Panobinostat and Carfilzomib Combination Appears Safe and Effective in Relapsed/Refractory Multiple Myeloma
In patients with relapsed/refractory multiple myeloma, the combination of panobinostat (Farydak) and carfilzomib (Kyprolis) appears to be safe and effective, according to a phase I/II study by Berdeja et al in Haematologica. Further evaluation of this combination treatment is warranted to establish the optimal dose and schedule.
Although the therapeutic options, and survival rates, for patients with multiple myeloma have improved over the past 2 decades, multiple myeloma is generally considered to be an incurable malignancy. The majority of patients undergo multiple cycles of chemotherapy, which become less effective as patients relapse. Researchers continue to study new single and combination therapies that may address this problem.
Berdeja and colleagues conducted a study examining the efficacy and safety of the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma. Carfilzomib is approved as a single agent for the treatment of multiple myeloma in patients who received at least two prior therapies, and panobinostat was the first histone deacetylase inhibitor approved for the treatment of multiple myeloma.
Study Details
Included in the study were 44 patients with relapsed/refractory myeloid leukemia. The study was divided into two phases. The first phase (n = 13) was to determine the maximum tolerated dose of the combination therapy. These patients were treated at four different dose levels.
The second phase (n = 31) was to assess the efficacy and safety of the combination therapy. These patients were treated at the highest dose level (30 mg of panobinostat and 20/45 mg/m2 of carfilzomib). The median number of prior therapies was five (range = 1–10); 89% of patients had received bortezomib (Velcade), 89% had received prior immune-modulating drugs, and 52% had had a prior stem cell transplantation.
The median age of patients was 66 years (range = 41–82), and 61% of patients were female. A total of 18 patients (41%) discontinued participation in the study due to disease progression, and 4 patients (9%) discontinued treatment due to treatment-related adverse events.
Overall Response Rate of 67%
The overall response rate in all patients was 67%. The overall response rate for all patients treated at the highest dose level was 72%.
Prior treatments did not appear to impact the overall response rates. The overall response rate for all patients who previously received bortezomib was 70%. Patients who were refractory to bortezomib, immune-modulating drugs, or both had an overall response rate of 67%, 75%, and 80%, respectively.
The overall survival rate at 24 months was 67%. At this time, the median overall survival has not been reached.
In regard to safety, grade 3/4 treatment-related adverse events included thrombocytopenia (38%), neutropenia (21%), fatigue (11%), anemia (9%), and hypertension (9%). Diarrhea, nausea and vomiting, and thrombocytopenia were the most commonly reported toxicities. Three patients discontinued treatment due to treatment-related toxicity. The toxicity associated with panobinostat often disappeared during the weeks off therapy; however, the toxicities returned with subsequent drug administration.
Closing Thoughts
The key finding of this study is that the combination of carfilzomib and the oral panobinostat appeared to be safe and effective at all dose levels. The researchers noted that further evaluation of this combination is warranted and will help establish the optimal dose and schedule.
The investigators concluded, “The combination of panobinostat and carfilzomib is feasible and effective in relapsed/refractory multiple myeloma patients.”
Jesus G. Berdeja, MD, of the Sarah Cannon Research Institute, Nashville, Tennessee,is the corresponding author of this article in Haematologica. The authors reported no potential conflicts of interest.
This study was supported in part by grants from Novartis and Onyx. For full disclosure of the study authors, visit www.haematologica.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
