The addition of panobinostat to bortezomib and dexamethasone significantly extended PFS among patients with relapsed or relapsed/refractory multiple myeloma, according to results of the randomized phase 3 PANORAMA1 trial.
Preclinical studies showed panobinostat (LBH589, Novartis) — an oral pan-deacetylase inhibitor — has anti-myeloma activity when combined with bortezomib (Velcade, Millennium) and dexamethasone.
In the current study, Jesús F. San-Miguel, MD, PhD, head of the department of hematology at the University Hospital of Salamanca in Spain, and colleagues sought to compare bortezomib, dexamethasone and panobinostat with bortezomib, dexamethasone and placebo.
The analysis included 768 patients (median age, 63 years) with relapsed or relapsed/refractory multiple myeloma. About half of patients (48%) had received two or three prior regimens, and 57% had undergone prior autologous stem cell transplant.
All patients received 1.3 mg/m2 IV bortezomib on days 1, 4, 8 and 11, as well as 20 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11 and 12. Researchers then randomly assigned patients 1:1 to receive 20 mg oral panobinostat or placebo on days 1, 3, 5, 8, 10 and 12.
PFS served as the primary outcome measure. Median follow-up was 6.47 months for the panobinostat arm and 5.59 months for the placebo arm.
Researchers reported significantly longer median PFS among patients assigned panobinostat (11.9 months vs. 8.08 months; HR=0.63; 95% CI, 0.52-0.76). Although OS data were not mature at the time of analysis, median OS was 33.64 months in the panobinostat arm and 30.39 months among those who received placebo (HR=0.87; 95% CI, 0.69-1.10).
Patients assigned panobinostat demonstrated a higher combined rate of near complete response and complete response (27.6% vs. 15.7%), as well as a longer median duration of response (13.14 months vs. 10.87 months). However, the proportion of patients who demonstrated an overall response did not differ significantly between the panobinostat arm and placebo arm (60.7% vs. 54.6%).
Median duration of a partial response or better was 13.14 months with panobinostat vs. 10.87 months with placebo. Median time to partial response or better was 1.51 months in the panobinostat arm vs. 2 months in the placebo arm.
Researchers reported higher rates of grade 3 or grade 4 adverse events in the panobinostat arm. Those events included thrombocytopenia (67% vs. 31%), lymphopenia (53% vs. 40%) and diarrhea (26% vs. 8%).
“Our results suggest that panobinostat could be a useful addition to the treatment armamentarium for patients with relapsed or relapsed and refractory multiple myeloma,” San-Miguel and colleagues wrote. “Longer follow-up will be necessary to determine whether there is any effect on OS.”
Disclosure: The study was funded by Novartis Pharmaceuticals.