Effects of duvelisib: A Synthesis of Findings from 19 Studies

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Original Abstract of the Article

Major Research Findings

Duvelisib is a PI3K inhibitor that has shown promise in treating various types of cancers, particularly B-cell malignancies. 13 It works by inhibiting the PI3K pathway, which is crucial for cell growth, survival, and proliferation. 15 Studies have shown that duvelisib can effectively inhibit the growth of lymphoma cells, including those associated with Epstein-Barr virus. 2 Additionally, duvelisib has demonstrated a potential role in treating pulmonary fibrosis by inhibiting the PI3K/Akt/mTOR pathway. 10 Furthermore, duvelisib has been investigated for its ability to prevent the development of neuropathic pain in a model of paclitaxel-induced peripheral neuropathy, showing positive results. 16 However, it's important to note that duvelisib can also have significant side effects, particularly related to immune function. 8

Benefits and Risks

Benefits Summary

Duvelisib has shown potential as a treatment for a variety of cancers, including B-cell malignancies, lymphoma associated with Epstein-Barr virus, and pulmonary fibrosis. 2 10 13 It may also be effective in preventing neuropathic pain associated with chemotherapy. 16

Risks Summary

Duvelisib can cause adverse effects, particularly those related to immune function. 8 It can potentially lead to T-cell deficiencies and an increased risk of infections. 8 Furthermore, it has been associated with autoimmune toxicity, such as colitis. 6

Comparison Between Studies

Similarities Between Studies

Several studies have highlighted the effectiveness of duvelisib in treating various cancers, including B-cell malignancies and lymphoma associated with Epstein-Barr virus. 13 2 These studies also consistently emphasize the importance of closely monitoring patients for potential adverse effects, especially those related to immune function. 8

Differences Between Studies

While the studies consistently show duvelisib's effectiveness in various cancer types, the specific details of its efficacy and the incidence of side effects can vary depending on the specific type of cancer, patient characteristics, and the research methodology used. 13 2 Some studies have reported more pronounced positive effects, while others have observed more moderate results. 13 2 Similarly, the prevalence and severity of side effects can vary between studies. 8

Consistency and Inconsistencies in Findings

While duvelisib shows promise in treating cancers, the results regarding its effectiveness and safety are not entirely consistent across all studies. Some studies have reported significant benefits, while others have highlighted potential limitations and risks associated with its use. 13 2 More research is needed to clarify the precise efficacy and safety profile of duvelisib for various types of cancer and to identify factors that may influence its effectiveness and the incidence of side effects.

Considerations for Real-Life Applications

Duvelisib may be an effective treatment option for certain types of cancer, but it is crucial to weigh its potential benefits against the associated risks. 11 Patients should discuss their individual medical history, treatment options, and the potential risks and benefits with their healthcare provider to determine whether duvelisib is an appropriate choice for them. 11 Close monitoring for side effects is essential throughout the course of treatment.

Limitations of Current Research

The research on duvelisib is ongoing, and further investigation is required to fully understand its long-term effects and to determine its optimal application in various clinical settings. 13 More research is also needed to develop strategies for minimizing side effects and improving the overall safety profile of duvelisib. 11

Future Research Directions

Future research on duvelisib should focus on clarifying its long-term effects, optimizing its use in various cancer types, and developing strategies for minimizing its side effects. 13 11 Investigating the interplay between duvelisib and other cancer therapies, including immune checkpoint inhibitors, is also important to explore potential synergistic effects and develop more personalized treatment approaches. 13

Conclusion

Duvelisib holds promise as a treatment option for certain types of cancer, but more research is needed to fully understand its efficacy and safety. 13 While duvelisib may be effective in treating some cancers, it is important to weigh the potential benefits against the associated risks. 11 Patients should discuss their treatment options with their healthcare provider to determine if duvelisib is right for them. 11

Literature analysis of 19 papers
Positive Content
16
Neutral Content
2
Negative Content
1
Article Type
1
0
0
8
19
1.

Effect of dutasteride on intraprostatic androgen levels in men with benign prostatic hyperplasia or prostate cancer.

Author: RittmasterRoger, HahnRobert G, RayPaul, ShannonJennifer B, WurzelRafael

Suppresses DHT

Dutasteride, a medication used to treat enlarged prostates, reduced levels of dihydrotestosterone (DHT) in the prostate and serum.

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.

Language : English

2.

Antitumor effects of duvelisib on Epstein-Barr virus-associated lymphoma cells.

Author: KawadaJun-Ichi, AndoShotaro, ToriiYuka, WatanabeTakahiro, SatoYoshitaka, ItoYoshinori, KimuraHiroshi

Lymphoma treatment

This study investigated the effects of duvelisib, a dual inhibitor of PI3Kγ and PI3Kδ, on EBV-associated lymphoma cell lines. Duvelisib inhibited cellular growth and induced apoptosis in EBV-positive and -negative B cell lines, but not in T cell lines. The study also found that duvelisib suppressed the lytic cycle of EBV, suggesting that it may have therapeutic potential for the treatment of EBV-associated B cell lymphomas.

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

4.

Metabolic and toxicological considerations for phosphoinositide 3-kinase delta inhibitors in the treatment of chronic lymphocytic leukemia.

Author: WitkowskaMagdalena, MajchrzakAgata, RobakPaweł, Wolska-WasherAnna, RobakTadeusz

Effective B-cell lymphoma treatment

PI3Kδ inhibitors, such as idelalisib, are new drugs that are used to treat B-cell malignancies. These drugs work by blocking a specific enzyme called PI3Kδ. Idelalisib is the first PI3Kδ inhibitor that has been approved for use in patients with B-cell lymphoid malignancies.

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.

Current Treatment Options in Relapsed and Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: a Review.

Author: IslamPrioty

CLL treatment

This review discusses the current treatment landscape for relapsed and refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL), outlining different therapeutic approaches based on prior therapies and highlighting the importance of clinical trial enrollment for patients with complex disease.

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

6.

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

7.

PI3k Inhibitors in NHL and CLL: An Unfulfilled Promise.

Author: Bou ZeidNaji, YazbeckVictor

CLL treatment
iNHL treatment
Adverse effects
Decreased survival

This mini-review revisits the clinical successes, the failures, and the promising aspect of PI3K inhibitors in the treatment of hematologic malignancies. It also presents possible ways that could benefit its successful development.

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

9.

Circulating Th17 T cells at treatment onset predict autoimmune toxicity of PI3Kδ inhibitors.

Author: GadiDeepti, MartindaleStephen P, ChiuPui Yan, KhalsaJasneet, ChenPei-Hsuan, FernandesStacey M, WangZixu, TyekuchevaSvitlana, MachadoJohn-Hanson, FisherDavid C, ArmandPhilippe, DavidsMatthew S, RodigScott, SherryBarbara, BrownJennifer R

B cell malignancy therapy
PI3K inhibitor toxicity
autoimmune toxicity

This study investigates the in vitro effects of PI3Kδ inhibitors (idelalisib and duvelisib) on T cell differentiation and proliferation. The study found that these inhibitors can promote Th17 differentiation while inhibiting Treg differentiation, potentially contributing to autoimmune toxicity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Duvelisib attenuates bleomycin-induced pulmonary fibrosis via inhibiting the PI3K/Akt/mTOR signalling pathway.

Author: LiXiaohe, MaXiaoyang, MiaoYang, ZhangJianwei, XiBuri, LiWenqi, ZhangQianyi, ChenLi, YangYue, LiHongli, WeiLuqing, ZhouHonggang, YangCheng

Autophagy inhibition improvement
Fibroblast activation suppression
Pulmonary fibrosis alleviation

This study investigated the effects of Duvelisib, a PI3K inhibitor, on pulmonary fibrosis using a mouse model. Duvelisib alleviated bleomycin-induced collagen deposition and improved pulmonary function. This suggests that Duvelisib may offer a potential therapeutic approach for the treatment of pulmonary fibrosis.

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

12.

Current status of phosphoinotiside-3 kinase inhibitors in blood cancers.

Author: ShouseGeoffrey, DanilovaOlga V, DanilovAlexey V

CLL treatment
NHL treatment

PI3K inhibitors have been approved by the FDA for the treatment of NHL and CLL and are proving to be effective treatments, but they also present unique challenges in routine practice.

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.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

PI3K Inhibitors for the Treatment of Chronic Lymphocytic Leukemia: Current Status and Future Perspectives.

Author: HusIwona, PułaBartosz, RobakTadeusz

CLL treatment
autoimmune-mediated pneumonitis
colitis
infections

Phosphoinositide 3-kinase delta (PI3Kδ) inhibitors have shown promise in treating chronic lymphocytic leukemia (CLL). Idelalisib, the first PI3Kδ inhibitor, had significant side effects. Duvelisib and umbralisib, newer PI3Kδ inhibitors, have shown improved safety profiles.

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.

The evidence to date on umbralisib for the treatment of refractory marginal zone lymphoma and follicular lymphoma.

Author: SchweitzerJanelle, HoffmanMeghan, GrafSolomon A

Follicular lymphoma treatment
PI3K inhibitor efficacy
Drug safety concerns
Toxicity

Umbralisib, a PI3K inhibitor, is a promising treatment for relapsed/refractory indolent B-cell lymphoma (iB-NHL) with potential improved tolerability.

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

15.

PI3Kδ/γ inhibition promotes human CART cell epigenetic and metabolic reprogramming to enhance antitumor cytotoxicity.

Author: FunkChristopher Ronald, WangShuhua, ChenKevin Z, WallerAlexandra, SharmaAditi, EdgarClaudia L, GuptaVikas A, ChandrakasanShanmuganathan, ZoineJaquelyn T, FedanovAndrew, RaikarSunil S, KoffJean L, FlowersChristopher R, ComaSilvia, PachterJonathan A, RavindranathanSruthi, SpencerH Trent, ShanmugamMala, WallerEdmund K

CART cell expansion
CLL elimination
Survival improvement

This study investigated the effects of inhibiting PI3Kδ and PI3Kγ isoforms during the manufacture of chimeric antigen receptor T (CART) cells from patients with chronic lymphocytic leukemia (CLL).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

The TKI Era in Chronic Leukemias.

Author: De NovellisDanilo, CacaceFabiana, CaprioliValeria, WierdaWilliam G, MahadeoKris M, TambaroFrancesco Paolo

CLL remission
CML remission
Improved outcomes
Side effects

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). TKIs like imatinib, dasatinib, and nilotinib target BCR-ABL1 in CML, while BTK inhibitors like ibrutinib and acalabrutinib target the B-cell receptor signaling pathway in CLL. These agents have improved outcomes for patients with these hematologic malignancies but may have associated side effects.

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

18.

A T cell inflammatory phenotype is associated with autoimmune toxicity of the PI3K inhibitor duvelisib in chronic lymphocytic leukemia.

Author: GadiDeepti, GriffithAlec, TyekuchevaSvitlana, WangZixu, RaiVanessa, VartanovAlexander, ThrashEmily, FernandesStacey M, LehmbergTimothy Z, LeeBrandon, MartindaleStephen P, MachadoJohn-Hanson, OdejideOreofe, ArmandPhilippe, FisherDavid C, ArnasonJon, DavidsMatthew S, LedererJames A, BrownJennifer R

CLL treatment
Autoimmune toxicity

Duvelisib, a PI3Kδγ inhibitor, is used to treat chronic lymphocytic leukemia (CLL). Approximately one-third of patients experience autoimmune toxicity. The study found that an increase in activated CD8 T cells with activation of Th17 T cells, in the context of lower baseline Tregs and greater CLL resistance to duvelisib, is associated with duvelisib-related autoimmune toxicity.

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.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

19.

Protein Kinase CK1α Sustains B-Cell Receptor Signaling in Mantle Cell Lymphoma.

Author: ManniSabrina, FregnaniAnna, Quotti TubiLaura, SpinelloZaira, CarraroMarco, ScapinelloGreta, VisentinAndrea, BarilàGregorio, PizziMarco, Dei TosAngelo Paolo, VianelloFabrizio, ZambelloRenato, GurrieriCarmela, SemenzatoGianpietro, TrentinLivio, PiazzaFrancesco

MCL treatment

This study found that CK1α sustains mantle cell lymphoma (MCL) growth through the regulation of BCR-linked survival signaling cascades and protects from Ibrutinib/Duvelisib-induced apoptosis. Thus, CK1α could be considered as a rational molecular target for the treatment of MCL, in association with novel agents.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

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