Oncology Overview: Idelalisib in Blood Cancers


Approved indications for idelalisib include relapsed chronic lymphocytic leukemia, small lymphocytic lymphoma, and follicular B-cell non-Hodgkin lymphoma.

Idelalisib (Zydelig) is a prescription oral tablet chemotherapy approved for 3 types of blood cancer. The FDA granted idelalisib accelerated approval on July 23, 2014.

Its indications include relapsed chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular B-cell non-Hodgkin lymphoma (FL). The rate of new CLL and SLL cases from 2014 to 2018 was 4.6 per 100,000 men and women per year and the death rate was 0.9 per 100,000 per year.

These cancers are treated with other chemotherapeutic regimens, such as R-CVP and R-CHOP. These regimens include the monoclonal antibody rituximab at a dose of 375 mg/m2 weekly.

Mechanism of Action

Idelalisib is a first in class Pl3K Delta inhibitor. PIK3CD is a gene that provides instructions for making the gene p110 delta, a subunit of an enzyme that turns on signaling pathways within in cells. PI3K-delta is found in white blood cells and causes them to grow and differentiate. In blood cancer, idelalisib inhibits unfettered cancer cell growth.

Idelalisib is available as 100 mg and 150 mg tablets, with a recommended dose of 150 mg BID. If severe adverse effects (AEs) occur, the dose is lowered to 100 mg BID.

In the treatment of both relapsed FL or relapsed SLL, eligible patients must have received at least 2 prior systemic therapies. In one study, the overall response rate was 54% for FL and 58% for SLL. Serious AEs were experienced by 50% of patients, including pneumonia, pyrexia, sepsis.

The most common AEs (incidence greater or equal to 30%) in patients treated with idelalisib in combination trials are diarrhea, pneumonia, pyrexia, fatigue, rash, cough, and nausea. Common laboratory abnormalities include neutropenia, ALT elevations, and AST elevations.

Warnings, Precautions, Patient Counseling Points

The most common AEs with idelalisib, which may affect 1 in 10 patients, are infections, with the most serious lung infections caused by Pneumocystis jirovecii (formerly called carinii). This infection requires treatment with trimethoprim/sulfamethoxazole (TMP/SXT) dosed at 4 to 5 mg/kg intravenous (IV) or orally 3 times a day for 14 to 21 days.

Pentamidine 4 mg IV once a day or clindamycin 300 mg to 900 mg IV every 6 to 8 hours with primaquine base 15 mg to 30 mg once a day are alternatives. Prophylaxis with TMP/SXT may be required for the duration of idelalisib treatment.

REMS Required

In 2018, the FDA required Gilead Sciences to publish REMS safety information for health care professionals and patients describing a boxed warning was for the risk of fatal and/or serious hepatotoxicity, fatal and/or serious and severe diarrhea or colitis, and fatal or serious intestinal perforation. This boxed warning reflected data from patients treated with idelalsib and rituximab or other unapproved combinations.

Avoid coadministration of strong CYP3A inducers and provide additional monitoring if alternative therapy is not available. Idelalisib also interacts with CYP3A substrates, which should be avoided.

About the Author

Charles E. Libby, RPh, MS, is a retired pharmacist who is enrolled in the University of Connecticut’s Medical Writing Certificate Program.


Sethi S. Pneumocystis jirovecii Pneumonia. Merck Manual Last full review/revision Dec 2020.

ZYDELIG REMS FACT Sheet 2018 Gilead Sciences. Accessed July 16, 2021. REMS_Factsheet_012018.pdf (zydeligrems.com)

Shah A, Mangaonkar A. Idelalisib: A novel pi3kδ inhibitor for chronic lymphocytic leukemia. Ann Pharmacother. 2015 Oct;49(10):1162-70. doi: 10.1177/1060028015594813. Epub

Miller BW, Przepiorka D, de Claro RA, et al. FDA approval: idelalisib monotherapy for the treatment of patients with follicular lymphoma and small lymphocytic lymphoma. Clin Cancer Res. 2015;21(7):1525-1529. doi:10.1158/1078-0432.CCR-14-2522

Bird ST, Tian F, Flowers N, et al. Idelalisib for treatment of relapsed follicular lymphoma and chronic lymphocytic leukemia: a comparison of treatment outcomes in clinical trial participants vs Medicare beneficiaries. JAMA Oncol. 2020 Feb 1;6(2):248-254. doi: 10.1001/jamaoncol.2019.3994.

Braga BP, Prieto-González S, Hernández-Rodríguez J. Pneumocystis jirovecii pneumonia prophylaxis in immunocompromised patients with systemic autoimmune diseases. Med Clin (Barc). 2019;152(12):502-507. doi: 10.1016/j.medcli.2019.01.010.

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