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This is an excerpt of a Reuters article. Read the full story here.

Ruben Niesvizky, M.D.

Early treatment with lenalidomide plus dexamethasone delays time to progression in some high-risk patients with smoldering multiple myeloma (MM), researchers in Spain report.

"The standard of care for most patients with smoldering multiple myeloma is observation until the development of myeloma-defining events," write Dr. Maria-Victoria Mateos of the University Hospital of Salamanca and colleagues in The Lancet Oncology, online July 9.

"However, this no-treatment approach, which was probably suitable in the era of restricted treatment options also associated with notable toxic effects, might not be the best option in a new era of myeloma treatment," they add.

The current study is a six-year follow-up of the multicenter QuiRedex study, designed in 2006 to compare early treatment with lenalidomide - a thalidomide derivative manufactured by Celgene - plus dexamethasone with observation in patients with high-risk smoldering MM.

A total of 57 patients received early treatment with lenalidomide plus dexamethasone; 62 were not treated (observation). 

For up to two years, patients in the treatment group received nine four-week induction cycles: 25 mg lenalidomide daily on days 1-21, plus 20 mg dexamethasone on days 1-4 and days 12-15, followed by maintenance therapy of 10 mg lenalidomide daily on days 1-21 of each 28-day cycle.

Among the findings, the team determined that 39% of patients in the treatment group progressed to MM compared to 86% of patients in the observation group. The time to progression was significantly lower in the treatment group (hazard ratio, 0.24; p<0.0001).

At data cutoff, 18% of patients had died in the treatment group compared with 36% in the observation group (HR, 0.43; p=0.024). There was no significant difference in survival among patients who had received subsequent treatments at the time of progression to active disease (HR, 1.34; p=0.50).

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Dr. Mateos told Reuters Health by email, "The most important finding of this (study) is that early treatment with lenalidomide and dexamethasone in asymptomatic myeloma patients at high risk of progression has demonstrated to prolong overall survival."

"This time to-event data was a secondary point of the study and (was significant) in 2013 when the trial was first published. The median follow-up at that time was 40 months. Now, the median follow-up is 75 months and this benefit has been confirmed," she said.

Dr. Mateos added, "Moreover, with this long-term follow-up, the benefit in terms of time to progression is also sustained. The survival from progression to active disease is not different in both arms indicating that the early treatment in asymptomatic patients did not induce more resistant relapses."

Although no drug has been approved for asymptomatic myeloma, "we consider that the updated results of this trial support the early treatment for high-risk smoldering myeloma patients," she concluded.

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Dr., director of the Multiple Myeloma Center at New York-Presbyterian and Weill Cornell Medicine, told Reuters Health by email, "These are provocative and potentially paradigm-changing observations; however, before considering this, one should recognize that further experience and new intervention trials in this population are warranted."

Dr. Niesvizky noted that "modern day myeloma diagnostics utilize advanced imaging such as MRI and PETCT, (and) the International Myeloma Working Group recently changed the definition of myeloma by adding abnormal MRI findings."

"The fact that none of these more sensitive techniques were used routinely in the QuiRedex trial raises the question of whether serially using these techniques would have identified more people at risk or would have allowed earlier interventions," he said. And because radiology was used only at screening and upon demand, "we ignore the real effect of treatment on bona fide skeletal progressive disease."