When using Zydelig for the treatment of relapsed and refractory chronic lymphocytic leukemia (CLL), there are some important things that patients need to be aware of to ensure the safety and effectiveness of the drug and minimize potential adverse effects. Here are some things to look out for.

Notes on Idelalisib

Hepatotoxicity

Fatal and/or severe hepatotoxicity occurred in 16% of patients treated with the combination of Idelalisib and rituximab or with unapproved combination therapies. Elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 5 times the upper limit of normal has occurred. These results are usually observed during the first 12 weeks of treatment and are reversible after suspension of dosing. After restarting treatment at a lower dose, 26% of patients experienced recurrence of alanine aminotransferase and aspartate aminotransferase elevations. When hepatotoxicity recurs, Idelalisib is discontinued.

Avoid the combination of Idelalisib with other drugs that may cause liver toxicity.

Monitor alanine aminotransferase and aspartate aminotransferase in all patients every 2 weeks during the first 3 months of treatment, every 4 weeks in the next 3 months, and then every 1-3 months. If alanine aminotransferase or aspartate aminotransferase is elevated more than 3 times the upper limit of normal, hepatotoxicity is monitored weekly until remission. If alanine aminotransferase or aspartate aminotransferase exceeds 5 times the upper limit of normal, Idelalisib is discontinued, and weekly monitoring of alanine aminotransferase, alanine aminotransferase, and total bilirubin is continued until abnormal remission.

Severe diarrhea or colitis

Severe diarrhoea or colitis (grade 3 or above) occurred in 20% of patients treated with the combination of Idelalisib and rituximab or with an unapproved combination therapy. Diarrhea can occur at any time, and combinations of Idelalisib and other diarrhea-causing drugs should be avoided. Diarrhoea caused by Idelalisib did not respond well to antikinetic drugs, and the median time to adverse effects was 1 week to 1 month after suspension of treatment with Idelalisib, and corticosteroids in some cases, in all trials.

Pneumonia

Patients treated with Idelalisib developed fatal and severe pneumonia, and the clinical manifestations included interstitial infiltrates and organizing pneumonia. For patients taking Idelalisib, if pulmonary symptoms such as cough, dyspnea, hypoxia, interstitial infiltrates on radiological examination, or oxygen desaturation of more than 5% are present, treatment with Idelalisib is withheld until the cause is determined.

If symptomatic pneumonia or organizing pneumonia is diagnosed, treatment with appropriate corticosteroids should be started and Idelalisib should be permanently discontinued.

Infection

Forty-eight percent of patients treated with Idelalisib in combination with rituximab or with unapproved combination therapies developed fatal and/or serious infections, with the most common infections being pneumonia, sepsis, and febrile neutropenia. Infection should be treated prior to initiation of treatment with Idelalisib, and patients treated with Idelalisib should be monitored for signs and symptoms of infection, and treatment with Idelalisib should be suspended if grade 3 or higher infection develops.

The incidence of severe or fatal Pneumocystis jirovecii pneumonia (PJP) or cytomegalovirus (CMV) was <1% in patients treated with Idelalisib. Pneumocystis jirovecii pneumonia precautions should be taken during treatment with Pneumocystis jirovecii, and treatment with Pneumocystis jirovecii suspected of any grade should be suspended, and if Pneumocystis jirovecii infection of any grade is confirmed, treatment with Pneumocystis jiroveci should be permanently discontinued.

For patients with a history of CMV infection or positive CMV serology at the start of Idelalisib treatment, regular clinical and laboratory monitoring for CMV infection is recommended. In the setting of a positive CMV PCR or antigen test, treatment with Idelalisib is suspended until viremia resolves. If Idelalisibr is subsequently resumed, the patient should be monitored for CMV reactivation by PCR or antigen testing at least monthly.

Intestinal perforation

Patients treated with Idelalisib developed fatal and severe intestinal perforation, and some patients experienced moderate to severe diarrhea at the time of perforation. Patients are advised to promptly report any new or worsening abdominal pain, chills, fever, nausea, or vomiting, and to permanently discontinue Idelalisib in patients with intestinal perforation.

Severe skin reactions

Fatal cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have occurred in patients treated with Idelalisib, as well as cases of drug reactions with eosinophilia and systemic symptoms (DRESS).

Idelalisib is contraindicated in patients with a history of toxic epidermal necrolysis, and if Stevens-Johnson syndrome, toxic epidermal necrolysis or drug reaction with eosinophilia and systemic symptoms is suspected, treatment with Adelarius is suspended until the cause of the reaction is determined. If there is a confirmed diagnosis of Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms, Idelalisib is permanently discontinued.

Other severe or life-threatening (grade ≥3) skin reactions have also been reported in patients treated with Idelalisib, including exfoliative dermatitis, rash, erythematous rash, generalized rash, macules, maculopapular rash, papules, pruritic rash, exfoliative rash, and skin disease. Therefore, patients should be monitored for other severe or life-threatening skin reactions and permanently discontinued with Idelalisib.

Hypersensitivity

Patients who have been treated with Idelalisib have been reported to have severe hypersensitivity reactions, including anaphylactic shock. Idelalisib is contraindicated in patients with a history of severe hypersensitivity reactions to Idelalisib, including anaphylactic shock. In patients who develop severe hypersensitivity reactions, Idelalisib should be permanently discontinued and appropriate supportive measures should be taken.

Neutropenia

Grade 3 or 4 neutropenia occurred in 58% of patients treated with the combination of Idelalisib and rituximab or with an unapproved combination therapy. Blood counts are monitored at least every 2 weeks for the first 6 months of treatment and at least weekly in patients with neutrophil counts below 1.0 Gi/L. Idelalisib treatment is suspended until remission, and then treatment is resumed at a reduced dose.

Embryo-fetal toxicity

Based on its findings in animals and its mechanism of action, Idelalisib may cause fetal harm when administered to pregnant women, informing pregnant women of its potential risks to the fetus. Women of childbearing potential are advised to use effective contraception during treatment with Idelalisib and for 1 month after the last dose.