Multiple myeloma is a hematologic cancer that affects plasma cells, a type of white blood cell found in the bone marrow. These cells, normally involved in the production of antibodies, proliferate uncontrollably in myeloma, thus affecting the production of normal blood cells and weakening bones.

‍

Differences between myeloma and other blood cancers

Multiple myeloma is often compared to leukemias and lymphomas, but it has distinct characteristics :

• It touches plasma cells in the bone marrow (not white blood cells like leukemia).
• It does not form a single tumor but Spreads into several bones.
• Unlike lymphomas, it does not directly affect the lymph nodes.

The multiple myeloma is a heterogeneous disease that can be classified into several histological subtypes depending on the characteristics of immunoglobulins produced And tumor plasma cells.

1. Classification according to the type of immunoglobulin produced

Cancer plasma cells produce a monoclonal protein specific, which can be detected in blood or urine:

• IgG myeloma (the most frequent, about 50% of cases).
• IgA myeloma (20% of cases).
• Light chain myeloma (lambda or kappa, 15-20% of cases).
• IgD or IgE myeloma (rare, less than 2% of cases).
• Non-secreting myeloma (tumor plasma cells do not produce detectable proteins, approximately 1-2% of cases).

2. Specific variants of myeloma

Some forms of myeloma have specific characteristics:

• Solitary plasmacytoma : single plasma cell tumor, without diffuse medullary involvement.
• Indolent myeloma (asymptomatic) : presence of tumor plasma cells without symptoms or complications (fractures, renal failure, hypercalcemia).
• Plasma cell leukemia : aggressive form with the presence of tumor plasma cells circulating in the blood.

What are the biomarkers or genetic mutations involved in myelomas?

Les biomarkers and genetic mutations vary according to the subtypes of myeloma and make it possible to guide therapeutic strategies:

Myeloma with poor prognosis

• 17p deletion (TP53) : Associated with a resistance to standard treatments and to an aggressive evolution.
• t (4; 14) (FGFR3-MMSET) : Induces rapid proliferation of tumor plasma cells, often refractory to conventional therapies.
• Gain of 1q21 (+1q21) : Promotes tumor progression and decreases response to treatments.

Myeloma with better prognosis or therapeutic target

• t (11; 14) (CCND1-IGH) : Associated with a best prognosis, this mutation responds to BCL-2 inhibitors (venetoclax).

These genetic abnormalities play a key role in the prognosis and choice of treatments, allowing a personalized approach to multiple myeloma.

Unlike solid cancers that use TNM system, the multiple myeloma is classified according to biological, genetic and clinical criteria to assess the severity of the disease and adapt the treatment.

‍

La Salmon and Durie Classification, developed in 1975, is one of the first staging systems for multiple myeloma. This classification is based on clinical and biological parameters allowing to estimate The tumor mass of myeloma in the body.

She still remains used today, especially in specific contexts, although the new classifications are gradually replacing it.

‍

The International Staging System (ISS) was developed to improve the classification of multiple myeloma and refine the prognosis of patients. The ISS uses more accurate blood biomarkers to assess the severity of the disease.

The treatment of multiple myeloma depends on several factors: stage of the disease, Age of the patient, general condition and genetic factors. It is based on a combined approach including targeted treatments, chemotherapy, immunotherapy, and sometimes stem cell transplantation.

1. First-line treatment (newly diagnosed patient)

The initial treatment is aimed at reduce tumor burden and control symptoms.

a) Patients eligible for stem cell transplantation

For patients young people (< 70 years old) and healthy.

1. Induction treatment (reduction of the tumor before the transplant)
   • Standard triple therapy :
     • Proteasome inhibitor (ex: bortezomib).
     • Immunomodulatory (ex: lenalidomide or thalidomide).
     • Corticoid (ex: dexamethasone).
2. Autologous stem cell transplant
   
   • After chemotherapy at high doses (melphalan).
   • Enables prolonged remission.
3. Consolidation and maintenance treatment
   
   • Lenalidomide to maintain the response and delay relapses.

b) Patients not eligible for transplantation

For the older patients (> 70 years) or with comorbidities.

• Adapted triple therapy (bortezomib + lenalidomide + dexamethasone) or adapted chemotherapy.
• Maintenance treatment to prolong remission.

2. Treatment of relapses or refractory myeloma

When the disease recurs after initial treatment.

1. New targeted therapies
   
   • Ex: Daratumumab (anti-CD38 monoclonal antibody).
   • E.g.: Carfilzomib (proteasome inhibitor).
   • E.g.: Pomalidomide (immunomodulatory).
2. Catch-up chemotherapies
   
   • Association of new drugs to control relapse.

CAR-T cells and bispecific antibodies (new experimental approaches).

‍