PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma BLOOD Richardson, P. G., Schlossman, R. L., Alsina, M., Weber, D. M., Coutre, S. E., Gasparetto, C., Mukhopadhyay, S., Ondovik, M. S., Khan, M., Paley, C. S., Lonial, S. 2013; 122 (14): 2331-2337


Panobinostat is an oral pan-deacetylase inhibitor that synergizes with bortezomib to inhibit both the aggresome and proteasome pathways in preclinical studies. PANORAMA 2 is a phase 2 trial of panobinostat in combination with bortezomib and dexamethasone to treat patients with relapsed and bortezomib-refractory multiple myeloma (with =2 prior lines of therapy, including an immunomodulatory drug, and patients who had progressed on or within 60 days of the last bortezomib-based therapy). Fifty-five heavily pretreated patients were enrolled (median, 4 prior regimens, including a median of 2 prior bortezomib-containing regimens). The overall response rate was 34.5% (1 near-complete response and 18 partial responses). An additional 10 patients achieved minimal response, for a clinical benefit rate of 52.7%. Median exposure and progression-free survival were 4.6 and 5.4 months, respectively. In patients who achieved a response, median time to response was 1.4 months, and median duration of response was 6.0 months. Common grade 3/4 adverse events, regardless of study drug relationship, included thrombocytopenia (63.6%), fatigue (20.0%), and diarrhea (20.0%). Only 1 patient had grade 3 peripheral neuropathy. Panobinostat, when combined with bortezomib and dexamethasone, can recapture responses in heavily pretreated, bortezomib-refractory multiple myeloma patients. This trial was registered at as #NCT01083602.

View details for DOI 10.1182/blood-2013-01-481325

View details for Web of Science ID 000326078200016

View details for PubMedID 23950178