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The potential of panobinostat as a treatment option in patients with relapsed and refractory multiple myeloma.

ABSTRACT: Panobinostat is an investigational and potent histone deacetylase inhibitor (HDACi) that has shown promise as an antimultiple myeloma agent in the preclinical setting. In this review, we discuss the rationale for the use of panobinostat as a combination therapy for multiple myeloma and provide an overview of recent and ongoing clinical trials testing the safety and efficacy of panobinostat for the treatment of the disease.

SUBMITTER: Andreu-Vieyra CV

PROVIDER: S-EPMC4250267 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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The potential of panobinostat as a treatment option in patients with relapsed and refractory multiple myeloma.

Andreu-Vieyra Claudia V CV Berenson James R JR

Therapeutic advances in hematology 20141201 6

Panobinostat is an investigational and potent histone deacetylase inhibitor (HDACi) that has shown promise as an antimultiple myeloma agent in the preclinical setting. In this review, we discuss the rationale for the use of panobinostat as a combination therapy for multiple myeloma and provide an overview of recent and ongoing clinical trials testing the safety and efficacy of panobinostat for the treatment of the disease. ...[more]

PMID: 25469210

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Panobinostat PK/PD profile in combination with bortezomib and dexamethasone in patients with relapsed and relapsed/refractory multiple myeloma.

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Treatment of relapsed and refractory multiple myeloma.

Project description:The therapeutic strategy for relapsed and refractory multiple myeloma (RRMM) integrates a holistic approach regarding patient, disease, and drug-related factors. Patient-related factors include age, frailty status, and underlying comorbidities, especially cardiovascular and renal diseases and peripheral neuropathies that affect tolerability to multiple drug combinations or transplantations. Disease-related factors encompass these multiple patient-related factors, particularly the aggressiveness of the disease and cytogenetics. Regarding drug-related factors, the approval of novel proteasome inhibitors (such as carfilzomib and ixazomib), immunomodulatory agents (such as pomalidomide), monoclonal antibodies (such as daratumumab and elotuzumab), and new classes of drugs increasingly makes the choice treatment more complex and necessitates a comprehensive summary and an update of the efficacy and toxicities of each antimyeloma drug and its combinations. Further, careful monitoring of the side effects and supportive care throughout the course of treatment are important to achieve better outcomes for patients with RRMM.

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Phase 1 open-label study of panobinostat, lenalidomide, bortezomib + dexamethasone in relapsed and relapsed/refractory multiple myeloma.

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| S-EPMC7873303 | biostudies-literature

Role of Histone Deacetylase Inhibitors in Relapsed Refractory Multiple Myeloma: A Focus on Vorinostat and Panobinostat.

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| S-EPMC4995883 | biostudies-other

Phase I/II study of the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma.

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| S-EPMC4420216 | biostudies-literature

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| S-EPMC6320362 | biostudies-literature

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| S-EPMC4869663 | biostudies-literature

The Role of Panobinostat Plus Bortezomib and Dexamethasone in Treating Relapsed or Relapsed and Refractory Multiple Myeloma: A European Perspective.

Project description:Panobinostat is an oral pan-histone deacetylase inhibitor developed by Novartis. Panobinostat acts via epigenetic modification and inhibition of the aggresome pathway. In August 2015, the European Commission authorized panobinostat for use in combination with bortezomib and dexamethasone for the treatment of relapsed or relapsed and refractory multiple myeloma (MM) in patients who have received ≥2 prior regimens including bortezomib and an immunomodulatory drug. In January 2016, the National Institute for Health and Care Excellence recommended panobinostat for use in the same combination and patient population. The authorization and recommendation were based on results from the pivotal phase 3 PANORAMA 1 (NCT01023308) clinical trial, which demonstrated an improvement in median progression-free survival of 7.8 months for the three-drug combination compared with placebo plus bortezomib and dexamethasone in this patient population. This review will discuss the current treatment landscape for relapsed/refractory MM, the mechanism of action of panobinostat, clinical data supporting the European authorization, concerns about safety and strategies for mitigating toxicity, and how panobinostat fits into the current MM landscape in Europe.FundingEditorial support, funded by Novartis Pharmaceuticals.

| S-EPMC5083773 | biostudies-literature

Lenalidomide for the treatment of relapsed and refractory multiple myeloma.

Project description:Lenalidomide is an amino-substituted derivative of thalidomide with direct antiproliferative and cytotoxic effects on the myeloma tumor cell, as well as antiangiogenic activity and immunomodulatory effects. Together with the introduction of bortezomib and thalidomide, lenalidomide has significantly improved the survival of patients with relapsed and refractory myeloma. The most common adverse events associated with lenalidomide include fatigue, skin rash, thrombocytopenia, and neutropenia. In addition, when lenalidomide is combined with dexamethasone or other conventional cytotoxic agents, there is an increase in the incidence of venous thromboembolic events. There is now evidence that continued treatment with lenalidomide has a significant impact on survival by improving the depth and duration of response. This highlights the value of adverse event management and appropriate dose adjustments to prevent toxicity, and of allowing continued treatment until disease progression. In this review, we will discuss the different lenalidomide-based treatment regimens for patients with relapsed/refractory myeloma. This is accompanied by recommendations of how to manage and prevent adverse events associated with lenalidomide-based therapy.

| S-EPMC3430086 | biostudies-literature

Selinexor in relapsed/refractory multiple myeloma.

Project description:Multiple myeloma (MM) represents an incurable hematologic malignancy. Despite significant advances over the past decade, with the advent of multiple new classes of anti-myeloma agents, including immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies, patients ultimately relapse. Selinexor is a first-in-class exportin-1 inhibitor with activity in these multiply relapsed and refractory patients. Although the current Food and Drug Administration (FDA) approval is for the doublet of Selinexor in combination with dexamethasone, ongoing clinical trials are evaluating a number of combination regimens. These triplet and quadruplet, selinexor-based, regimens are showing significant activity in "triple-class" refractory patients. With appropriate combination drug choice, drug dosing, and supportive measures, patients with previously no viable options for therapy, now have multiple potential regimens to control their disease.

| S-EPMC7285937 | biostudies-literature

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