Multiple myeloma
A stubborn blood cancer, but there is hope
Derived from the Greek words for “marrow” and “tumor,” multiple myeloma is an incurable blood cancer first reported in a woman in England in 1845. Interestingly, it is also found in cats, dogs and horses.It now affects almost 500,000 people around the world, including 6.5 people per 100,000 in the US. About 500 Israelis were diagnosed with it last year, among a total of between 2,000 to 3,000 being treated for it here.
As it almost never affects people before their 60th birthday, it is a disease of the elderly; with the aging of the world population, the numbers of patients are expected to grow. The lifetime risk of contracting it at some point in one’s lifetime is 0.7%. Multiple myeloma is the second-most-common blood cancer (10%) after non-Hodgkin’s lymphoma, representing about 1.8% of all new cancers and causing 2.1% of all cancer deaths.
If the patient goes untreated, he will usually die within seven months to a year; if he does get suitable care, survival – but often an unpleasant quality of life – persists for about four or five years.
One of the world’s leading experts in the disease is Prof. Thierry Facon, a senior hematologist at Lille University Hospital; he received his medical degree at Lille University School of Medicine in 1987 and quickly became assistant professor of hematology at the large, 3,500-bed hospital, where his hematology department has 75 beds.
“My parents and siblings were not in medicine, but one of my sons is a fellow in surgery. My father was a general in the French army, and there are several military officers in the family. One of my brothers is based in Russia working for an oil company, while another is in the movie industry in Canada. When I was very young,” Facon recalled, “I said I wanted to be a doctor. It’s hard to say why. I started studying it in 1977, and I am very happy with my career choice. Why hematology? As a medical student, I spent time at the hematology department, and the people I met were very kind and a good team.”Lille was a coal-mining and textile-industry city in the past, but today it has many fewer factories – mostly businesses but not much hi-tech. “Our Eurostar train easily reaches Paris and London, so that is good for business.”
Facon, who was recently a guest of Neopharm Pharmaceuticals in Israel, was president of the French Intergroup on Myeloma between 2003 and 2006, vice president of the French Society of Hematology between 2005 and 2013 and a regular presenter at medical meetings on advances in coping with the disease. The physician is a member of the American Society of Hematology, the International Myeloma Working Group and the International Myeloma Foundation and his research has appeared in leading medical journals. During his fifth visit to Israel since 2008, he lectured on the subject during his brief, twoday visit at Tel Aviv Sourasky Medical Center, Rambam Medical Center in Haifa and Hadassah University Medical Center in Jerusalem. MORE THAN 170 years after the first patient was diagnosed, the cause of multiple myeloma – also referred to as plasma cell myeloma –-is still unknown, but risk factors and the mechanism of the disease have been identified.
It is a malignancy of plasma cells, a type of white blood cell responsible for producing antibodies. It begins when abnormal plasma cells produce abnormal antibodies that harm the kidneys and cause the blood to be too thick. The plasma cells also accumulate in the bone marrow or soft tissue. In the bone marrow, myeloma cells crowd out healthy white and red blood cells, causing tiredness and weakening the immune system’s ability to fight infections.
At first, the patient does not notice any symptoms, said Facon in an interview with The Jerusalem Post. Early signs include bone pain, mostly in the spine or chest), constipation, nausea, lack of appetite, confusion, tiredness, loss of weight, excessive thirst and weakness or numbness in the legs.
But gradually, bleeding, anemia, significant bone pain and frequent infections appear. Accumulations of amyloid plaque and high levels of calcium in the blood may occur as the disease progresses.
The disease is slightly more prevalent in men than in women. Other risk factors besides this and age may include drinking too much alcohol.
“The environment has been implicated in the disease. We have seen a higher risk in patients exposed to industrial compounds and agricultural pesticide, but environmental influences are behind many other cancers as well,” said the French physician. “Epidemiologists who have studied myeloma for many years have found that exposure to radiation is a risk factor. Doctors who pioneered the use of radiology were not very well protected in the 1950s and were exposed to too much radiation, which is theoretically a risk factor. Air pollution might be involved as well.”
There may be a familial risk, but children usually don’t have to worry about eventually getting multiple myeloma if a parent contracted it. But, said Facon, “if you look at families, often there is more than one patient with hematological diseases. The disease has no autoimmune connection.”In younger patients, the median survival is seven to 10 years. We have made a lot of progress with the disease in the last 15 years. When I started to study hematology, most lived for less than 13 months after diagnosis. We have very few patients younger than 45. But it isn’t an easier disease when patients are young. It’s not a good disease for patients. Most of them suffer from a compromised quality of life. About 80% of them have symptoms. In a small minority,-there are no symptoms when patients are diagnosed by chance. Asymptomatic patients are not treated, but every patient without symptoms eventually does show symptoms within two years
When patients complain about symptoms, they are usually sent for urine or blood tests that show abnormal antibodies and then bone marrow biopsies that find cancerous plasma cells. WORKING WITH cancer patients is “very difficult. Some doctors wouldn’t be able to work in cancer wards because of the deaths. The recovery and cure rate in children is high, but I work only with adults. My university hospital keeps hemato-oncology departments for adults and children completely separate. It’s not a good idea to have children and adult blood cancer patients together. In France, they are always separate,” he said, when told about the imbroglio at Hadassah University Medical Center in Jerusalem, where six senior hemato-oncologists resigned in June, claiming that Hadassah Medical Organization management wanted to unite the departments there to save money.As for other complaints by the resigning doctors that HMO took in medical tourists from abroad who wanted treatment, Facon noted: “At our hospital, there as a major discussion about taking blood cancer patients from the United Arab Emirates, but we decided not to do this at the expense of French patients. WHILE NOT yet curable, multiple myeloma is considered treatable. Among the treatments considered for younger patients are autologous stem-cell transplants (up to two in each patient) and giving chemotherapy and the drugs thalidomide or a variant called lenalidomide in older ones.
Thalidomide, which was notorious for decades since the 1960s, is well known to the layman because it caused severe defects in children. The drug was regarded as “safe as aspirin” and widely prescribed as a sleeping pill and tranquilizer, but when taken by pregnant women, it resulted in the birth of many children who lacked limbs and had what looked like flippers instead. By the end of 1962, it was banned in most countries.But thalidomide, said Facon, was “rediscovered – by chance – by a US physician for myeloma in 1998. Prof. Yehuda Folkman, a leading researcher in angiogenesis (the development of new blood vessels) and physician at Harvard Medical School who died nine years ago, suggested thalidomide for the disease. The treatment was approved for men and women (but not those younger women who could become pregnant). The rules on use are very strict, and it is prescribed with much caution.
Then a US company named Celgene (represented in Israel by Neopharm) created a new but related compound that has been shown more effective than other drugs for multiple myeloma.
“We may get new agents of this drug family for this cancer in next few years,” said Facun.
As immunomodulatory agents, Celgene’s drugs can directly kill myeloma cells and modify environments, improving the immune system to a certain extent. Often, a “cocktail” of these drugs work with improved efficacy for a synergistic effect, he said.
The drugs are not yet used as “front-line” medications, but for maintenance, including after a stem-cell transplant.
“If these drugs are not used for maintenance, the next progression will occur within two years. If the patient gets a maintenance drug, the disease can progress in four years. But it’s not a cure. Still, myeloma experts are now talking about an eventual cure for younger patients who get access in the future to new drugs.”
In 2013, the European Commission (which approves drugs in European countries) allowed the combinational therapy of pomalidomide, known in the US as Pomalyst, and dexamethasone for treating patients with relapsed and refractory (persistent or unmanageable) multiple myeloma who have received a minimum of two prior therapies. Thalomid (thalidomide) was previously approved by the US Food and Drug Administration and the EU for newly diagnosed patients, and Revlimid (lenalidomide) was okayed for patients who had already been given one drug. Pomalyst (pomalidomide) was approved in the US and the EU for relapsed and refractory patients who had already been treated with two drugs. Revlimid (lenalidomide) is waiting approval for newly diagnosed and maintenance patients. All of these are made by Celgene, but other drugs such as Velcade and the Israeli-developed Doxil – from different pharmaceutical companies – are also prescribed for multiple myeloma. Even though these drugs do not yet constitute a cure, Facon believes that there is hope.
“I think that within few years, there will be a cure for multiple myeloma,” he concluded.