Side Effects of idelalisib: A Synthesis of Findings from 14 Studies

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Original Abstract of the Article

Key Research Findings

Idelalisib is a drug approved for the treatment of relapsed chronic lymphocytic leukemia (CLL) and follicular B-cell lymphoma. 2 It is a potent and selective inhibitor of phosphatidylinositol 3-kinase-δ (PI3K-δ), which is primarily expressed in B-cells and effectively prevents proliferation in malignant B-cells. 2 Idelalisib has been reported to cause a variety of side effects, including gastrointestinal, liver, lung, and immune system problems. 13 , 12 , 10 , 5 The most common side effect is gastrointestinal toxicity, including diarrhea and colitis, which is thought to occur because Idelalisib inhibits the function of immune cells in the digestive tract. 3 , 13 Liver problems, such as elevated liver enzyme levels and hepatitis, can also occur due to Idelalisib's direct toxicity to liver cells. 13 , 4 Idelalisib can also cause lung problems, such as pneumonia and interstitial pneumonia, due to its inhibition of immune cells in the lungs. 12 Idelalisib can suppress the activity of immune cells, leading to an increased risk of infections and the potential development of autoimmune diseases. 13 , 8 It has been reported that Idelalisib inhibits the function of Treg cells, which are immune-suppressing cells that help prevent autoimmune diseases. 8

Reasons for Side Effects

Idelalisib inhibits the activity of PI3K-δ, which plays a role in a variety of cellular functions, such as cell proliferation, survival, and immune response. 9 Therefore, inhibiting the activity of PI3K-δ is believed to cause various side effects.

Common Side Effects

Gastrointestinal

The most common side effect of Idelalisib administration is gastrointestinal toxicity, including diarrhea and colitis. 3 , 13 These are believed to occur because Idelalisib inhibits the function of immune cells in the digestive tract. 13 In severe cases, complications such as colitis and gastrointestinal perforation can occur. 3

Liver

Idelalisib can cause liver problems, such as elevated liver enzyme levels and hepatitis, due to its direct toxicity to liver cells. 13 , 4

Lungs

Idelalisib can cause lung problems, such as pneumonia and interstitial pneumonia, due to its inhibition of immune cells in the lungs. 12

Immune System

Idelalisib can suppress the activity of immune cells, leading to an increased risk of infections and the potential development of autoimmune diseases. 13 , 8 It has been reported that Idelalisib inhibits the function of Treg cells, which are immune-suppressing cells that help prevent autoimmune diseases. 8

Countermeasures for Side Effects

Gastrointestinal

To prevent gastrointestinal side effects, it is essential to assess the condition of the digestive tract before administering Idelalisib and administer gastrointestinal protectants if necessary. 13 If symptoms such as diarrhea appear, it is important to provide fluid replacement and administer antidiarrheal medications as needed. 3 In severe cases, discontinuation of Idelalisib administration may be necessary. 3

Liver

To prevent liver damage, it is essential to assess liver function before administering Idelalisib and perform regular liver function tests if necessary. 13 If elevated liver enzyme levels occur, it may be necessary to reduce the dosage of Idelalisib or discontinue administration. 4

Lungs

To prevent lung damage, it is essential to assess the condition of the lungs before administering Idelalisib and perform regular pulmonary function tests if necessary. 12 If lung damage is suspected, medications such as steroids may need to be administered. 12

Immune System

To reduce the risk of infections, it is essential to provide vaccinations before administering Idelalisib and prophylactically administer antibiotics if necessary. 13 If symptoms of infection appear, it is essential to provide prompt and appropriate treatment. 13 To suppress the risk of developing autoimmune diseases, it is essential to confirm the history of autoimmune diseases before administering Idelalisib. 8 If symptoms of autoimmune disease appear, it is essential to provide prompt and appropriate treatment.

Comparison Between Studies

Commonalities Between Studies

Multiple studies have reported that Idelalisib administration can cause side effects affecting the gastrointestinal tract, liver, lungs, and immune system. 3 , 13 , 12 , 8

Differences Between Studies

There is variability in the frequency and severity of side effects reported in each study. 3 , 13 , 12 , 8 This is believed to be influenced by differences in the patient populations studied, Idelalisib dosage, concomitant medications, and other factors.

Points to Note Regarding Real-Life Applications

Idelalisib is an effective drug for treating B-cell malignancies, but it can cause various side effects. 2 When considering administering Idelalisib, it is essential to carefully evaluate the risks and benefits of the side effects and make treatment decisions after discussing them thoroughly with the patient. 11 It is particularly important to exercise caution in elderly patients and those with comorbidities, as they may have a higher risk of side effects. 4 Additionally, regular physical examinations and blood tests must be performed during Idelalisib administration. 13 Consult a doctor immediately if any side effects occur.

Limitations of Current Research

Research on the side effects of Idelalisib is still insufficient. 3 In particular, further research is necessary regarding long-term side effects and the impact of Idelalisib administration on genes. 10 It is also crucial to thoroughly consider the side effects of co-administering Idelalisib with other drugs. 11 Furthermore, it is important to elucidate the individual differences in side effects caused by Idelalisib administration. 8

Future Research Directions

The development of new treatments and preventive measures to reduce the side effects of Idelalisib is needed. 13 Elucidating the mechanisms underlying the side effects caused by Idelalisib administration is expected to lead to more effective prevention and treatment of these side effects. 5 Developing biomarkers to detect side effects caused by Idelalisib administration at an early stage is also crucial. 11

Conclusion

Idelalisib is an effective drug for treating B-cell malignancies, but it can cause various side effects. 13 When considering administering Idelalisib, it is essential to carefully evaluate the risks and benefits of the side effects and make treatment decisions after discussing them thoroughly with the patient. 11 Further research on the side effects of Idelalisib is needed. 3

Literature analysis of 14 papers
Positive Content
13
Neutral Content
1
Negative Content
0
Article Type
1
0
0
7
14
1.

Specific side effects of long-term imipramine management of panic disorder.

Author: MavissakalianMatig, PerelJames, GuoShenyang

Panic disorder treatment
Dry mouth
Sexual dysfunction
Sweating
Tachycardia
Weight gain

Imipramine, an antidepressant, is effective for panic disorder, but can cause side effects like dry mouth, sweating, and weight gain.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

2.

Idelalisib may have the potential to increase radiotherapy side effects.

Author: GrycThomas, PutzFlorian, GoerigNicole, ZieglerSonia, FietkauRainer, DistelLuitpold V, SchusterBarbara

Cancer treatment

This study focuses on idelalisib, a potent and selective phosphatidylinositol 3-kinase-δ (PI3K-δ) inhibitor, and its application in treating relapsed chronic lymphocytic leukemia, follicular B-cell non-Hodgkin's lymphoma, and small lymphocytic lymphoma. The study highlights idelalisib's selective targeting of PI3K-δ, which is primarily expressed in B-cells, and its potential for effectively inhibiting proliferation in malignant B-cells.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

3.

Management of Gastro-Intestinal Toxicity of the Pi3 Kinase Inhibitor: Optimizing Future Dosing Strategies.

Author: BrealClaire, BeuvonFrederic, de Witasse-ThezyThibault, DermineSolene, Franchi-RezguiPatricia, Deau-FisherBenedicte, WillemsLise, GrignanoEric, ContejeanAdrien, BouscaryDidier, FaillieJean Luc, TreluyerJean-Marc, GuerinCorinne, ChouchanaLaurent, VignonMarguerite

Cancer treatment
Colitis

This review examines the use of phosphatidylinositol 3-kinase (PI3K) inhibitors for hematological malignancies, focusing on the incidence and toxicity of PI3K inhibitor-induced colitis. It discusses the side effects reported in clinical trials and pharmacovigilance data, and provides real-world experience in managing idelalisib-induced colitis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

4.

Hepatotoxicity of Small Molecule Protein Kinase Inhibitors for Cancer.

Author: ViganòMauro, La MiliaMarta, GrassiniMaria Vittoria, PuglieseNicola, De GiorgioMassimo, FagiuoliStefano

Cancer treatment
Hepatotoxicity

Hepatotoxicity is a significant concern with protein kinase inhibitors (PKIs), used to treat cancer. This review discusses the risk and management of hepatotoxicity associated with approved PKIs, emphasizing the need for careful patient evaluation and monitoring.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

5.

Immune modulatory effects of Idelalisib in stromal cells of chronic lymphocytic leukemia.

Author: HandlSarah, von HeydebrandFranziska, VoelklSimon, OostendorpRobert A J, WilkeJochen, KremerAnita N, MackensenAndreas, Lutzny-GeierGloria

Improved therapies
Side effects

Idelalisib, a PI3K inhibitor, activates the NF-κB pathway in stromal cells in contact with CLL cells, potentially contributing to patient side effects. The study also investigated a 3D-stroma/leukemia model, which could improve therapeutic strategies, especially for minimal-residual disease.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

Current Treatment of Refractory/Relapsed Chronic Lymphocytic Leukemia: A Focus on Novel Drugs.

Author: SmolewskiPiotr, RobakTadeusz

CLL treatment
Drug toxicity

Treatment strategies for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) include Bruton tyrosine kinase inhibitors, PI3K inhibitors, B-cell lymphoma 2 inhibitors, and novel CD20 monoclonal antibodies. Treatment selection depends on various factors, including prior therapy response, side effects, and comorbidities.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

8.

Loss of Phosphatidylinositol 3-Kinase Activity in Regulatory T Cells Leads to Neuronal Inflammation.

Author: StarkAnne-Katrien, DavenportElizabeth C M, PattonDaniel T, ScudamoreCheryl L, VanhaesebroeckBart, VeldhoenMarc, GardenOliver A, OkkenhaugKlaus

CNS inflammation protection
Treg cell function
Immune dysregulation
Treg cell loss

PI3Kδ is crucial for Treg cell function, a type of immune cell that helps prevent autoimmune diseases. Blocking PI3Kδ can treat some cancers, but it can also cause immune problems. This study found that blocking both PI3Kα and PI3Kδ together worsened autoimmune disease in mice, highlighting the importance of PI3K signaling in immune regulation.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Isoform-Selective PI3K Inhibitors for Various Diseases.

Author: BheemanaboinaRammohan R Y

Cancer treatment
Off-target effects

Isoform-selective PI3K inhibitors have emerged as promising therapeutic agents for cancer and other diseases. These inhibitors are crucial for understanding the unique functions of each PI3K isoform and its potential therapeutic applications.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

11.

Author: TroussardXavier

CLL treatment
Side effects

This paper reviews the treatment of chronic lymphocytic leukemia (CLL), focusing on first-line therapy and treatment of relapsed or refractory (R/R) CLL. It discusses the use of immunochemotherapy, including anti-CD20 monoclonal antibodies, and BCR inhibitors.

English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : French

13.

Management of adverse events associated with idelalisib treatment in chronic lymphocytic leukemia and follicular lymphoma: A multidisciplinary position paper.

Author: CuneoAntonio, BarosiGiovanni, DanesiRomano, FagiuoliStefano, GhiaPaolo, MarzanoAlfredo, MontilloMarco, PolettiVenerino, VialePierluigi, ZinzaniPier Luigi

CLL treatment
FL treatment
Idelalisib side effects

A consensus document provides practical recommendations for managing side effects during idelalisib therapy for chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

14.

Balancing efficacy and toxicity of targeted agents currently used for the treatment of patients with chronic lymphocytic leukemia.

Author: MauroFrancesca R, CaputoMaria D, RosatiSerena, PepeSara, De BenedittisDaniela, De LucaMaria L, FoàRobin

CLL treatment
Chemo-free options
Targeted agents
Unique side effects

This review discusses the use of small molecules to treat chronic lymphocytic leukemia (CLL). While these drugs offer new chemo-free options, they can also cause unique side effects. The review highlights the importance of awareness and management of these toxicities for successful treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

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