Stem Cell Transplants for Multiple Myeloma:
Is it Right for Me?
Multiple myeloma is a blood cancer that affects plasma cells. Plasma cells are bone marrow cells that normally make antibodies which fight infection.
In patients with myeloma, the plasma cells become malignant, causing the cells to grow uncontrollably and overpopulate the bone marrow. 
Edna Carter
The cause of multiple myeloma is unknown. The risk of developing myeloma increases with age; approximately 85 percent of patients are over age 55. It is more common in men than in women, and in African Americans than in Caucasians.
For years, few therapies showed promise for myeloma patients. But in the last ten years a new group of drugs to treat multiple myeloma have significantly prolonged survival for multiple myeloma patients. These drugs –Thalomid® (thalidomide), Revlimid® (lenalidomide) and Velcade® (bortezomib) – are often referred to as “the novel agents” and are now a standard part of most initial myeloma therapies, as well when patients relapse.
But what happens after patients complete their initial treatment? Should they wait and see what happens or consider a stem cell transplant?
Autologous Stem Cell Transplants
Autologous stem cell transplantation is as an important option for the treatment of multiple myeloma patients. More autologous transplants are performed in patients with multiple myeloma each year than any other disease.
“Autologous transplants have a low mortality rate, high response rate and prolong the period of remission in many patients,” says David H. Vesole MD PhD, a myeloma specialist at Loyola University Medical Center in Maywood IL. “What’s more, it can be used to treat patients even in their 70’s.”
The best candidates for an autologous transplant are those who are generally in good health and do not have kidney, lung or heart problems, says Vesole. “They should also have responded to prior chemotherapy treatment.”
Patients who benefit least are those with a very aggressive form of multiple myeloma, and who have high LDH, beta-2-microglobulin levels (measured in the blood) or those who do not respond to therapy.
Prior to an autologous stem cell transplant, the patient’s blood stem cells are moved from the bone marrow into the blood stream. This is done using injections of Neopogen®, Neupogen® plus Cytoxan® or Neupogen® plus a new drug called Mobozil®. The stem cells are then collected from the blood stream in a procedure called a stem cell harvest. The blood is withdrawn from the patient, and passed through a machine that separates out the stem cells, and returns the rest of the blood to the patient. The stem cells are frozen until it’s time for the transplant.
After the patient undergoes high dose chemotherapy, the thawed stem cells are infused back into the patient’s blood stream, much like a blood transfusion. The stem cells find their way to the bone marrow, where they begin producing healthy new blood cells.
“Giving eligible patients a combination of the novel drugs plus dexamethasone, followed by a stem cell transplant, provides superior results,” says Vesole. “Nearly all patients respond to the therapy, and a substantial percentage achieve a complete or very good partial remission.”
As with most cancer fighting drugs, these drugs have some side effects. Thalidomid® may cause tingling and numbness or a burning sensation in the hands and feet. Less often, it can cause blood clots. Revlimid® occasionally causes blood clots and low blood counts. Velcade® can also cause tingling and numbness in hands and feet.
At some centers, patients undergo a tandem transplant, which is two autologous transplants, one after the other. Several studies have shown that tandem transplants control the disease longer than a single transplant.
However, Jayesh Mehta MD, a myeloma specialist at Northwestern University Cancer Center, cautions that this may be true for only a subset of patients. “The studies suggest that patients who have a complete or very good partial remission after the first transplant benefit less from a second transplant than those who do not achieve at least a very good partial remission,” says Mehta.
When to Transplant
Experts disagree on when to transplant patients with myeloma. Given the success of the “novel agents” in managing myeloma, some suggest waiting until the disease begins to progress before initiating a transplant. Others, like Mehta, disagree.
“The evidence shows that patients who undergo an autologous transplant early in the course of their disease have more time without myeloma symptoms and, thus, a better quality of life,” he says. He also cautions that the data is limited on how long novel agents alone will prolong survival, or what the effects are of prolonged use.
“We do know that the novel agents work well after an autologous transplant,” says Mehta.
Donor Transplant
Another option for patients with multiple myeloma is an allogeneic transplant which uses stem cells from a donor, instead of the patient’s own stem cells. The advantages of an allogeneic transplant are that the donor’s immune cells can help eliminate myeloma cells, and when successful, it can prolong survival or even cure some patients.
But Mehta cautions that the risks are much greater with an allogeneic transplant than with an autologous transplant. “Patients have a greater risk of developing serious complications, such as graft-versus-host disease, that can compromise their quality of life or be fatal,” he explains. “Nonetheless, it is a useful tool for a subset of patients.”
Unanswered Questions
Researchers are still working to clarify many unanswered questions. “One thing is clear,” says Vesole. “Survival rates have steadily improved since the introduction of Thalomid®, Revlimid® and Velcade® and the use of autologous stem cell transplants to treat myeloma patients. We now have several powerful tools at our disposal to help myeloma patients lead a longer and healthier life.”
Webcast
You can view new webcasts on multple myeloma that discuss the issues associated with transplant in greater detail. Understanding Myeloma
Transplants for Myeloma: Is it right for Me?
Thanks to Celgene and Millenium Pharmaceuticals who made these webcasts possible.
   
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