Drug Extends Survival for Multiple Myeloma Patients
WEDNESDAY, June 15 (HealthDay News) -- The largest study of its kind has confirmed the effectiveness of the drug Velcade in holding back disease progression after relapse in patients with the deadly blood cancer multiple myeloma.
Patients looking for a new therapeutic option fared significantly better on Velcade (bortezomib) than on the standard therapy, high-dose dexamethasone, according to a report in the June 16 issue of the New England Journal of Medicine.
Overall, 80 percent of those taking Velcade were still alive one year later, compared to 66 percent of those prescribed dexamethasone.
"It's the arrival of new therapies like Velcade that we hope can really have a big impact on long-term survival," said lead researcher Dr. Paul Richardson. He is an assistant professor of medicine at Harvard Medical School and clinical director of the Jerome Lipper Multiple Myeloma Center, part of the Dana Farber Cancer Institute in Boston.
Even in the world of blood cancers, multiple myeloma is a particularly lethal disease, claiming the lives of more than 11,000 Americans each year.
"It [multiple myeloma] arises from plasma B-cells, cells that give us the ability to produce antibodies that fight off infection," Richardson explained. B-cells reside primarily in bone marrow.
"Multiple myeloma is the most malignant transformation of those plasma cells into a tumor that dominates the marrow, causing very painful bony lesions that can damage the kidneys through an excess production of protein," he added. "It also increases the likelihood of infection, which is often deadly."
According to Richardson, "median survival used to be just two or three years, but the advent of bone marrow transplant has improved outcomes to about five years."
Relapse is common, however.
"At that point, high-dose dexamethasone has been the standard therapy," said Louis DeGenarro, vice president of research at the Leukemia & Lymphoma Society. "To be honest, there just aren't many choices for these patients."
Based on promising results from a preliminary trials conducted a few years ago, the FDA has already approved the use of Velcade for relapsed multiple myeloma patients -- on the condition that a large, controlled study be conducted to confirm those findings. Richardson's group of North American and European researchers have now completed that trial.
They tested Velcade against high-dose dexamethasone in 669 patients whose cancer had returned after the completion of between one to three previous treatments. Participants received either intravenous Velcade or high-dose dexamethasone for approximately 40 weeks.
Velcade did improve survival, the researchers report. A total of 38 percent of patients using the drug experienced either a complete or partial response in terms of cancer remission, compared to 18 percent of those taking dexamethasone. Six percent of Velcade users achieved a complete response, compared to just 1 percent of those on standard therapy, the researchers added.
Average time to disease progression -- when signs of cancer reappeared -- was just over six months for those on Velcade vs. 3.5 months for those taking dexamethasone, meaning that "you've doubled your time of disease control," Richardson said.
The study was funded by Millenium Pharmaceuticals, the makers of Velcade.
The drug works by blocking the activity of the proteasome, a key structure that regulates how cells recover from injury, grow and divide. "If you block that mechanism, you can then trigger a whole series of downstream events that end up killing the myeloma cells," Richardson explained.
Side effects were roughly similar between the two drugs, with Velcade showing a slightly higher rate of more onerous side effects. Richardson characterized Velcade's side effect profile as "manageable," however.
DeGennaro said he "applauded" the quality of the research, but added that it marks an "incremental advance" in terms of multiple myeloma treatment. "It offers an alternative to high-dose dexamethasone, and it's certainly in the right direction," he said.
Dr. Angela Dispenzieri is an assistant professor in the division of hematology at the Mayo Clinic and co-author of a journal commentary on the study. She agreed that while Velcade isn't a cure, "we'll take everything we can get -- it all adds up for our patients."
The experts agreed that a real cure for multiple myeloma will rely on a much better understanding of its underlying causes.
"Unfortunately, it's a very heterogenous disease, it could be dozens of diseases just lumped under one title," Dispenzieri said. "We simply don't understand all the triggers for this cancer, and that makes it much harder -- it's a moving target."
She said Velcade could replace dexamethasone as the "first-line" drug for patients with relapsed multiple myeloma, and noted that there is also "a lot of work in using this drug in combination with other drugs."
One barrier to widespread use is cost, however. Dispenzieri calculated the price tag of a nine-month supply of Velcade at nearly $46,000 -- compared to just $170 for dexamethasone over the same period of time. Luckily, because Velcade is administered intravenously, Medicare would cover that expense for many patients.
"Other drugs that have proven effective, such as thalidomide, come in a pill -- and that's not covered under current Medicare rules," she said. "So these drugs [like thalidomide] can be advances, but then they are just out of patients' range because they are too expensive and they just aren't covered."
These types of financial concerns can play a big role in treatment decisions, Dispenzieri noted.
"Sometimes I have a conversation with patients -- 'Well, I can give you thalidomide or Velcade -- what's your insurance like?' Not, 'What's the better medical decision for you?' That's the reality, unfortunately."
To learn more about myeloma, visit the Leukemia & Lymphoma Society.