Panobinostat plus bortezomib and dexamethasone is tolerable and effective for relapsed/refractory (R/R) multiple myeloma in patients who had failed multiple lines of therapy, according to a study published in Clinical Lymphoma, Myeloma & Leukemia.
The phase 3 PANORAMA-1 trial demonstrated that the panobinostat plus bortezomib and dexamethasone regimen significantly prolonged progression-free survival (PFS) by 4 months, leading to US FDA approval for the treatment of patients with R/R multiple myeloma. However, some aspects of the study design were limited as PANORAMA-1 excluded patients who failed previous bortezomib therapy and only allowed for intravenous bortezomib administration, eliciting concerns about tolerability.
For this treatment-expansion study, researchers assigned 39 heavily treated patients with R/R multiple myeloma to receive the panobinostat, bortezomib, and dexamethasone (PANEX) protocol; PANEX was designed to provide access to panobinostat and additional data before commercial availability in the United States. In contrast with the PANORAMA-1 study, investigators were able to administer bortezomib subcutaneously, and patients who failed bortezomib previously were eligible.
Overall, 87% of patients received subcutaneous bortezomib. Results showed that of the 39 study participants, 22 achieved a partial response for an overall response rate (ORR) of 56%. Seven patients (18%) had a best response of minimal response, and 9 (23%) patients had a best response of no change. All patients in the study achieved a best response of stable disease or better.
The safety profile of PANEX was comparable to those previously reported. The most frequently reported grade 3 or 4 adverse events included thrombocytopenia, fatigue, dehydration, and diarrhea, and key all-grade adverse events associated with treatment included pneumonia, asthenia, vomiting, and peripheral neuropathy.
The authors concluded that “overall, data from the PANEX trial support regulatory approval of panobinostat plus bortezomib and dexamethasone and suggest the potential tolerability benefits of subcutaneous bortezomib in this regimen.”
Hansen VL, Coleman M, Elkins S, et al. An expanded treatment protocol of panobinostat plus bortezomib and dexamethasone in patients with previously treated myeloma[published online March 13, 2018]. Clin Lymphoma Myeloma Leuk. doi: 10.1016/j.clml.2018.03.002