Adding Pan-Deacetylase Inhibitor Panobinostat to Velcade and Dexamethasone Improves Progression-Free Survival in Relapsed Myeloma
In the phase III PANORAMA1 trial reported in The Lancet Oncology San-Miguel and colleagues found that adding the pan-deacetylase inhibitor panobinostat to Velcade ® (bortezomib) and dexamethasone improved progression-free survival in patients with relapsed or relapsed and refractory multiple myeloma.
Multiple myeloma is a cancer of plasma cells, which are a special type of white blood cell that are part of the body’s immune system. Patients with multiple myeloma have increased numbers of abnormal plasma cells that may produce increased quantities of dysfunctional antibodies detectable in the blood and/or urine.
Panobinostat is a drug that belongs to a class of drugs called histone deacetylase (HDAC) inhibitors, which work by increasing the production of proteins that slow cell division and cause cell death. It is being studied in myeloma as well as other blood cancers and solid tumors. Early studies have shown that panobinostat in combination with Velcade more effectively kills myeloma cells than either drug alone.
In the current clinical trial 768 patients from 215 centers in 34 countries who had relapsed or relapsed and refractory multiple myeloma were treated with either panobinostat, Velcade, and dexamethasone or a standard treatment regimen of Velcade, and dexamethasone and directly compared.
Patients in the panobinostat treatment group were more likely to experience diarrhea and low platelet and white blood cell counts often resulting in the discontinuation of treatment. Panobinostat treated patients however experienced an improvement in time to cancer progression from 8 to 12 months with over twice as many patients surviving 2 years from treatment.
Although panobinostat was associated with more toxicity especially to the bone marrow, its addition to a Velcade treatment regimen clearly improved time to cancer progression. Longer follow up is required to determine any overall survival benefit. Use of panobinostat earlier in the management of myeloma will likely be associated with fewer side effects.
Reference: San-Migule J, Hungira V, Yoon S-S, et al. 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. The Lancet Oncology, Volume 15, Issue 11, Pages 1195 – 1206, October 2014.
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