The addition of the proteasome inhibitor Velcade® (bortezomib) to the treatment combination Revlimid® (lenalidomide) plus dexamethasone improves survival when used as initial therapy in multiple myeloma among patients who do not intend to immediately undergo a stem cell transplant according to clinical trial results published in The Lancet.
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.
A common standard treatment combination for newly diagnosed multiple myeloma includes Revlimid® and dexamethasone. Researchers continue to explore potential new combinations of therapies that improve outcomes for this group of patients.
Normal cellular processes include the breakdown of proteins that are no longer being used. The components of the protein that are broken down are then recycled into new, usable proteins. Proteasomes, structures found in healthy cells, play an important role in the breakdown and recycling of proteins.
Velcade® is a proteasome inhibitor, meaning it prevents proteasomes from breaking down unusable proteins in a cell. These proteins then start to accumulate within the cell, ultimately causing cellular death.
Researchers recently conducted a clinical trial to evaluate the effectiveness of Velcade in newly diagnosed multiple myeloma. The trial included 525 patients from 48 institutions: one group was treated with the addition of Velcade to Revlimid/dexamethasone, and the other group was treated with Revlimid/dexamethasone only, and results were directly compared. The patients in this trial had no intention of undergoing a subsequent stem cell transplant.
Researchers enrolled 471 eligible adult patients between February 2008 and February 2012 at 139 institutions throughout the National Cancer Trials Network. Patients ranged in age from 28 to 87, had active myeloma, and had not had a stem-cell transplant or any prior treatment for their disease. Patients were treated with a standard two-drug treatment consisting of Revlimid and dexamethasone for six cycles over six months or Revlimid, dexamethasone, and Velcade for eight cycles over six months and directly compared.
Patients receiving Velcade along with Revlimid and dexamethasone, in their first six months of treatment had a median remission time of 43 months compared to a median remission of 30 months for patients who received Revlimid and dexamethasone alone. Researchers also found that patients who received Velcade lived a median of 75 months, or about six years, after their initial treatment. Patients who received the standard two-drug treatment lived a median of 64 months, or about five years, after initial treatment.
Despite the increased remission and longevity, the three-drug combination did have a drawback: Patients who received Velcade were much more likely to experience sensory neuropathy, or tingling, pain, numbness or weakness in their hands and feet.
Durie, BGM, Hoering, A, Abidi, MH et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2016; (published online Dec 22.)[http://dx.doi.org/10.1016/S0140-6736(16)31594-X](http://dx.doi.org/10.1016/S0140-6736(16%2931594-X).
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