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Panobinostat combinations extends PFS in heavily pretreated, relapsed multiple myeloma
Treatment with panobinostat, bortezomib and dexamethasone significantly improved PFS in patients with relapsed and refractory multiple myeloma previously treated with bortezomib and immunomodulatory therapies, according to a subgroup analysis of a phase 3 study.
“Over the past decade there have been significant advancements in the development of treatments for patients with multiple myeloma, which have led to clear improvements in OS,” Paul G. Richardson, MD, clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, professor of medicine at Harvard Medical School, and HemOnc Today’s Multiple Myeloma Section Editor, and colleagues wrote. “These advancements have focused primarily on two drug classes: proteasome inhibitors and immunomodulatory drugs [IMiD]. Although these agents have contributed substantially to improved outcomes for patients with multiple myeloma, current therapies are not curative, and an unmet medical need exists for patients who progress following treatment.”
Paul G. Richardson, MD
The pan-deacetylase inhibitor panobinostat (Farydak, Novartis) affects the growth and survival of multiple myeloma cells.
Results of the phase 3 PANORAMA 1 trial showed the addition of panobinostat to bortezomib (Velcade; Millennium, Takeda Oncology) and dexamethasone significantly prolonged median PFS among patients with relapsed and refractory multiple myeloma (12 months vs. 8.1 months; P < .0001).
Richardson and colleagues conducted a subgroup analysis of this trial to evaluate the efficacy of the panobinostat regimen specifically in pretreated patients.
The analysis included data from patients previously treated with an IMiD (panobinostat, n = 245; placebo, n = 240), patients previously treated with bortezomib and an IMiD (panobinostat, n = 94; placebo, n = 99) and those treated with two or more prior lines of bortezomib and an IMiD (panobinostat, n = 73; placebo, n = 74).
PFS served as the primary endpoint.
The researchers observed a PFS increase with panobinostat across all subgroups.
Among patients previously treated with an IMiD, the researchers observed a median PFS increase of 4.9 months among patients treated with panobinostat vs. placebo (12.3 months vs. 7.4 months; HR = 0.54; 95% CI, 0.43-0.68).
Patients previously treated with bortezomib and an IMiD achieved a 5.8-month increase (10.6 months vs. 5.8 months; HR = 0.52; 95% CI, 0.36-0.76).
The largest median PFS increase occurred among patients who were heavily pretreated with bortezomib and an IMiD (12.5 months vs. 4.7 months; HR = 0.47; 95% CI, 0.31-0.72).
Commonly reported grade 3 and grade 4 adverse events associated with panobinostat across subgroups included diarrhea, neutropenia, thrombocytopenia, lymphopenia and fatigue.
Panobinostat appeared associated with a higher percentage of on-treatment deaths among patients previously treated with an IMiD (7.1% vs. 4.3%). However, the incidence of on-treatment deaths was similar in the remaining treatment subgroups, and there were no deaths due to disease progression attributed to panobinostat.
“These results provide guidance as to which patients may benefit more from the panobinostat-bortezomib-dexamethasone combination,” Richardson and colleagues wrote. “Investigation of other novel panobinostat combinations continue, including combinations with carfilzomib [Kyprolis; Onyx Pharmaceuticals, Amgen], ixazomib [Ninlaro, Takeda Oncology], and lenalidomide [Revlimid, Celgene], in order to identify new treatment alternatives for patients with limited options and provide insight on the safety profile of this novel agent.” – by Cameron Kelsall
Disclosure: Novartis funded this study. Richardson reports research funding from and/or advisory board positions with Celgene, Johnson & Johnson, Novartis and Takeda. Please see the full study for a list of all other researchers’ relevant financial disclosures.