Multiple myeloma treatments

Not every diagnosed myeloma requires treatment. In patients whose disease is detected early or who do not present criteria involving treatment (CRAB or SLiM CRAB criteria), simple monitoring is proposed. Myeloma is then said to be indolent. 

For other patients, the treatment is based on a combination of several therapeutic classes (immunotherapy, targeted therapy, chemotherapy, etc.) for a synergistic effect. They are selected according to the characteristics of the patient and their history. 

The prognosis of multiple myeloma has undergone a significant change over the last ten years. Different possible lines of treatment, based on innovative therapies, have led to the disease becoming chronic. Survival has thus increased considerably, even if the disease remains incurable. 

The management of patients with multiple myeloma is expected to improve further, while new therapies are being evaluated in the context of national clinical trials carried out at Institut Curie and managed by the IFM (French-Speaking Myeloma Intergroup).

Chemotherapy for multiple myeloma 

Chemotherapy is used less and less to fight multiple myeloma, at least as a stand-alone treatment, and instead immunotherapies and targeted therapies are favored. The treatment is in fact based on combinations of several molecules. 

Conventionally, in younger patients (under 65 years old), stem cell transplants, called autografts, are performed, preceded by intensive chemotherapy. 

The standard procedure for younger patients involves six courses of induction by immunology and targeted therapy, called Dara-VRd, combining daratumumab (Dara), bortezomib (V), lenalidomide (R) and dexamethasone (d). This treatment is followed by intensive chemotherapy and an autograft of bone marrow. It is then followed by two consolidation treatments and maintenance treatment with an immunomodulator or imid. 

On the other hand, in patients over 65 years of age, autografting presents too many risks. This is why a combination of immunotherapy and targeted therapy is generally administered as first line treatment.

Immunotherapy for multiple myeloma

Among the new therapies for multiple myeloma, there are molecules that act on the immune system, such as the monoclonal antibody daratumumab, targeting a small molecule on the surface of abnormal plasma cells called CD38. 

Isatuximab is another effective monoclonal antibody that targets myeloma cells also expressing the CD38 antigen on their surface. 

Immunomodulators of the imid family, such as revlimid or pomalidomide, which have a direct anti-tumor effect, are also used to manage multiple myeloma. 

Finally, in the case of myeloma recurrence, new immunotherapy agents are now used, such as bispecifics. For example, teclistamab and elranatamab have recently obtained marketing authorization and may be indicated to activate the immune system.

Targeted therapy for multiple myeloma

In targeted therapy, certain drugs make it possible to inhibit the proteasome, responsible for the degradation of cellular proteins, which is a regulator of growth and programmed cell death (apoptosis). They thus lead to a blockage of tumor cells in the cell cycle and a reduction in their proliferation. Among the proteasome inhibitors, bortezomib and carfilzomib are used to fight myeloma. 

Finally, a new therapy based on the CAR-T cell technique (chimeric antigen receptor) promises to be particularly effective for patients with multiple myeloma. This treatment consists of reprogramming the immune cells of the patients, so that they specifically recognize the cancer cells and destroy them. Institut Curie is a pioneer in the development of these forms of cell and gene therapies against cancers. 

Institut Curie is home to the CellAction (Cell Therapy Acceleration and Innovation) platform, which is integrated into the Paris-Saclay Cancer Cluster (PSCC) and which offers numerous medical-scientific expertise and cutting-edge equipment. It is dedicated to developing these forms of cell and gene therapies aimed at fighting cancers. All conditions are met to implement and monitor all types of projects - target discovery and validation, cellular engineering, proof of concept, pre-clinical research… right up to the product being completely ready for manufacturing.