Side Effects of ixazomib: A Synthesis of Findings from 22 Studies

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Original Abstract of the Article

Major Research Findings

Ixazomib is an oral proteasome inhibitor used to treat multiple myeloma. 14 . Ixazomib has been shown to be effective in treating multiple myeloma. 12 . Ixazomib, in combination with lenalidomide and dexamethasone, has shown to slow the progression of multiple myeloma. 12 . Ixazomib may help improve patients' QOL because it has fewer side effects than other proteasome inhibitors and can be administered orally. 14 .

Reasons for Side Effects

Ixazomib is thought to cause various side effects by inhibiting the proteasome and disrupting the normal function of cells. 11 . Specifically, the proteasome is responsible for breaking down unnecessary proteins in the cell, but when ixazomib inhibits the proteasome, unnecessary proteins accumulate, disrupting cellular function. 11 . Ixazomib may also cause side effects by activating the cell's stress response system. 11 .

Common Side Effects

Thrombocytopenia

Thrombocytopenia has been reported as a side effect of ixazomib. 14 , 12 . Platelets are involved in blood clotting, and thrombocytopenia increases the risk of bleeding. 12 .

Nausea and Vomiting

Nausea and vomiting have been reported as side effects of ixazomib. 14 , 12 . Nausea and vomiting may be caused by digestive system dysfunction or reaction to the drug. 12 .

Diarrhea and Constipation

Diarrhea and constipation have been reported as side effects of ixazomib. 14 , 12 . Diarrhea and constipation may be caused by digestive system dysfunction or reaction to the drug. 12 .

Rash

Rash has been reported as a side effect of ixazomib. 14 . Rash may be caused by an allergic reaction or a reaction to the drug. 14 .

Peripheral Neuropathy

Peripheral neuropathy has been reported as a side effect of ixazomib. 14 . Peripheral neuropathy is caused by nerve damage and results in symptoms such as numbness and pain in the hands and feet. 14 . Ixazomib has been reported to have a lower incidence of peripheral neuropathy compared to other proteasome inhibitors. 14 .

Peripheral Edema

Peripheral edema has been reported as a side effect of ixazomib. 12 . Peripheral edema is a condition where fluid accumulates in the hands and feet. 12 .

Back Pain

Back pain has been reported as a side effect of ixazomib. 12 . Back pain may be caused by a reaction to the drug or by the impact of multiple myeloma on bones. 12 .

Side Effect Management

Thrombocytopenia

Management of thrombocytopenia includes platelet transfusions. 12 . If the risk of bleeding is high, ixazomib administration may be discontinued. 12 .

Nausea and Vomiting

Management of nausea and vomiting includes administration of antiemetics. 12 . Dietary changes and hydration can also be helpful. 12 .

Diarrhea and Constipation

Management of diarrhea and constipation includes administration of antidiarrheal agents or laxatives, respectively. 12 . Dietary changes and hydration can also be helpful. 12 .

Rash

Management of rash includes administration of topical steroids. 14 . In severe cases, ixazomib administration may be discontinued. 14 .

Peripheral Neuropathy

Management of peripheral neuropathy includes administration of medications to alleviate the symptoms of neuropathy. 14 . Keeping hands and feet warm and massage can also be helpful to reduce stress on nerves. 14 .

Peripheral Edema

Management of peripheral edema includes administration of diuretics. 12 . Elevating the legs can also be helpful. 12 .

Back Pain

Management of back pain includes administration of analgesics. 12 . Treatment for osteoporosis may also be provided to reduce the impact on bones. 12 .

Comparison between Studies

Commonalities

Ixazomib has been shown to be effective in treating multiple myeloma. 12 , 14 . Ixazomib has been reported to have a lower incidence of peripheral neuropathy compared to other proteasome inhibitors. 14 . Ixazomib, being orally available, can help improve patients' QOL. 14 .

Differences

The frequency and severity of ixazomib's side effects vary depending on the study. 14 , 12 .

Notes on Real-World Application

Ixazomib is an effective drug for treating multiple myeloma, but it has the potential to cause various side effects. 14 , 12 . When using ixazomib, it is important to follow your doctor's instructions and be aware of potential side effects. 14 , 12 . Also, ixazomib may interact with other medications, so consult your doctor if you are taking other medications. 14 , 12 .

Current Research Limitations

The long-term safety of ixazomib is not fully understood yet. 14 . Furthermore, more research is needed to understand the mechanisms by which ixazomib causes side effects. 11 .

Future Research Directions

Research is needed to understand the long-term safety of ixazomib and the mechanisms by which it causes side effects. 14 , 11 . Research is also needed to improve the effectiveness of ixazomib and reduce its side effects. 14 , 11 .

Conclusion

Ixazomib is an effective drug for treating multiple myeloma, but it has the potential to cause various side effects. 14 , 12 . When using ixazomib, it is important to follow your doctor's instructions and be aware of potential side effects. 14 , 12 .

Literature analysis of 22 papers
Positive Content
21
Neutral Content
0
Negative Content
1
Article Type
1
0
0
15
21
1.

Cutaneous Adverse Events of Targeted Therapies for Hematolymphoid Malignancies.

Author: RansohoffJulia D, KwongBernice Y

Liquid tumor treatment
Cutaneous adverse events

This article discusses the cutaneous adverse events (AEs) associated with targeted therapies for hematologic and lymphoid malignancies. It provides a comprehensive review of the AE profiles of various targeted agents, emphasizing the importance of early diagnosis and management of skin toxicities to minimize disruptions to care and optimize patient outcomes.

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

2.

Cardiovascular Complications of Multiple Myeloma Treatment: Evaluation, Management, and Prevention.

Author: LeeDae Hyun, FradleyMichael G

Multiple myeloma treatment
Cardiotoxicity

Multiple myeloma treatment regimens often include proteasome inhibitors, immunomodulatory drugs, and steroids, all of which can have adverse effects on the heart. This article discusses the cardiovascular complications associated with these treatment modalities and methods to mitigate them.

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

3.

Cardiovascular adverse events in multiple myeloma patients.

Author: HeckmannMarkus B, DoroudgarShirin, KatusHugo A, LehmannLorenz H

Efficient treatment
Improved survival
Cardiovascular adverse events

This article reviews the clinical and preclinical data on approved proteasome inhibitors, such as bortezomib, carfilzomib, and ixazomib, used to treat multiple myeloma. The review focuses on the underlying pathomechanisms related to cardiovascular adverse events observed in clinical trials, highlighting the need for further research to understand and manage these 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

5.

Next-generation proteasome inhibitor MLN9708 sensitizes breast cancer cells to doxorubicin-induced apoptosis.

Author: WangHao, YuYang, JiangZheng, CaoWen-Ming, WangZhenyu, DouJun, ZhaoYanling, CuiYunfu, ZhangHong

MLN9708 for breast cancer
Doxorubicin side effects

MLN9708, a proteasome inhibitor, was found to have antitumor effects in breast cancer cells and may enhance the efficacy of doxorubicin treatment.

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

6.

Safety of proteasome inhibitors for treatment of multiple myeloma.

Author: SchlaferDanielle, ShahKatherine S, PanjicElyse Hall, LonialSagar

Multiple myeloma treatment
Peripheral neuropathy
Resistance development

This review focuses on the safety data from clinical trials for the three approved proteasome inhibitors (PIs) and how to manage adverse effects. The review also includes a summary of efficacy data from select clinical trials.

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.

Non-Hematologic Toxicity of Bortezomib in Multiple Myeloma: The Neuromuscular and Cardiovascular Adverse Effects.

Author: PancheriElia, GuglielmiValeria, WilczynskiGrzegorz M, MalatestaManuela, ToninPaola, TomelleriGiuliano, NowisDominika, VattemiGaetano

MM treatment
Cardiovascular toxicity
Neuromuscular toxicity

The study reviews the neuromuscular and cardiovascular side effects of bortezomib, a proteasome inhibitor used in the treatment of multiple myeloma (MM), focusing on the molecular mechanisms underlying its toxicity.

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

8.

Optimizing current and emerging therapies in multiple myeloma: a guide for the hematologist.

Author: RazaShahzad, SafyanRachael A, RosenbaumEvan, BowmanAlex S, LentzschSuzanne

Improved overall survival
Improved response rates

This review outlines the current therapeutic approach to the management of multiple myeloma (MM). It highlights the advancements in treatment options, including proteasome inhibitors and immunomodulatory drugs, and emphasizes the importance of risk stratification, management of comorbidities, and treatment 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

9.

Oral Proteasome Inhibitor Ixazomib for Switch-Maintenance Prophylaxis of Recurrent or Late Acute and Chronic Graft-versus-Host Disease after Day 100 in Allogeneic Stem Cell Transplantation.

Author: RodriguezNatasia, LeeJasme, FlynnLisa, MurrayFiona, DevlinSean M, SotoCristina, ChoChristina, DahiParastoo, GiraltSergio, PeralesMiguel-Angel, SauterCraig, PonceDoris M

GVHD prophylaxis
GVT effect
GVHD

Ixazomib, an oral proteasome inhibitor, is a promising agent for switch-maintenance GVHD prophylaxis after stem cell transplantation. A pilot study showed that ixazomib facilitated CNI taper without increasing GVHD frequency and severity while maintaining graft-versus-tumor effect.

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

10.

A Rare Case of Ixazomib-Induced Cutaneous Necrotizing Vasculitis in a Patient with Relapsed Myeloma.

Author: KatzHeather, ShenoudaMina, DahshanDeena, SonnierGeorge, LebowiczYehuda

Myeloma treatment
Cutaneous necrotizing vasculitis

This case report describes a 74-year-old man with relapsed multiple myeloma who developed cutaneous necrotizing vasculitis after starting ixazomib.

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.

Language : English

11.

Molecular Cardiotoxic Effects of Proteasome Inhibitors Carfilzomib and Ixazomib and Their Combination with Dexamethasone Involve Mitochondrial Dysregulation.

Author: JannuzziAyse Tarbin, KorkmazNalan Sümeyra, Gunaydin AkyildizAysenur, Arslan EseryelSema, Karademir YilmazBetul, AlpertungaBuket

Cancer therapy
Cardiotoxicity reduction
Cardiotoxicity
Mitochondrial dysfunction

Proteasome inhibitors are an important class of drugs used in cancer treatment, but they can cause cardiotoxicity. This study investigated the cardiotoxic effects of carfilzomib (CFZ) and ixazomib (IXZ) in a cardiomyocyte model, finding that both drugs caused stress and mitochondrial dysfunction, potentially contributing to their cardiotoxic effects.

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.

Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma.

Author: KumarShaji, MoreauPhilippe, HariParameswaran, MateosMaria-Victoria, LudwigHeinz, ShustikChaim, MassziTamas, SpencerAndrew, HájekRoman, RomerilKenneth, AviviIrit, LiberatiAnna M, MinnemaMonique C, EinseleHermann, LonialSagar, BergDeborah, LinJianchang, GuptaNeeraj, EsseltineDixie-Lee, RichardsonPaul G

Multiple myeloma treatment
Back pain
Constipation
Diarrhea
Nausea
Peripheral edema
Peripheral neuropathy
Rash
Thrombocytopenia
Vomiting

Ixazomib, an oral proteasome inhibitor, is approved for the treatment of patients with multiple myeloma who have received at least one prior therapy. A clinical trial showed that ixazomib significantly improved progression-free survival compared to placebo. Common side effects included thrombocytopenia, nausea, vomiting, diarrhea, constipation, rash, peripheral neuropathy, peripheral edema, and back pain.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

13.

An analysis of the safety profile of proteasome inhibitors for treating various cancers.

Author: WangHui, GuanFangxia, ChenDi, DouQing Ping, YangHuanjie

Cancer therapy
Severe toxicities

Bortezomib is a proteasome inhibitor used to treat multiple myeloma (MM). Second-generation proteasome inhibitors, such as carfilzomib, ixazomib, oprozomib, and marizomib, have been developed to improve safety and efficacy.

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

14.

Safety of ixazomib for the treatment of multiple myeloma.

Author: BonnetAntoine, MoreauPhilippe

MM treatment
Oral administration
Cutaneous events
Digestive events
Hematological events

Ixazomib is the first oral proteasome inhibitor (PI) approved for the treatment of multiple myeloma (MM). This study reviews the preclinical and clinical evidence for ixazomib, highlighting its safety profile, efficacy, and potential role in long-term treatment strategies.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
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.

Soluble and Cell-Cell-Mediated Drivers of Proteasome Inhibitor Resistance in Multiple Myeloma.

Author: FarrellMariah L, ReaganMichaela R

Multiple myeloma treatment
PI resistance

This review discusses the mechanisms of proteasome inhibitor (PI) resistance in myeloma cells, focusing on non-autonomous (microenvironment dependent) mechanisms. The authors emphasize the importance of understanding these mechanisms to develop better strategies to overcome PI resistance and design more effective combination therapies.

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

16.

Proteasome inhibitor-induced gastrointestinal toxicity.

Author: StansboroughRomany L, GibsonRachel J

Gastrointestinal toxicity

Gastrointestinal toxicities are common side effects of proteasome inhibitors, with bortezomib causing the most severe 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.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

An evidence-based review of ixazomib citrate and its potential in the treatment of newly diagnosed multiple myeloma.

Author: OffidaniMassimo, CorvattaLaura, CaraffaPatrizia, GentiliSilvia, MaracciLaura, LeoniPietro

Improved response rate
Multiple myeloma treatment
Reduced bone loss
Diarrhea
Fatigue
Nausea
Rash
Thrombocytopenia
Vomiting

Proteasome inhibition is a key therapeutic target for multiple myeloma. Ixazomib, an oral proteasome inhibitor, has shown similar efficacy to bortezomib in controlling myeloma growth and preventing bone loss. Clinical trials suggest its effectiveness as a single agent and in combination with other medications.

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.

Targeting Ubiquitin-Proteasome System With Copper Complexes for Cancer Therapy.

Author: ChenXin, DouQ Ping, LiuJinbao, TangDaolin

Cancer treatment
Drug resistance
Drug-drug interactions
Side effects

This review summarizes the functions and applications of copper complexes as inhibitors of the ubiquitin-proteasome system (UPS) in cancer treatment. Copper complexes can inhibit key components of the UPS, suggesting their potential as novel anticancer agents.

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

19.

The evolving role of maintenance therapy following autologous stem cell transplantation in multiple myeloma.

Author: MerzAlmuth Maria Anni, MerzMaximilian, HillengassJens, HolsteinSarah A, McCarthyPhilip

Myeloma survival
Secondary malignancies
Side effects

This review explores the role of different maintenance strategies after autologous stem cell transplantation for newly diagnosed myeloma. It highlights the benefits of lenalidomide maintenance in prolonging progression-free and overall survival, but also acknowledges the potential side effects and discusses future research directions.

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

20.

Proteasome inhibitors for the treatment of multiple myeloma.

Author: ScalzulliEmilia, GrammaticoSara, VozellaFederico, PetrucciMaria Teresa

MM management
PI treatment

This study reviews the use of proteasome inhibitors (PIs) in the management of Multiple Myeloma (MM), including bortezomib, carfilzomib, and ixazomib.

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

21.

26S Proteasome Non-ATPase Regulatory Subunits 1 (PSMD1) and 3 (PSMD3) as Putative Targets for Cancer Prognosis and Therapy.

Author: RubioAndres J, Bencomo-AlvarezAlfonso E, YoungJames E, VelazquezVanessa V, LaraJoshua J, GonzalezMayra A, EiringAnna M

Cancer treatment

This study investigated the potential of PSMD1 and PSMD3, 19S regulatory components of the 26S proteasome, as novel targets for cancer therapy. Analysis of data from TCGA and CPTAC databases revealed a correlation between the expression of these proteins and overall survival in various cancers. These findings suggest that targeting PSMD1 and PSMD3 may be a promising strategy for cancer prognosis and treatment.

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

22.

Safety of proteasome inhibitors for treatment of multiple myeloma.

Author: SchlaferDanielle, ShahKatherine S, PanjicElyse Hall, LonialSagar

Multiple myeloma treatment
Peripheral neuropathy
Resistance development

This review focuses on the safety data from clinical trials for the three approved proteasome inhibitors (PIs) and how to manage adverse effects. The review also includes a summary of efficacy data from select clinical trials.

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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