In the following video, Dr Charlotte Pawlyn explains how histone deacetylase inhibitors work in treating myeloma.
Panobinostat (Farydak®) is the first histone deacetylase (HDAC) inhibitor to be approved as a treatment for myeloma. HDAC inhibitors are a relatively new class of anti-cancer drug which work by blocking the actions of HDAC proteins. They cause key genes responsible for cell cycle progression and cell proliferation to be switched off, which ultimately leads to myeloma cell death. Currently, HDAC inhibitors are not used on their own but always in combination with another agent as they are most effective in combination.
It is licensed across Europe for use in combination with bortezomib and dexamethasone for relapsed and/or refractory myeloma patients who have received at least two previous lines of treatment including bortezomib and an immunomodulatory drug.
Panobinostat is approved within its licensed indication by all UK HTA bodies and therefore available for NHS patients.
Patients taking panobinostat should be monitored for thrombocytopenia, neutropenia and anaemia. Some patients may need to be supported with GCSF.
Gastrointestinal toxicity including diarrhoea, nausea or vomiting is common and in severe cases, dose reduction or a temporary stop to treatment may be necessary. If used with bortezomib, then it is often advised using bortezomib once weekly. An anti-diarrhoeal such as loperamide should be prescribed at the first signs of abdominal cramp or onset of diarrhoea. Nurses should ensure that patients are educated to prevent dehydration. Some patients may also require prophylactic anti-emetics.
Panobinostat has been reported to cause serious and fatal cardiac events, severe arrhythmias and electrocardiographic abnormalities. It is important therefore that a baseline ECG is taken and the QT interval must be < 480 msec before treatment can be started. Cardiac function should be monitored throughout treatment.
Further investigations with panobinstat are ongoing to identify effective combinations with other anti-myeloma drugs such as ixazomib, carfilzomib and lenalidomide in relapsed and/or refractory patients. It is also being tested in the front-line setting.
San Miguel J et al. (2016) The role of panobinostat plus bortezomib and dexamethasone in treating relapsed or relapsed and refractory multiple myeloma: a European perspective. Adv. Ther. 33(11): 1896-1920.
San-Miguel J et al. (2014) Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol. 15(11): 1195-1206.