ldelalisib

Common name: Idelalis

Trade name: Zydelig

All names: Idelalis, Idelalisib, Zydelig

Indications:

1. For patients with relapsed chronic lymphocytic leukemia (CLL) in combination with rituximab, rituximab alone will be considered for appropriate treatment due to other comorbidities.

2. Patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) who have received at least 2 previous systemic treatments.

3. Patients with relapsed small lymphocytic lymphoma (SLL) who have received at least 2 previous systemic treatments.

Usage and dosage:

150 mg orally, 2 times a day.

Adverse reactions:

The most common adverse reactions (incidence ≥20%) are diarrhea, fever, fatigue, nausea, cough, pneumonia, abdominal pain, chills, and rash.

The most common laboratory abnormalities (incidence ≥30%) are neutropenia, hypertriglyceridemia, hyperglycemia, elevated ALT (alanine aminotransferase), and elevated AST (aspartate aminotransferase).

Contraindications:

A history of severe allergic reactions including anaphylaxis and toxic epidermal cell necrosis.

Notes:

Hepatotoxicity: AST/ALT (aspartate aminotransferase/alanine aminotransferase) should be tested every two weeks during the first three months of treatment; in the subsequent three months, AST/ALT should be tested every four weeks ; Test AST/ALT every 1-3 months for the next three months. When AST/ALT exceeds 3 times the upper limit of normal, monitor hepatotoxicity every week until symptoms are relieved; when AST/ALT exceeds 5 times the upper limit of normal, stop medication and continue to monitor AST, ALT, and bilirubin until symptoms disappear.

Severe diarrhea or colitis: Avoid using Zydelig with other drugs that can cause diarrhea. Diarrhea occurs because Zydelig rarely responds to anti-motility medications. Relief time ranges from one week to one month after stopping the drug or taking corticosteroids.

Pneumonia: If patients taking Zydelig present with extrapulmonary symptoms such as cough, dyspnea, hypoxia, interstitial infiltration in the radiology department, or oxygen saturation reduced by more than 50%, physicians should consider whether pneumonia has occurred. When pneumonia is suspected, discontinue medication until the cause of extrapulmonary symptoms is confirmed. Patients with pneumonia caused by Zydelig need to stop taking the drug and inject steroids to recover.

Intestinal perforation: When perforation occurs, some patients will experience moderate to severe diarrhea. Advise patients to promptly report any new or worsening abdominal pain, chills, fever, nausea, or vomiting that occurs at any time. In patients who develop bowel perforation, permanently discontinue the drug.

Serious skin reactions: In a clinical trial, Zydelig was associated with toxic epidermal necrolysis (TEN) when combined with rituximab and bendamustine. Other serious skin reactions include exfoliative dermatitis, rash, erythematous rash, etc. For patients who experience skin reactions, pay close attention to the patient's physical condition and stop taking the medication.

Systemic allergic reaction: During the medication, cases of systemic allergic reaction have occurred. When a patient experiences an allergic reaction, permanently discontinue the medication and take appropriate supportive measures.

Neutopenia: Check blood counts at least every two weeks for the first 3 months of treatment. When the neutrophil count is less than 1.0 Gi/L, test it at least once a week.

Lethal embryotoxicity: Women of childbearing potential are advised to avoid becoming pregnant while taking Zydelig. Use effective contraceptive measures while taking the medicine and within one month after stopping the medicine.

Storage:

Store at 20–30 °C (68–86 °F) except 15–30 ºC (59–86 ºF).

Mechanism of action:

Idelalisib is an inhibitor of PI3Kδ kinase expressed in normal and malignant B-cells. Idelalisib induces apoptosis and inhibits proliferation of malignant B-cell cell lines and primary tumor cells. Idelalisib inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and CXCR4 and CXCR5 signaling, which are involved in B-cell trafficking and homing to lymph nodes and bone marrow. Treatment of lymphoma cells with idelalisib resulted in inhibition of chemotaxis and adhesion, and reduced cell viability.

Safety and efficacy:

Idelalisib is the first-generation oral PI3Kδ inhibitor, which has significant clinical activity in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL). A study published in Blood aimed to evaluate the efficacy of the drug in the initial treatment of 64 patients (median age 71 years) with refractory/relapsed CLL or small lymphocytic leukemia. The researchers gave subjects rituximab 375 mg/m2 once a week for 8 weeks and Zydelig 150 mg twice a day for 48 weeks. The median treatment time was 22.4 months. The results showed that the overall response rate (ORR) was 97%, of which 19% were complete responses. The ORR of patients with del(17p)/TP53 mutations was 100%, and the ORR of patients without IGHV mutations was 97%. The 36-month progression-free survival rate was 83%.

This study shows that Idelalisib combined with rituximab has excellent efficacy in the treatment of elderly CLL and can sustainably control the disease. These findings also further confirm the clinical activity of idelalis as initial therapy for the treatment of CLL. u2003