Effects of ixazomib: A Synthesis of Findings from 23 Studies

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Original Abstract of the Article

Major Research Findings

Ixazomib is an oral proteasome inhibitor that has been approved for the treatment of multiple myeloma, a type of blood cancer. It has been shown to be effective in combination with other drugs, such as lenalidomide and dexamethasone, in patients with relapsed or refractory multiple myeloma. 9 1 Ixazomib has also shown promising results in combination with other drugs for the treatment of acute lymphoblastic leukemia. 5 Furthermore, a new class of dual PARP-1/proteasome inhibitors has been developed, which shows synergistic effects in treating breast cancer. 21 These inhibitors target both PARP-1 and the proteasome, effectively inhibiting DNA repair mechanisms in cancer cells.

Researchers have also investigated the effects of ixazomib on bone formation in patients with multiple myeloma. One study found that ixazomib increased bone volume in patients with multiple myeloma, suggesting a potential benefit for bone health in this patient population. 16 However, ixazomib can cause side effects, including cardiotoxicity, which may be caused by mitochondrial dysfunction. 2

Benefits and Risks

Benefits Summary

Ixazomib is a promising new oral proteasome inhibitor that has been shown to be effective in treating multiple myeloma and other cancers. It has a favorable safety profile compared to other proteasome inhibitors and can be administered orally, making it a convenient treatment option. Ixazomib may also have beneficial effects on bone health, potentially reducing bone loss associated with multiple myeloma.

Risk Summary

Ixazomib can cause side effects, including cardiotoxicity, which may limit its use in some patients. Furthermore, interactions with dietary flavonoids containing catechol moieties may interfere with the anticancer activity of ixazomib and other boronic acid-based drugs. 14

Comparison Across Studies

Similarities Across Studies

Across multiple studies, ixazomib has shown promise as an effective treatment for multiple myeloma, particularly in combination with other drugs. 9 1 Ixazomib has also been found to be well-tolerated, with a favorable safety profile compared to other proteasome inhibitors. 20 However, some studies have found that ixazomib may not be effective in patients who have previously relapsed on other proteasome inhibitor-containing regimens. 12

Differences Across Studies

While the primary focus of research on ixazomib is its use in multiple myeloma, other studies have explored its potential in treating various other cancers, including acute lymphoblastic leukemia, mantle cell lymphoma, and even breast cancer. 5 3 21 These studies suggest that ixazomib may have a broader therapeutic application than initially thought.

Consistency and Contradictions in Results

While ixazomib has shown promising results in treating multiple myeloma, further research is needed to determine its efficacy in patients who have previously failed other proteasome inhibitor-based therapies. 12 Additionally, while the safety profile of ixazomib appears favorable compared to other proteasome inhibitors, more research is needed to understand the long-term effects of ixazomib treatment and its potential interactions with other drugs. 20

Practical Implications

Ixazomib is a valuable treatment option for patients with multiple myeloma, particularly those who have relapsed or are refractory to other therapies. However, it's crucial for healthcare providers and patients to be aware of the potential side effects and interactions with other drugs. Patients should be monitored closely for any adverse effects, and a careful assessment of risks and benefits should be conducted before initiating treatment.

Limitations of Current Research

While research on ixazomib has been promising, there are still limitations to consider. Long-term studies are needed to fully understand the long-term efficacy and safety profile of ixazomib. Additionally, further research is required to explore the potential applications of ixazomib in treating other types of cancers, including solid tumors.

Future Research Directions

Future research should focus on investigating the long-term efficacy and safety of ixazomib, particularly in patients who have relapsed on other proteasome inhibitor-based therapies. Additionally, exploring the potential synergistic effects of ixazomib with other drugs, particularly in treating other types of cancer, is crucial. Finally, further investigation into the mechanisms of action of ixazomib and its impact on bone health is warranted.

Conclusion

Ixazomib is a promising oral proteasome inhibitor that has shown efficacy in treating multiple myeloma and other cancers. It offers a convenient and well-tolerated treatment option for patients. However, it's crucial to be aware of the potential side effects and interactions with other drugs. Continued research is necessary to understand the long-term effects of ixazomib and its full potential in treating a wider range of cancers.

Literature analysis of 23 papers
Positive Content
22
Neutral Content
0
Negative Content
1
Article Type
1
0
0
3
23
1.

In-class transition (iCT) of proteasome inhibitor-based therapy: a community approach to multiple myeloma management.

Author: RifkinRobert M, GirniusSaulius K, NogaStephen J, BirhirayRuemu E, KambhampatiSuman, MandaSudhir, LyonsRoger M, YimerHabte A, CherepanovDasha, LloydEric, WhiddenPresley, RichterJoshua

Improved MM outcomes
Prolonged PI-based therapy

Long-term proteasome inhibitor (PI) treatment can improve outcomes for multiple myeloma (MM) patients. This study evaluated the efficacy and safety of transitioning to all-oral ixazomib-lenalidomide-dexamethasone (IRd) after induction therapy in transplant-ineligible patients with newly diagnosed MM. Results showed promising efficacy and a tolerable safety profile, supporting the use of iCT to IRd for prolonged PI-based therapy.

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

2.

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

3.

Ixazomib With or Without Rituximab Following Maintenance Autologous Stem Cell Transplant in Mantle Cell Lymphoma: A Single-Center Phase I Trial.

Author: RomancikJason T, ChenZhengjia, AllenPamela B, WallerEdmund K, VallaKelly, ColbertAmanda, RosandCecilia, PalmerAlexandra F, FlowersChristopher R, CohenJonathon B

Complete remission
Myelosuppression

This single-center phase I trial investigating post-transplant maintenance with ixazomib in patients with mantle cell lymphoma (MCL) found that the current dose and schedule of ixazomib, especially when combined with rituximab, results in unacceptable hematologic toxicity.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/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

5.

Ixazomib in addition to chemotherapy for the treatment of acute lymphoblastic leukemia in older adults.

Author: AmreinPhilip, BallenKaren, StevensonKristen, BrunnerAndrew, HobbsGabriela, HockHanno, McAfeeSteven, MoranJenna, BergeronMeghan, FosterJulia, BertoliChristina, McGreggorKristin, MacreaMolly, BurkeMeghan, BehnamTanya, SomTina, RamosAura, VartanianMegan, Lombardi StoryJennifer, ConnollyChristine, BlonquistTraci, NeubergDonna, FathiAmir

ALL treatment

This study assessed the safety and efficacy of adding ixazomib, an oral proteasome inhibitor, to a multi-agent treatment regimen for older adults with acute lymphoblastic leukemia (ALL). The study found that ixazomib was well-tolerated and achieved high remission rates in this patient population.

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.

Efficacy and Safety of Ixazomib Plus Lenalidomide and Dexamethasone Following Injectable PI-Based Therapy in Relapsed/Refractory Multiple Myeloma.

Author: AbeYu, SasakiMakoto, TakezakoNaoki, ItoShigeki, SuzukiKazuhito, HandaHiroshi, ChouTakaaki, YoshidaTakahiro, MoriIkuo, ShinozakiTomohiro, SuzukiKenshi

Improved PFS
RRMM treatment
Tolerable treatment
Decreased neutrophil count
Decreased platelet count

This study evaluated the efficacy and safety of ixazomib plus lenalidomide and dexamethasone (IRd) following injectable PI-based therapy for relapsed/refractory multiple myeloma (RRMM). IRd demonstrated tolerable and efficacious results in this setting, suggesting its potential as a treatment option for patients with RRMM.

Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

8.

Proteasome Inhibitors and Their Potential Applicability in Osteosarcoma Treatment.

Author: Van StiphoutCassidy M, LuuAnita K, Viloria-PetitAlicia M

OS treatment

This review summarizes the biological effects and latest findings from clinical trials investigating proteasome inhibitor (PI)-based treatments for osteosarcoma (OS). PIs may improve outcomes for patients diagnosed with OS.

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.

Population pharmacokinetic/pharmacodynamic joint modeling of ixazomib efficacy and safety using data from the pivotal phase III TOURMALINE-MM1 study in multiple myeloma patients.

Author: SrimaniJaydeep K, DiderichsenPaul M, HanleyMichael J, VenkatakrishnanKarthik, LabotkaRichard, GuptaNeeraj

Improve myeloma
Diarrhea
Rash

This paper presents an integrated pharmacokinetic/pharmacodynamic modeling approach to describe both safety and efficacy outcomes of ixazomib, a proteasome inhibitor for multiple myeloma. The model incorporates covariates like prior immunomodulatory therapy and race to improve its predictive capabilities for individual patients.

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.

A phase 1/2 study of ixazomib in place of bortezomib or carfilzomib in a subsequent line of therapy for patients with multiple myeloma refractory to their last bortezomib or carfilzomib combination regimen.

Author: DanielyDavid, ForouzanEli, SpektorTanya M, CohenAlexa, BitranJacob D, ChenGigi, MoeziMehdi M, BessudoAlberto, HromJohn, EshaghianShahrooz, SwiftRegina A, EadesBenjamin M, KimClara, LimStephen, BerensonJames R

Ixazomib tolerability
Grade 3 adverse events
Ixazomib ineffectiveness

Ixazomib, a proteasome inhibitor, was investigated as a replacement for bortezomib or carfilzomib in patients with multiple myeloma who had relapsed on prior regimens containing those drugs. The results showed that ixazomib was not an effective replacement and did not delay disease progression.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
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.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

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

15.

Proteasome inhibitors in medullary thyroid carcinoma: time to restart with clinical trials?

Author: FanciulliGiuseppe, ModicaRoberta, La SalviaAnna, GrossrubatscherErika Maria, FlorioTullio, FerraùFrancesco, VeresaniAlessandro, RussoFlaminia, ColaoAnnamaria, FaggianoAntongiulio

MTC treatment

Medullary thyroid cancer (MTC) is a rare thyroid tumor that is challenging to manage in advanced stages. Proteasome inhibitors (PrIn) are a potential treatment option, as they have been shown to improve outcomes in other malignancies by inhibiting cell proliferation and causing apoptosis.

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

16.

Increased Bone Volume by Ixazomib in Multiple Myeloma: 3-Month Results from an Open Label Phase 2 Study.

Author: Diaz-delCastilloMarta, GundesenMichael Tveden, AndersenChristian Walther, NielsenAnne Lerberg, MøllerHanne Elisabeth Højsgaard, VinholtPernille Just, AsmussenJon Thor, KristensenIda Bruun, NyvoldCharlotte Guldborg, AbildgaardNiels, Levin AndersenThomas, LundThomas

MM treatment

Ixazomib, an oral proteasome inhibitor (PI) for multiple myeloma (MM), was found to have a positive effect on bone formation in a phase II clinical trial. While NaF-PET scans showed no change in bone formation ratios, bone biopsies revealed a significant increase in bone volume after three cycles of ixazomib treatment. This suggests that ixazomib induces bone formation by decreasing bone resorption and promoting longer bone formation events, making it a potential candidate for future maintenance treatment in MM patients.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
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

18.

Phase 2 trial of ixazomib, cyclophosphamide, and dexamethasone for previously untreated light chain amyloidosis.

Author: MuchtarEli, GertzMorie A, LaPlantBetsy R, BuadiFrancis K, LeungNelson, O'BrienPatrick, BergsagelP Leif, FonderAmie, HwaYi Lisa, HobbsMiriam, HelgesonDania K, BradtErin E, GonsalvesWilson, LacyMartha Q, KapoorPrashant, SiddiquiMustaqueem, LarsenJeremy T, WarsameRahma, HaymanSuzanne R, GoRonald S, DingliDavid, KourelisTaxiarchis V, DispenzieriAngela, RajkumarS Vincent, KumarShaji K

Effective AL amyloidosis treatment
Favorable toxicity profile
Improved survival
Hematologic adverse events
Nonhematologic adverse events

Bortezomib, a proteasome inhibitor, is effective in treating light chain (AL) amyloidosis, but its intravenous administration limits its use. This study evaluated the efficacy of ixazomib, an oral proteasome inhibitor, in combination with cyclophosphamide and dexamethasone in newly diagnosed AL amyloidosis patients. The study found a hematologic response rate of 63% with acceptable toxicity, warranting further evaluation of ixazomib in upfront treatment settings.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
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

19.

A phase I/II study of ixazomib, pomalidomide, and dexamethasone for lenalidomide and proteasome inhibitor refractory multiple myeloma (Alliance A061202).

Author: VoorheesPeter M, SumanVera J, TuchmanSascha A, LaubachJacob P, HassounHani, EfeberaYvonne A, MulkeyFlora, Bova-SolemMisty, SantoKatelyn, CarlisleDestin, McCarthyPhilip L, RichardsonPaul G

Multiple myeloma treatment
Constitutional adverse events
Gastrointestinal adverse events
Hematologic adverse events

Ixazomib (IXA) is a promising oral proteasome inhibitor that has demonstrated activity in bortezomib-resistant multiple myeloma (MM). A phase I/II clinical trial showed that IXA, combined with pomalidomide (POM) and dexamethasone (DEX), was well tolerated and demonstrated a significant overall response rate in patients with lenalidomide (LEN)/PI-refractory MM.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number 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, 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

21.

Design and synthesis of the first PARP-1 and proteasome dual inhibitors to treat breast cancer.

Author: HeHualong, YangWan, ShiYaojie, ChenXin, ChenXinyi, HuXiang, LiXinyue, YangYingyue, LiuZhihao, YeTinghong, WangNingyu, YuLuoting

Inhibit cancer cell proliferation

This study describes the design and synthesis of the first dual PARP-1 and proteasome inhibitor, based on Olaparib and Ixazomib. These dual inhibitors demonstrate excellent proliferation inhibition and synergistic effects on cells resistant to PARP-1 inhibitors.

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

Language : English

22.

Combined inhibition of BCR-ABL1 and the proteasome as a potential novel therapeutic approach in BCR-ABL positive acute lymphoblastic leukemia.

Author: MaletzkeSaskia, SalimiAzam, VieriMargherita, SchroederKema Marlen, SchemionekMirle, MasoulehBehzad Kharabi, BrümmendorfTim H, KoschmiederSteffen, AppelmannIris

ALL treatment

This study investigates the synergistic cytotoxic effects of combining tyrosine kinase inhibitors (TKIs) with proteasome inhibitors in BCR-ABL+ acute lymphoblastic leukemia (ALL) cells. The findings suggest that this combination could potentially expand the therapeutic options for patients with BCR-ABL+ ALL.

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

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