Abstract
Panobinostat represents a potent oral nonselective pan-histone deacetylase inhibitor (HDAC) with activity in myeloma patients. It has been approved by the FDA and EMA in combination with bortezomib and dexamethasone for the treatment of multiple myeloma, in patients who have received at least two prior regimens, including bortezomib and an immunomodulatory agent. In order to further explore its clinical potential, it is evaluated in different combinations in relapsed/refractory and newly diagnosed multiple myeloma. This review focuses on available data about panobinostat's pharmacology and its role in clinical practice. This review will reveal panobinostat's efficacy as antimyeloma treatment, describing drug evolution from preclinical experimental administration to administration in phase III trials, which established its role in current clinical practice. Based on the latest data, we will present its mechanism of action, its efficacy, and most important issues regarding its toxicity profile. We will further try to shed light on its role in current and future therapeutic landscape of myeloma patients. Panobinostat retains its role in therapy of multiple myeloma because of its manageable toxicity profile and its efficacy, mainly in heavily pretreated multiple myeloma patients. These characteristics make it valuable also for novel regimens in combination with second-generation proteasome inhibitors, IMiDs, and monoclonal antibodies. Results of ongoing trials are expected to shed light on drug introduction in different therapeutic combinations or even at an earlier level of disease course.
Highlights
Multiple myeloma is a plasma cell dyscrasia characterized by clonal plasma cell proliferation within bone marrow and increased production of monoclonal paraprotein, excreted in the blood or urine
In 2018, it was estimated that 30,770 patients in the USA would be diagnosed with multiple myeloma and 12,770 patients will succumb to myeloma disease [4]
It is estimated that in 2018, 159,985 patients will be diagnosed with multiple myeloma and 106,105 patients will expire due to myeloma disease [5]
Summary
Multiple myeloma is a plasma cell dyscrasia characterized by clonal plasma cell proliferation within bone marrow and increased production of monoclonal paraprotein, excreted in the blood or urine It mainly affects elderly population, with a median age of diagnosis at approximately 70 years [1]. Before the introduction of more advanced novel agents (carfilzomib and pomalidomide), patients with relapsed/refractory myeloma after initial therapy with proteasome inhibitors and IMiDs attained a dismal prognosis, with a median PFS of 5 months and a median OS not exceeding 9 months [32].
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