Multiple myeloma: a disease of the bone marrow
Myeloma, or Kahler’s diseaseis a bone marrow cancer linked to an abnormal proliferation of particular cells, the plasma cells. About 6,000 new cases are diagnosed each year in France. The patients have an average age of 70 years.
At present, scientists do not know how to explain why plasma cells become cancerous. But the mechanism of the disease and its consequences on patients are well identified.
Where is the bone marrow located?
Bone marrow is a substance found in the bones, mainly in the ribs, vertebrae and pelvis. Its role is to make hematopoietic stem cells which, in turn, will give rise to blood cells: red blood cells, white blood cells (including plasma cells) and platelets.
What are plasma cells in the blood for?
Plasma cells that proliferate abnormally in multiple myeloma usually produce antibodies, the immunoglobulins. When the disease sets in, “the proliferating plasma cells will secrete immunoglobulins but which have no antibody activity”, explains Prof. Philippe Moreau, hematologist at the Nantes University Hospital and president of the French-speaking Myeloma Intergroup. For the patient, this dysfunction will lead to a whole cascade of consequences.
What are the symptoms of multiple myeloma?
The disease sets in gradually without giving any particular symptoms in its early stages. Most often, blood abnormalities are discovered by chance during a blood test or examination called electrophoresis serum proteins. When this electrophoresis reveals an abnormal peak of monoclonal immunoglobins, we speak of monoclonal gammopathy of undetermined significance (GMSI or MGUS in English). “This monoclonal peak on electrophoresis may be trivial. It may simply be related to aging. It does not mean that the patient will develop multiple myeloma. This is only the case in 1 out of 100 cases. explains Professor Moreau.
In this situation of GMSI, the myeloma remains “indolent”, that is to say without clinical signs and the person is placed under surveillance, without any particular treatment. Follow-up consists of one electrophoresis per year. The doctor also monitors the possible appearance of bone pain or anemia.
What symptoms when myeloma becomes active?
At a certain stage, myeloma gives – as its name suggests – multiple symptoms.
The first symptoms of myeloma
- bone pain are the first symptoms of myeloma. They are mainly located in the back or pelvis. “These pains are intense and resistant to simple analgesics”, specifies the hematologist. They are explained by the disturbed functioning of cancerous plasma cells which begin to secrete bone resorption factors. Over time, the bone becomes brittle, exposing the patient to vertebral compression or fractures.
- Anemia is very common. As tumor plasma cells destroy red blood cell precursors, the red blood cell count falls to an abnormally low level.
- Hypercalcemia, another typical symptom, is related to bone resorption. By destroying itself, the bone releases calcium into the blood, hence the abnormally high level. This anomaly can lead to severe fatigue, dehydration or neurological disorders.
- kidney failure is also present in multiple myeloma. It is caused by the buildup of abnormal proteins in the kidneys, preventing them from functioning normally.
- Repeated infections finally characterize multiple myeloma. This is easy to understand since plasma cells, cells involved in the immune system, do not function normally.
Multiple myeloma: which risk factors?
Since 2015, multiple myeloma has been recognized as occupational disease among farmers and employees called upon to handle pesticidesprovided they have been exposed to it for more than 10 years.
Much rarer, accidental exposure to ionizing radiation, at high doses, also increases the risk of myeloma.
Myeloma: how to detect bone marrow cancer?
Indispensable examination, the myelogram is made from a bone marrow puncture. “We aspirate bone marrow to count the plasma cells. The diagnosis of multiple myeloma is made when more than 20% of abnormal plasma cells are found. These plasma cells are also sorted in the laboratory looking for specific chromosomal abnormalities, some of which have a poorer prognosis. About a third of patients have these abnormalities,” explains Professor Moreau.
The scanner where the Pet-Scanimaging examinations, make it possible to look for possible bone lesions.
The results of the electrophoresis and a blood test (calcaemia, renal function, anemia, etc.) complete the picture necessary for the diagnosis of myeloma.
How to treat multiple myeloma?
The treatment is adjusted according to the patient’s age and general condition. In the field of multiple myeloma, research is progressing rapidlywith such good results that “our treatment recommendations change every two years”, rejoices the hematologist. The general idea now is to combine several types of drugs to attack cancer cells from different angles.
Multiple myeloma: the treatment for the youngest patients
Autologous hematopoietic stem cell transplantation allows the use of intensive chemotherapy. Drugs like melphalan are given in high doses. This “chemo” kills cancer cells, but also normal cells. To allow the patient to support this protocol, his own stem cells are collected preventively, and then reinjected. This autograft is only possible in patients under 65 years old, maximum 70 years old.
Cellular immunotherapies increase in multiple myeloma. Hope lies in particular in the injection of Cart-T cells (the patient’s own lymphocytes, genetically modified and reinjected). “But we have very little access to this treatment currently in France”, regrets Professor Moreau.
Targeted therapies appeal to monoclonal antibodies, the aim being to aim at a target on the surface of the tumor cell, in order to destroy it. Prof. Moreau’s team has taken part in clinical trials on the teclistamab, a “bispecific” synthetic antibody (source 1). Part of this antibody binds to an antigen specific to tumor cells, BCMA. The other part binds to certain T lymphocytes (cells of the immune system called CD3) which will then approach the cancerous cell and destroy it. “It’s a revolution! », says Professor Moreau. Teclistamab is administered by subcutaneous injection once a week. The response rate is 65%.
Teclistamab received its European marketing authorization in August 2022. For the time being, it is reserved for patients in therapeutic impasse. “We hope in the future to administer it to patients at an earlier stage of the disease, in combination with other drugs. From this year 2023, we will also test it on the front line, as soon as the diagnosis is announced.”explains the hematologist.
Apart from teclistamab, other bispecific antibodies will arrive on the market, each with different targets. Hence the interest of combining them to improve the response to treatment.
Multiple myeloma: treatment for older patients:
A combination of three drugs, lenalidomide, dexamethasone (cortisone) and daratumumab (a monoclonal antibody) is proposed. “The response rate is 90% and is maintained on average for five years. If myeloma relapses, we have other drugs to offer,” explains the hematologist.
Can multiple myeloma be cured?
Myeloma remains an incurable disease but, thanks to recent therapeutic advances, thelife expectancy of patients has clearly lengthened.
What is the life expectancy with multiple myeloma?
“Thirty years ago, when I started working on multiple myeloma, patient survival was two or three years. Today, we reach 10 years”, observes Professor Moreau.
Myeloma: a possible cure?
Healing becomes possible for the youngest patients, that is to say less than 70 years old. Thanks to new therapeutic strategies, “We can cure 10% of myelomas. Within five years, we hope to cure one out of two patients among patients who do not present poor prognostic factors”, ensures the hematologist.
To know : there are patients and their families who can find help from Af3m, the French association for patients with multiple myeloma.
