Early treatment of asymptomatic myeloma, which has a high risk of developing into active multiple myeloma, can significantly improve the course of the disease, delay progression and increase patient survival. These were the conclusions of a clinical trial carried out by the Spanish Myeloma Group (GEM-PETHEMA), which unites specialists from more than 80 Spanish hospitals, published in the August issue of The New England Journal of Medicine.

The results of the study show the need to identify patients with asymptomatic myeloma at high risk of developing the active form, and the advantages of considering this as an early symptomatic myeloma. Moreover, the possibility that early treatment in this phase can improve the subsequent course of multiple myeloma constitutes a change in paradigm in the routine clinical management of patients with this type of asymptomatic cancer, who until now did not receive any treatment if they did not present symptoms.

A total of 21 Spanish hospitals belonging to GEM-PETHEMA and three Portuguese centers have participated in this global study, coordinated by doctors Jesus San Miguel and Maria Victoria Mateos, from the haematology department of the Salamanca University Hospital.

Multiple myeloma is a type of cancer produced by the malignant transformation of plasma cells present in the bone marrow which then produce, instead of normal immunoglobulins, a special type of immunoglobulin called the monoclonal component. The symptoms arise from bone lesions and correspond to pain, anaemia, hypercalcemia and renal insufficiency. Patients with this kind of neoplasm also tend to be at greater risk of infections.

Miguel said, "New medicines have appeared over the past few years for the treatment of multiple myeloma, which has led to significant improvements in life expectancy, which are now on average from five to seven years."

Before the appearance of symptoms of the disease, there is a period during which the myeloma is inactive or asymptomatic (smoldering), and this clinical trial has focused specifically on this stage. "Although there is a proliferation of plasma cells in the bone marrow that produce the monoclonal immunoglobulin, as these patients were asymptomatic they did not receive any treatment. In fact, the clinical trials that assessed the effectiveness of early treatment before the appearance of symptoms, compared to delayed treatment when the patient is already symptomatic, found no differences in survival," said Miguel.

However, Mateos said, "There is a reasonable risk, 10% annual risk, that these patients later become symptomatic, meaning half of the patients over a five year period in fact do so. An important point to consider is that the risk is not uniform over time, meaning there are different kinds of patients with asymptomatic myeloma."

The Spanish Myeloma Group already has identified three groups of patients among those affected by asymptomatic myelomas, "one with a very low risk of developing active myeloma, another group of intermediate risk and a third, high-risk group, in which more than half develop multiple myeloma in less than two years,” said Mateos. “Our study has focused on the latter group which we call latent high-risk myeloma."

A total of 120 individuals participated in the randomized trial and were divided into two groups. Half did not receive any therapy until the appearance of myeloma symptomatology, the standard treatment approach to date. The other 60 were given anti-myeloma treatment in order to establish whether early administration of the treatment could delay the onset of symptoms.

"The treatment chosen was lenalidomide, a new immunomodulator therapy proven highly effective in patients with active myeloma, in combination with dexamethasone, a corticosteroid. This therapy has the additional advantage of being of oral administration and presents an excellent tolerance level," said Miguel.

Results of the trial show a high percentage response to treatment in the experimental group, above 80%. "The primary study objective was also being met: the risk of disease progression to symptomatic myeloma was significantly lower (5.59 times lower) in patients treated early on compared to non-treated patients. Around 74% of non-treated patients have already progressed to active myeloma while only 22% of patients treated early with lenalidomide and dexamethasone developed the active disease," said Miguel. Also, "94% of patients receiving treatment were still alive at five years compared to 78% in the non-treated group. The therapy was well-tolerated by most patients."

With these findings, GEM-PETHEMA is a world pioneer in myeloma research in its line of work to improve the treatment and the future of patients suffering this malignant neoplasm.