Idelalisib(Zydelig) is an oral drug targeting PI3Kδ kinase that provides an important second-line treatment option for patients with relapsed chronic lymphocytic leukemia (CLL). Its unique mechanism and combination regimen require rigorous clinical management to balance efficacy and risk.

Efficacy of Idelalisib (Zydelig) in Relapsed Chronic Lymphocytic Leukemia

By inhibiting the PI3Kδ signaling pathway, Idelalisib blocks the survival and proliferation of malignant B cells, and significantly improves the survival outcomes of selected CLL patients.

Mechanism of action and clinical data

Idelalisib targets PI3Kδ kinase, reduces tumor cell dependence on the microenvironment, and delays disease progression. Clinical trials have shown objective response rates (ORRs) of 85% to 90% and median progression-free survival (PFS) of more than 20 months when combined with rituximab. However, it is not clearly suitable for follicular lymphoma or first-line therapy, and is limited to patients with relapsed CLL who cannot tolerate other therapies due to comorbidities.

Indication Limitations and Patient Screening

Idelalisib' use of second-line therapy for relapsing CLL is strictly limited, and first-line therapy should be excluded. In the combination regimen, patients should be free of severe infection or active liver disease. Elderly patients (≥ 65 years old) account for 55% of patients, but due to the high rate of discontinuation of adverse effects, tolerability needs to be assessed individually. Gilead's original drug is 150mg×60 tablets, and has not yet been marketed in China.

Treatment should be continued until disease progression or intolerable toxicity, and the dose can be retaken within 6 hours of missed dose. In case of severe adverse reactions, the dose can be reduced to 100mg twice a day, and the drug can be permanently discontinued if there is a recurrence.

Contraception when using Zydelig

Idelalisib is embryo-fetal toxic and requires strict contraception to reduce the risk of pregnancy.

Contraceptive requirements for female patients

Women of childbearing potential should be confirmed to be pregnant prior to treatment and use highly effective contraception (eg, oral contraceptive barrier method) during treatment and for 1 month after the last dose. It is contraindicated in lactating women because the drug may cause serious adverse effects on the infant through breast milk.

Contraceptive norms for male patients

Men of childbearing potential should use a condom during treatment and for 3 months after the last dose to avoid unwanted pregnancy. If your partner becomes pregnant, stop the drug immediately and consult a geneticist.

Use during pregnancy may cause fetal malformations or miscarriage and is absolutely contraindicated for pregnant women. If pregnancy is suspected during treatment, immediate medical evaluation is required.

Effect of Adelalis on liver and kidney function

Idelalisib may pose risks related to hepatotoxicity and renal function, and needs to be monitored throughout the process to ensure the safety of treatment.

Hepatotoxicity management and monitoring

Severe hepatotoxicity occurred in 16% of patients, with ALT/AST elevated more than 5 times the upper limit of normal, mostly in the 12 weeks prior to treatment. Patients with abnormal liver function at baseline (ALT/AST>2.5 times or bilirubin>1.5 times the normal value) should be used with caution. During treatment, liver enzymes should be monitored every 2 weeks, and if abnormal, the drug should be suspended until recovery. Recurrent hepatotoxicity requires permanent discontinuation.

Medication restriction in patients with renal impairment

There are limited data on the effect of Idelalisib on renal function, and the dose is not recommended for patients with an eGFR≥60mL/min/1.73m², and not recommended for patients with an eGFR<60mL/min. Serum creatinine and urine output should be monitored during treatment, and if acute kidney injury develops, medication should be discontinued and the cause should be evaluated.

The drug should be stored at 15-30°C, away from light and moisture. If jaundice, dark urine or edema develops during treatment, seek immediate medical attention. Elderly patients and patients with hepatic and renal insufficiency should be followed up more frequently.

Standardized use of Idelalisib requires a combination of multidisciplinary collaboration, and regular re-examination of liver and kidney function and blood counts is the key to reducing risk. Patients should strictly follow the doctor's instructions and report adverse reactions in a timely manner to optimize treatment outcomes and ensure long-term safety.