The combination of the investigational histone deacetylase inhibitor panobinostat (Faridak) with bortezomib (Velcade) and dexamethasone was able to recapture responses in 34.5% of heavily pretreated, bortezomib-refractory patients with multiple myeloma in the phase II PANORAMA 2 trial. The 55 patients enrolled at 12 trial sites had a median of four prior regimens, including two prior regimens with bortezomib. The responses at the end of the first treatment phase cycles included 1 near-complete response and 18 partial responses. “An additional 10 patients achieved minimal response, for a clinical benefit rate of 52.7%,” the researchers reported online in Blood.
“Responses in the remainder of patients consisted of stable disease in 20 patients (36.4%) and progressive disease in 3 patients (5.5%). Response could not be assessed in the remaining 3 patients (5.5%) due to insufficient or missing assessments,” the investigators added.
Study Design
The first treatment phase (cycles 1–8), consisted of panobinostat (3 times per week), bortezomib (twice per week), and dexamethasone (the day of and after bortezomib), administered on a 2-weeks-on/1-week-off schedule. Seventeen patients went on to the second treatment phase, which consisted of 6-week cycles (two 2-weeks-on/1-week-off repeating cycles), with bortezomib and dexamethasone reduced to one dose during the scheduled weeks.
At the time of data cutoff, seven patients remained on treatment. Among the 48 patients who did not go on to the second phase, the main reasons were disease progression and adverse events. There was one death.
Manageable Toxicities
The most common adverse events were diarrhea (70.9%), fatigue (69.1%), thrombocytopenia (65.5%), nausea (60.0%), and anemia (47.3%). The most common grade 3/4 adverse events were thrombocytopenia (63.6%), diarrhea and fatigue (20% for each), and anemia, neutropenia, and pneumonia (14.5% for each). “Overall, the combination of panobinostat with bortezomib and dexamethasone was tolerable, with manageable toxicities,” the researchers reported.
As the investigators noted, while front-line treatment of multiple myeloma often produces high response rates, nearly all patients eventually relapse and their prognosis worsens when they become refractory to treatment, including bortezomib, lenalidomide (Revlimid), and thalidomide (Thalomid). “Thus, novel agents that can recapture responses in bortezomib-refractory [multiple myeloma] patients are needed,” the researchers stated.
The combination of panobinostat, bortezomib, and dexamethasone is also being studied in a large phase III trial (PANORAMA 1). ■
Richardson PG, et al: Blood. August 15, 2013 (early release online).
