Multiple myeloma: what treatment?

Multiple myeloma: a cancer of the bone marrow

By definition, multiple myeloma is a blood cancer. This is a very specific cancer of plasma cells, blood cells located in the bone marrow. Different treatments provide more or less heavy and effective treatment, depending on the severity of the disease and the patient’s state of health. A relatively rare disease, multiple myeloma represents 10% of hematological cancers.

Definition

Also known as Kahler’s disease, multiple myeloma is not one of the most common cancers but this disease is well known to hematologists. “It is a cancer of a specific blood cell, the plasma cell, which has the particularity of being located in the bone marrow.“, underlines Professor Steven Le Gouill, Professor in hematology and director of the Institut Curie. Plasma cells are very important cells of the immune system. They are part of white blood cells and have the function of making antibodies and preserving memory antigens throughout life, including memory of vaccination.

Each year, 5,500 new cases of multiple myeloma (or Kahler’s disease) are diagnosed, mainly affecting people over 70 years old, 3% of cases concern people under 40 years old.¹. “We have not identified any predisposing genetic or family background. Epidemiological studies in the USA show more cases in the African-American population. We are seeing more cases among farmers and people who have been exposed to ionizing radiation or pesticides“, explains Professor Steven Le Gouill.

Kahler’s disease: Causes and progression

Located mainly in the bone marrow, the tissue contained in the bones where all blood cells are produced, the plasma cell comes from B lymphocytes and has the function of producing antibodies, immunoglobulins. When the cell becomes diseased, manufacturing anomalies appear. “An abnormal production of antibodies can be observed during a blood test or electrophoresis. This is called monoclonal gammopathy of undetermined significance (MGUS).“, explains Professor Steven Le Gouill.

MGUS may remain stable for an indefinite period and never progress to myeloma. The risk of developing cancer is in fact very low, around 1%. However, it is important to carry out regular monitoring by means of an annual blood test. The transition from MGUS to the myeloma stage results in various clinical signs that must quickly be taken into consideration.

What are the symptoms of multiple myeloma?

These signs are grouped under the name CRAB: C (hypercalcemia), R (renal failure), A (anemia), B (bones, bone lesions), as specified by the National Cancer Institute:

• Hypercalcemia, that is to say an abnormally high quantity of calcium circulating in the blood;
• Renal failure, in other words a dysfunction of the kidneys which no longer do their job of purifying the body properly;
• Anemia, i.e. a decrease in the level of hemoglobin in the blood;
• One or more bone lesions, that is to say lesions in the tissue that makes up the bones (bone tissue). These bone lesions are also called lytic lesions or osteolytic lesions. They manifest in particular by bone pain and spontaneous fractures.

“As the plasma cell is located in the bone marrow, cellular abnormalities will result in bone lesions.“, explains the Professor in hematology. Fractures and collapse of the spine, including during simple actions of daily life, can then occur. The proliferation of plasma cells invades the bone marrow at the expense of other blood cells.”Abnormalities in plasma cells can disrupt the production of red blood cells and lead to anemia or even kidney damage.“, continues the specialist. However, it is rare for all the signs of CRAB to be present at the same time in the same person.

Myeloma can also be mentioned in the face of repeated infections (pulmonary, ENT, etc.) which reflect a decline in immune defenses.

Finally, it can be discovered as part of a health check, blood test (for example, by an acceleration of the sedimentation rate) or imaging, etc. It can also be discovered during the follow-up of an MGUS.

“There is a great diversity of clinical pictures depending on the patient. It’s really very heterogeneous“, points out Professor Steven Le Gouill.

From symptoms to diagnosis of multiple myeloma

Multiple myeloma is not necessarily associated with symptoms during the early stages of the disease. The signs appear when the tumor has grown into the bone marrow. Other repercussions may occur if immunoglobulins accumulate in organs such as the kidney.

How is multiple myeloma diagnosed?

The diagnosis of multiple myeloma is based on a variety of medical tests. A blood test is necessary, including a hemogram (analysis of blood cells) as well as urine tests. Furthermore, protein electrophoresis as well as a myelogram (bone marrow sample), generally carried out at the level of the sternum bone, must also be considered. “A pet scan and other medical imaging analyzes make it possible to classify myeloma and map the disease. It is essential to have a complete diagnosis of myeloma“, specifies the Professor in hematology.

A combination of different possible treatments

Whether self-transplanted or not, patients all receive a combination of targeted therapies. “Autograft is always preceded and followed by a treatment phase with targeted therapies, as maintenance treatment., specifies Professor le Gouill. If the age limit for benefiting from an auto-graft of hematopoietic stem cells is generally set at 65 years, this limit is not strict and depends above all on the state of health of the patient.

Appearing in the 2000s, targeted therapies consist of alkylating agents, proteasome inhibitors, immunomodulators as well as monoclonal antibodies (anti CD38). They are often associated with steroids which have not only analgesic, but also anti-tumor action.

Patients may also receive symptomatic treatments. “We can use opioids and/or analgesics for pain and EPO to combat anemia. continues the Professor in hematology. Some patients also receive preventive antibiotic treatments against infections. “Furthermore, bisphosphonates can also be administered to prevent worsening of bone lesions. All these medications are supportive treatments. explains Professor le Gouill.

Treatment of multiple myeloma: major advances

If myeloma could be considered a fatal disease until the mid-1990s, major therapeutic advances have significantly changed the prognosis of this disease. “It is a disease which has experienced a real therapeutic revolution thanks to the arrival of innovative treatments in the space of 20 years, in particular thanks to the work of the teams of researchers from the Intergroupe Francophone du Myeloma“, recalls the specialist².

Thus, in the mid-1990s, auto-stem cell transplants considerably improved the management of multiple myeloma. More recently, the arrival of other drug classes (immunomodulators, targeted therapies, Cart T Cells, etc.) have also played a major role in the treatment of multiple myeloma as well as in the understanding of the disease.

The response to treatments, however, remains variable depending on the patient’s general health, their age and the type of myeloma, with certain forms remaining very aggressive, causing relapses and reducing the chances of remission.