Farydak® Significantly Improves Outcomes for Heavily Pre-Treated Multiple Myeloma

The addition of Farydak® (panobinostat) to the standard treatment combination consisting of Velcade® (bortezomib) and dexamethasone significantly improves progression-free survival among patients with advanced multiple myeloma who have stopped responding to prior therapies.

Importantly, the addition of panobinostat provided the greatest improvements among patients who had received two or more prior therapies. These results were recently published in the journal Blood.

Multiple myeloma is a type of blood cancer that affects certain immune cells called plasma cells. Healthy plasma cells produce proteins called antibodies that are an important part of the immune system’s defense for fighting bacteria and viruses.

Cancerous plasma cells tend to replicate at a fast pace, crowding out other healthy immune cells, as well as producing malfunctioning antibodies. These antibodies tend to cause damage to the kidneys, in addition to reducing the immune system’s ability to efficiently fight infection.

Researchers continue to evaluate novel treatment options for multiple myeloma, particularly among patients whose disease has progressed despite prior therapies. Novel therapeutic agents that do not tend to create the severity of side effects associated with chemotherapy continue to be developed for the treatment of various types of cancers, including multiple myeloma. Studies are ongoing to explore optimal combinations and sequences of regimens containing these novel compounds.

Farydak is an agent that belongs to a class of drugs called deacetylase (DAC) inhibitors. It creates its anti-cancer effects through disrupting the mechanisms of several enzymes within a cell that are integral to cell survival. The DAC inhibitors have demonstrated improved anti-cancer activity if they are used in combination with a class of agents called proteasome inhibitors, such as bortezomib and Kyrpolis® (carfilzomib).

Panobinostat was approved by the United States Food and Drug Administration (FDA) in February, 2015, for the treatment of multiple myeloma, in combination with bortezomib and dexamethasone, among patients who had received at least two prior therapies.

The two prior therapies must have included bortezomib and at least one treatment including an immunomodulatory drug (IMiD). Agents approved for the treatment of myeloma that are in the IMiD class include Revlimid® (levalidomide), Thalomid® (thalidomide), and Pomalyst® (pomalidomide).

Researchers recently conducted a subgroup analysis to determine if there were differences in outcomes based on prior therapies among patients with multiple myeloma treated with panobinostat.

The analysis was conducted from data obtained from the clinical trial prompting the approval of panobinostat, called the PANORAMA 1 trial. The PANORAMA 1 trial included multiple myeloma patients whose cancer had progressed despite prior therapy.

Patients in the trial were treated with either panobinostat plus bortezomib/dexamethasone, or placebo (inactive substitute) and bortezomib/dexamethasone. Outcomes between the two groups of patients were directly compared.

The main outcome assessed was median progression-free survival (PFS), or the median time from treatment delivered during the trial to cancer progression among surviving patients.

  • Among patients who had received therapy with an IMiD prior to the trial, median PFS was 12.3 months for those treated with the addition of panobinostat to bortezomib/dexamethasone, compared with 7.4 months for those treated with placebo/bortezomib/dexamethasone.
  • Among patients who had received therapy prior to the trial with bortezomib plus an IMiD, median PFS was 10.6 months for those treated with the addition of panobinostat to bortezomib/dexamethasone, compared with 5.8 months for those treated with placebo/bortezomib/dexamethasone.
  • Among patients who had received therapy prior to the trial with two or more regimens, including an IMiD and bortezomib, median PFS was 12.5 months for those treated with the addition of panobinostat to bortezomib/dexamethasone, compared with 4.7 months for those treated with placebo/bortezomib/dexamethasone.
  • Severe side effects were similar regardless of the number of therapies patients had received prior to the trial.

The researchers concluded that “This analysis demonstrated a clear PFS benefit of 7.8 months with [panobinostat/bortezomib/dexamethasone] among patients who received ≥2 prior regimens including bortezomib and an IMiD, a population with limited treatment options and poorer prognosis.”

Patients with multiple myeloma who have received extensive prior therapy should speak with their physician regarding their individual risks and benefits of treatment including panobinostat.

Reference: Richardson P, Hungria V, Yoon S-S, et al. Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: outcomes by prior treatment. Blood. 2016;127(6): 713-721. DOI: http://dx.doi.org/10.1182/blood-2015-09-665018. Available at: http://www.bloodjournal.org/content/127/6/713?sso-checked=true. Accessed February 17, 2016.

 

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