Panobinostat 20mg with bortezomib, dexamethasone, and low-dose thalidomide is a safe and efficacious treatment combination for patients with relapsed multiple myeloma, according to a study published in The Lancet Haematology.1

Findings from the phase 3 PANORAMA 1 trial (ClinicalTrials.gov Identifier: NCT01023308) led to the approval of panobinostat for treatment, in conjunction with bortezomib and dexamethasone, of patients who received at least 2 prior lines of therapy. This treatment regimen was, however, associated with incidence of grade 3-4 diarrhea, nausea, and asthenia.

For the present phase 1/2 MUK-six trial (ClinicalTrials.gov Identifier: NCT02145715), researchers attempted to determine both the optimal and maximum panobinostat dosage, as well as whether administering bortezomib subcutaneously (rather than intravenously, as was done in the PANORAMA 1 trial) and adding low-dose thalidomide would together reduce toxicity but preserve or improve treatment efficacy.


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Fifty-seven patients were enrolled; 16 patients were included in a dose-escalation phase to determine the optimal and maximum panobinostat dosage. One dosage-limiting toxicity event was reported at 20mg, and, though this event was not linked to the study regimen, the authors were unable to determine the maximum drug dosage.

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The researchers concluded that the optimal panobinostat dosage is 20mg. The intention-to-treat population included 46 patients; of this group, 91% achieved a partial response or better, and 46% achieved a very good partial response or better. The incidence of grade 3-4 events was also lower than in the PANORAMA 1 trial.

Panobinostat 20mg is, according to the authors, an efficacious and relatively safe treatment, in combination with bortezomib, dexamethasone, and thalidomide, in this patient population.

Reference

  1. Popat R, Brown SR, Flanagan L, et al. Bortezomib, thalidomide, dexamethasone, and panobinostat for patients with relapsed multiple myeloma (MUK-six): a multicentre, open-label, phase 1/2 trial. Lancet Haematol. 2016 Nov 11. doi: 10.1016/S2352-3026(16)30165-X [Epub ahead of print]