Early treatment with lenalidomide and dexamethasone in patients with high-risk smoldering myeloma significantly delayed progression to symptomatic disease and prolonged survival with a good safety profile. If further validated, the results of this trial could change the current treatment paradigm for smoldering myeloma patients, according to the researchers, who published the results of their phase III trial in the New England Journal of Medicine.
Smoldering myeloma is an asymptomatic disease with a current standard of care that calls for no treatment until symptoms have developed. However, the diagnosis of smoldering myeloma includes a heterogeneous population ranging from patients with a low-risk for progression to active disease, to patients at high-risk for progression.
“This trial focused, for the first time, on the high-risk group, who has a progression risk to symptomatic myeloma of 50% at 2 years,” said Jess-F. San Miguel, MD, PhD, from the department of hematology at the University of Salamanca, Spain. “In this cohort, we have investigated the role of early treatment through a phase III randomized trial comparing early treatment vs observation.”
From November 2007 to June 2010, researchers at 22 centers in Spain and Portugal randomly assigned 119 patients considered to have high-risk smoldering myeloma to early treatment (n = 57) or observation (n = 62). Patients assigned to treatment received induction therapy with lenalidomide and dexamethasone followed by maintenance therapy with lenalidomide. The median follow-up was 40 months.
“Lenalidomide plus dexamethasone as early treatment in high-risk asymptomatic myeloma patients significantly delayed the time to progression to symptomatic disease as compared with the observation arm,” San-Miguel said.
At follow-up, the median progression-free survival had not yet been reached in patients assigned to treatment and was 21 months in those assigned observation (P < .001). Only 23% of patients assigned to treatment progressed to symptomatic disease compared with 76% of those assigned observation, resulting in a 0.18 hazard ratio for progression when assigned treatment (95% CI, 0.09–0.32).
“In addition, most of the patients treated early responded to the treatment,” San Miguel told Cancer Network. “What was even more relevant was that there was a benefit in terms of overall survival indicating that patients who received early treatment lived more than patients who did not.”
Seventy-nine percent of patients assigned treatment responded to treatment with a partial response or better during the induction phase; 90% had a partial response or better during the maintenance phase.
Finally, 94% of patients assigned treatment were alive at 3 years compared with 80% in the observation group (P = .03).
According to San Miguel, the results of this trial could change the standard of care for smoldering myeloma patients since the interest will be to begin to identify high-risk patients as the target population for treatment.
“Several other groups, using different drugs, are currently investigating their value in this population,” he said. “This study also provides a strong rationale for future trials using more intensive approaches in which the objective will be to try to cure myeloma patients through early intervention similar to what occur in solid tumors.”