Carfilzomib, Panobinostat, Dexamethasone: Novel Combination in Resistant Myeloma
Posted: Monday, November 18, 2019
The results of a phase I/Ib study published in Haematologica show that as in other patients with relapsed or refractory multiple myeloma, those with higher degrees of proteasome inhibitor and immunomodulatory drug refractoriness demonstrate high response rates to the combination of the proteasome inhibitor carfilzomib and panobinostat (a pan-deacetylase inhibitor). Also, wrote the research team, the study is the first to report the efficacy and safety of carfilzomib/panobinostat with weekly dexamethasone.
Adding dexamethasone to the regimen improved the overall response rate from 18% to 53% and prolonged overall survival from 10 to 18.2 months. Elisabet E. Manasanch, MD, of The University of Texas MD Anderson Cancer Center in Houston, and colleagues posited that the triplet regimen “could be used as a bridge therapy in patients who are highly refractory or if other therapies are not readily available.”
In phase Ia of the trial, the maximum recommended dose of the combination was determined to be the largest of the four tested, for both carfilzomib and panobinostat; the primary objective in phase Ib of the trial was to determine the overall response rate of the combination. In total, 47 patients (46 evaluable for response), all refractory to either bortezomib or an immunomodulatory drug, were treated. The overall response rate was 37%, and the clinical benefit rate was 54%. For those refractory to both proteasome inhibitors and immunomodulatory drugs, the overall response rate was 17%.
Dexamethasone could be added at the investigator’s discretion during phase Ib. For patients treated with (n = 17) or without (n = 11) dexamethasone, the overall response rate was 53% versus 18%, and the clinical benefit rate was 65% versus 36%, respectively. For the patients receiving dexamethasone who were refractory to both proteasome inhibitors and immunomodulatory drugs, the overall response and clinical benefit rates were lower at 33% and 50%, respectively.
Disclosure: For full disclosures of the study authors, visit haematologica.org.