A Spanish study published in the prestigious The New England Journal of Medicine constitutes a milestone in myeloma treatment

- The study carried out by the Spanish Myeloma Group (Grupo Espanol de Mieloma, GEM-PETHEMA), shows that early treatment of patients with asymptomatic myeloma delays disease progression and prolongs survival.

- This research provides the foundations for future studies and changes the direction of the current concept of treatment and the fight against this type of haematologic cancer.

MADRID, Aug. 1, 2013 /PRNewswire/ -- 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), 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 the Spanish Myeloma Group (GEM-PETHEMA) and 3 Portuguese centres have participated in this globally pioneering study, coordinated by doctors Jesus San Miguel and Maria Victoria Mateos, from the Haematology Department of the Salamanca University Hospital.

A 10% annual risk of developing into multiple myeloma

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.

As Dr. San Miguel explained, "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 5 - 7 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 had 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."

However, according to Dr. Mateos, "There is a reasonable risk, 10% annual risk, that these patients later become symptomatic, meaning that 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 that there are different kinds of patients with asymptomatic myeloma."

She explains how the Spanish Myeloma Group has already 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. Our study has focused on the latter group which we call latent high-risk myeloma."

Oral administration and good tolerance to treatment

A total of 120 individuals participated in the randomised trial and were divided into two groups: half of them did not receive any therapy until the appearance of myeloma symptomatology, the standard treatment approach to date. The other 60, however, the experimental group, 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 that had 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," explained doctor San Miguel.

He went on to describe how the results of the trial, show a high percentage response to treatment in the experimental group, above 80%.[i] "At the same time, 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."

However, even more important than this, according to the trial investigators, is that the therapy increased survival in patients treated early with lenalidomide and dexamethasone. "94% of patients receiving treatment were still alive at five years compared to 78% in the non-treated group. Moreover, the therapy was well-tolerated by most patients."

GEM-PETHEMA, the global pioneering research group

With these findings, the Spanish Myeloma Group (GEM-PETHEMA), which unites specialists from more than 80 Spanish hospitals, 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.

According to Dr. Joan Blade, of the Barcelona Hospital Clinic and active member of this research group "we first started researching multiple myeloma in Spain in 1985, although the Spanish Myeloma Group (GEM/PETHEMA) wasn't set up until the year 2000. It unites the main sources of knowledge of this haematologic disease in the country, and is a global centre of excellence in this area. This study is a milestone in the history of Spanish research, as shown by its publication in the prestigious New England Journal of Medicine."

If we consider this disease in the context of the economic recession and the decline in investment in R&D, Dr. Juan Jose Lahuerta, of the Hospital 12 de Octubre and member of the GEM-PETHEMA Group explained that "during these times, the research that is financed must be carefully selected, and it is important to choose excellence. In 2007, when the trial started, this was not a problem, but the fact that GEM-PETHEMA has always produced high quality work means that the industry can place its trust in our research. This is shown clearly by these results, which mark for us the path research must follow to achieve a cure for patients with multiple myeloma in the near future."

It is important to recall that the GEM-PETHEMA Group has helped establish the standards for first-line treatment in patients under and over 65 years-old, and also to establish worldwide the importance of high quality and precise measurements of therapeutic responses in myeloma, using the approach known as "minimal residual disease."

References
[i] NEJM 2013; 369:438-447