Panobinostat in combination with bortezomib, thalidomide, and dexamethasone is active and well tolerated in patients with relapsed multiple myeloma, according to a study published in The Lancet Haematology.1
The pan histone deacetylase inhibitor panobinostat is approved by the US Food and Drug Administration in combination with bortezomib and dexamethasone for the treatment of patients with multiple myeloma who have received at least 2 prior regimens, including bortezomib and an immunomodulatory agent, such as lenalidomide and thalidomide; however, this regimen is associated with grade 3 to 4 diarrhea and fatigue in a quarter of patients.
Therefore, researchers sought to improve the safety of this combination and evaluate activity by incorporating low-dose thalidomide, using subcutaneous weekly bortezomib, and determining the maximum tolerated dose of panobinostat in this regimen.
For the multicenter, open-label, phase 1/2 MUK-six trial (ClinicalTrials.gov Identifier: NCT02145715), researchers enrolled 57 patients with relapsed, or relapsed and refractory, multiple myeloma who had received 1 to 4 prior regimens.
With only 1 case of a dose-limiting toxicity, which was grade 3 hyponatremia at the 20 mg dose, researchers determined that the recommended dose of panobinostat was 20 mg.
Among the 46 patients treated with panobinostat 20 mg, 91% (80% CI, 83.4-96.2) achieved the primary end point of a partial response or better.
The most common grade 3 or higher adverse events in the overall population were neutropenia in 26%, hypophosphatemia in 19%, and thrombocytopenia in 14%. Most adverse events were grade 1 to 2 and there were few instances of grade 3 to 4 diarrhea or fatigue.
Investigators observed 46 occurrences of serious adverse events in 27 patients, of which 14 cases were suspected to be related to the treatment regimen.