SEQC Spanish Society of Laboratory Medicine

Dr. Adrián Fontán, President of the SEQC-ML Protein Commission

• Monoclonal gammopathies are a group of diseases characterized by a clonal proliferation of plasma cells that can cause problems such as bone pain, predisposition to infections, as well as kidney, heart or neurological disorders.

• The Clinical Laboratory specialist plays a key role in correctly classifying these patients and providing personalized follow-up and treatment.

• In recent years, new risk stratification systems and treatments have permitted closer monitoring of patients and a delay of progression to symptomatic multiple myeloma, which lacks curative treatment.

The Clinical Laboratory specialist plays a crucial role in the management and monitoring of monoclonal gammopathies, a group of diseases characterized by the clonal proliferation of plasma cells.These can initially manifest asymptomatically and progress to causing problems such as bone pain, predisposition to infections, and kidney, heart or neurological disorders. Laboratory Medicine allows these patients to be correctly classified and to assess the risk of the disease progressing from a premalignant to a malignant condition so as to provide follow-up and treatment tailored to each patient.

On October 2, the Spanish Society of Laboratory Medicine (SEQC^ML) held the course, “Management and Monitoring of Asymptomatic Monoclonal Gammopathy. Evolution of risk stratification models and their clinical importance", within the framework of its virtual training project SEQC^ML ACADEMY, with the aim of addressing the importance of correctly classifying this type of patient, as well as the clinical value of the risk stratification systems.

Monoclonal gammopathies include a wide spectrum of clinical entities that can include asymptomatic conditions, such as monoclonal gammopathy of undetermined significance, which is the most common, or quiescent multiple myeloma. On the other hand, other types of entities present symptoms, caused either by the neoplastic proliferation of plasma cells themselves or by the damage caused by the monoclonal protein they release. The most common are symptomatic multiple myeloma and light chain amyloidosis.

According to the course moderator and President of the SEQC^ML Protein Commission, Dr. Adrián Fontán, when asymptomatic (premalignant) monoclonal gammopathies evolve into symptomatic (malignant) gammopathies, they can cause problems such as bone pain, predisposition to infections, anemia, hyperviscosity, or renal, cardiac or neurological alterations. “Because of this, it is important to be able to assess the risk of progression from asymptomatic to symptomatic disease.”

The cause behind the appearance of this group of diseases is still unknown. Its incidence increases with age, is more common in men than in women, and is also more common in the African-American population than in the Caucasian population. In the words of Dr. Fontán, “the diagnosis of asymptomatic monoclonal gammopathies has increased, since different tools are currently available in the laboratory that, when combined, allow us to achieve greater test sensitivity.”

Currently, in the case of suspected monoclonal gammopathy, a proteinogram and measurement of free light chains together with their serum ratio are performed. Sometimes a urine study is necessary. In the case of a monoclonal gammopathy being diagnosed, a whole panel of tests is deployed that involve different specialties and especially Clinical Laboratory professionals. The diagnosis is made around the sixth and seventh decades of life. The follow-up of monoclonal gammopathies will depend on the patients' risk of progression. “This risk is assessed based on the type of immunoglobulin, its concentration, concentration of free light chains, immunoparesis, bone marrow status, genetic tests of tumor cells, as well as imaging tests,” indicated Dr. Fontán.

Precision medicine, key in the management of monoclonal gammopathies

Risk stratification models allow for the assessment of the risk of progression from premalignant to malignant disease in each patient. As Dr. Fontán pointed out, “it is important to correctly classify patients in order to provide adequate monitoring and treatment. That is, applying precision medicine so that each patient is unique. The Clinical Laboratory has an important role in this area, since for the management of the patient the analytical results are going to be decisive."

In the words of Dr. Fontán, in recent years, having better classification systems and better treatments has resulted in closer monitoring of those patients with a higher risk of progression and also delayed progression towards symptomatic multiple myeloma. According to him, patients diagnosed with monoclonal gammopathy of undetermined significance, as well as those with asymptomatic multiple myeloma at low or intermediate risk of progression to symptomatic multiple myeloma, do not need treatment.

With respect to asymptomatic multiple myeloma with a high risk of progression, it has been shown that applying treatment can delay the progression to symptomatic multiple myeloma. “Therefore, it is better to treat these types of patients rather than maintain a wait-and-see attitude. Finally, it is important to remember that symptomatic multiple myeloma currently has no curative treatment and therefore it is very important to delay progression,” concluded Dr. Fontán.