The addition of panobinostat to bortezomib and dexamethasone (PAN-BTZ-Dex) improved outcomes in patients with multiple myeloma who had received prior treatment with immunomodulatory drugs (IMiDs), prior bortezomib plus an IMiD, and two or more prior regimens including bortezomib and an IMiD.
Subgroup analysis of the PANORAMA phase III trial of patients with relapsed or relapsed and refractory multiple myeloma (MM) reported median progression-free survival (PFS) with PAN-BTZ-Dex versus placebo-BTZ-Dex (Pbo-BTZ-Dex) in groups defined by prior treatment: prior IMiD (12.3 vs. 7.4 months; hazard ratio, 0.54; 95% confidence interval, 0.43-0.68), prior bortezomib plus IMiD (10.6 vs. 5.8 months; HR, 0.52; 95% CI, 0.36-0.76), and two or more prior regimens including bortezomib and an IMiD (12.5 vs. 4.7 months; HR, 0.47; 95% CI, 0.31-0.72) (Blood. 2016 Feb 11. doi: 10.1182/blood-2015-09-665018).
Dr. Paul G. Richardson
The greatest difference in median PFS between the panobinostat and placebo arms (7.8 months) was observed among patients who had received two or more prior regimens including bortezomib and an IMiD, a population with a poorer prognosis and an urgent unmet need, according to investigators.
“Panobinostat represents a novel addition to the MM treatment armamentarium by introducing an agent with a novel mechanism of action. Novel agents are needed to address the ongoing unmet need in patients who progress on bortezomib and IMiDs as a strategy to overcome therapeutic resistance,” wrote Dr. Paul G. Richardson of the Dana Farber Cancer Institute, Boston, and his colleagues, adding that since the deacetylase inhibitor “acts on distinct epigenetic and protein metabolism pathways, it is uniquely suited to provide benefit in patients previously treated with proteasome inhibitors and/or IMiDs.”
The analysis examined treatment outcomes from the PANORAMA trial, including 485 patients who had received prior IMiD (63% of total population), 193 who received prior bortezomib plus IMiD (25% of total population), and 147 who received two or more prior regimens including bortezomib and an IMiD (19% of total population).
Common adverse events (AEs) by treatment subgroups were similar to those of the overall trial population, which were increased in the PAN-BTZ-Dex compared with the placebo arm. The most common nonhematologic AE was diarrhea and the most common hematologic abnormality was thrombocytopenia.
The PANORAMA 1 study was funded by Novartis Pharmaceuticals. Dr. Richardson reported having no disclosures. Several of his coauthors reported ties to industry.