Diagnosis and management of smouldering myeloma

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Published: 2 May 2018
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Prof Maria-Victoria Mateos - University Hospital of Salamanca, Salamanca, Spain

Prof Mateos speaks with ecancer at the 2018 Myeloma Knowledge Exchange about how to quantify the risk level for a patient with smouldering myeloma.

She outlines the standard of care for patients with high-risk smouldering myeloma.

ecancer's filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

Today I discussed with the audience about smouldering myeloma. Smouldering myeloma is a plasma cell disorder characterised by the presence of an M-component in the serum usually higher than 3g/dL, and a plasma cell bone marrow infiltration between 10% and 60%. But the main feature is that it is an asymptomatic disease so there is not any myeloma related event so patients are completely asymptomatic. In most cases the diagnosis is done at random because in a routine analysis the serum protein monoclonal component is detected.

How do you diagnose a patient as high risk in the smouldering myeloma setting?

First we have to do the diagnosis of smouldering and when we confirm the diagnosis of smouldering what we have to do as the next step is to define the risk of progression to myeloma. Because we know that smouldering is a heterogeneous disease and we can identify patients at low risk of progression to myeloma, 1% per year; patients at intermediate risk of progression to myeloma, 3% per year; and patients at high risk of progression to myeloma, 10% per year. In order to evaluate the risk we can use different risk models. The most common risk model, and I would say the risk model already validated even in clinical trials, is the model proposed by the Mayo Clinic in which we have to consider the size of the monoclonal component and the plasma cell bone marrow infiltration. We know that when a smouldering myeloma patient has more than 3g/dL of monoclonal component and more than 10% of plasma cell bone marrow infiltration the median time to progression to myeloma is approximately two years. However, when these patients have only more than 3g/dL of monoclonal component but the plasma cell bone marrow infiltration is less than 10% the median time to progression is approximately twenty years. So you can understand that it’s very important for the haematologist to identify in which risk group each smouldering myeloma patient is allocated.

What are the treatment options available?

Today, from the general point of view, the standard of care for smouldering myeloma is no treatment. So watch and wait and when the disease becomes symptomatic, so myeloma defining events appear, in this situation patients have to start therapy. However, if we apply the oncologic perspective and, in fact, if we are able to identify patients at higher risk of progression to myeloma, the appropriate question is why not do early treatment to these patients, especially in order to prevent myeloma defining events. Because myeloma defining events means anaemia, renal impairment, hypercalcemia, bone lesions with bone pain, so these myeloma defining events impact on the quality of life of the patients and this is the role of planning an early treatment for high risk smouldering myeloma.

In line with this the Spanish Myeloma Group conducted many years ago a phase III randomised trial showing that the early treatment with lenalidomide and dexamethasone in high risk smouldering myeloma patients was of benefit and, in fact, was able to delay the progression to myeloma with a benefit even also in overall survival. Now at the present time there are more than fifty clinical trials currently ongoing around the world in this specific patient population, high risk smouldering myeloma.

There are two different approaches – the first approach is to try to delay the progression to myeloma. For evaluating this approach there are trials using len/dex plus a monoclonal antibody or just a monoclonal antibody single agent. But together with this conservative approach there is also a more aggressive approach that is currently ongoing, at least in two clinical trials around the world, and the approach is curative. So the Spanish Myeloma Group, together with the International Myeloma Foundation are conducting two trials in which we plan the potential cure for high risk smouldering myeloma patients. In order to evaluate this, what we are planning is induction with carfilzomib, lenalidomide and dexamethasone, transplant, consolidation with carfilzomib, lenalidomide and dexamethasone and maintenance for up to two years. This is basically the Spanish approach and the American approach is similar plus the monoclonal antibody daratumumab. Today we have to wait to know the results of these trials in order to definitely plan an early treatment for all high risk smouldering myeloma.