Photo courtesy of the CDC
The combination of vorinostat and bortezomib, with or without dexamethasone, can be active in patients with multiple myeloma (MM) that is refractory to novel treatments, according to researchers.
In a phase 2 trial, the combination produced an overall response rate of 11% among MM patients who were refractory to bortezomib and were either refractory to or could not receive treatment with an immunomodulatory agent (IMiD).
About 92% of patients had drug-related adverse events (AEs), and 20% had serious drug-related AEs.
These results were published in Clinical Lymphoma, Myeloma & Leukemia. The study was funded by Merck & Co., Inc., which markets vorinostat as Zolinza.
This trial (VANTAGE 095) enrolled 143 MM patients from 41 centers in 12 countries. The patients had a median age of 63 (range, 37-81) and had received a median of 4 prior lines of therapy (range, 2-17).
All 143 patients were considered refractory to previous bortezomib, which was defined as less than 25% response on therapy or progression during/less than 60 days after the completion of bortezomib therapy.
All but 1 patient had been exposed to 1 or more IMiDs (99.3%). Roughly 87% of patients exposed to IMiDs were considered to have disease refractory to at least 1 IMiD and 40% to at least 2 different IMiDs. Three percent of patients were considered ineligible for further IMiD-based therapy because of previous toxicities.
For this study, patients received 21-day cycles of bortezomib (1.3 mg/m2 intravenously; days 1, 4, 8, and 11) plus oral vorinostat at 400 mg/d on days 1 to 14.
If a patient had no change as the best response after 4 cycles of treatment or progressive disease after 2 cycles of treatment, oral dexamethasone at 20 mg on the day of and day after each dose of bortezomib could be added to the treatment regimen.
Patients were treated until disease progression, unacceptable toxicities, or withdrawal from the study.
One hundred and forty-two patients were evaluable for safety and efficacy. Fifty-seven of these patients received dexamethasone per protocol.
The overall response rate (partial response or better), as assessed by an independent adjudication committee, was 11.3%.
All 16 responses were partial responses. The median time to response was 44 days (range, 22-71), and the median duration of response was 211 days (range, 64-550 days).
Eleven patients (7.7%) had a minimal response, and 87 (61.3%) had stable disease.
The median progression-free survival was 3.13 months, and the median time to progression was 3.47 months. The median overall survival was 11.2 months, with a 2-year survival rate of 32%.
All 142 patients had at least 1 AE, and 131 (92.3%) had drug-related AEs. Most AEs were grade 3 (28.9%) or 4 (50.7%). Serious AEs occurred in 64.8% of patients, and serious drug-related AEs occurred in 20.4%.
Twenty-seven patients (19%) discontinued treatment due to an AE. And 24 patients (16.9%) died from an AE, although 18 of these deaths were attributable to progression of underlying MM.
The most common AEs were thrombocytopenia (69.7%), nausea (57.0%), diarrhea (53.5%), anemia (52.1%), and fatigue (48.6%).
