• Paul G Richardson, Robert L Schlossman, Melissa Alsina, Donna M Weber, Steven E Coutre, Cristina Gasparetto, Sutapa Mukhopadhyay, Michael S Ondovik, Mahmudul Khan, Carole S Paley, and Sagar Lonial.
• Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
• Blood. 2013 Oct 3;122(14):2331-7.

AbstractPanobinostat 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 www.clinicaltrials.gov as #NCT01083602.

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