tumors.

Compared with traditionalBTK inhibitors, pitubrutinib has highly selective and reversible inhibition characteristics. It not only targets BTK but is also effective against B cells that are resistant to C481 site mutations. This clinically solves the problem that some patients cannot continue to receive first-generation BTK inhibitor treatment due to drug resistance. Multiple clinical studies have shown that pitubrutinib can maintain a high level of disease control rate after long-term treatment, and its objective response rate can reach 50% in patients with relapsed or refractory CLLCLL pan>to 70%, and the progression-free survival (PFS) is significantly prolonged, providing an effective treatment option for high-risk patients.

In terms of clinical efficacy, the advantages of pitubrutinib are not only reflected in tumor control, but also in symptom improvement and quality of life. After patients use the drug, their lymph nodes shrink and their hematological indicators improve significantly, often accompanied by relief of symptoms such as anemia and thrombocytopenia. Pitobrutinib can still provide new treatment opportunities for patients who have previously received chemotherapy or other targeted drug treatments but had poor efficacy. Its oral administration method is also convenient for long-term use, allowing patients to complete continuous treatment without frequent hospitalization for infusions, which greatly improves patient compliance and life convenience.

In addition, pitubrutinib was well tolerated. Common adverse reactions include mild to moderate diarrhea, fatigue, rash or slight bleeding tendency, most of which can be controlled through dose adjustment or symptomatic treatment. Compared with earlier BTK inhibitors, its cardiovascular and blood pressure effects are smaller, reducing safety risks during treatment. Doctors can optimize the dose based on the patient's weight, liver and kidney function, and previous medication history to achieve an individualized treatment plan. At the same time, the drug has good pharmacokinetic properties and stable blood concentration, and can maintain long-term effective inhibition of the BTK signaling pathway and delay disease progression.

Taken together, Pitobrutinib/Pitobrutinib inhibits abnormal BBTK signaling pathway. an>cell proliferation not only solves the resistance problem of some first-generation BTK inhibitors, but also shows significant efficacy in patients with relapsed or refractory B cell tumors. Its oral administration, good tolerability and efficacy in patients with high-risk mutations make it valuable in clinical treatment options. With the accumulation of more long-term follow-up data, Pitobrutinib is expected to further optimize the treatment model for B cell malignancies and provide patients with a safer, more effective, and personalized long-term management plan.

Reference:https://en.wikipedia.org/wiki/Pirtobrutinib