Early treatment with lenalidomide may delay progression to symptomatic multiple myeloma (MM) in patients with smoldering MM, according to a new study published in The Journal of Clinical Oncology.

Smoldering MM is an asymptomatic precursor stage of the disease, with a risk of progression to the symptomatic stage of 10% per year. Typically, observation is the standard of care for patients with smoldering MM until the onset of progression is seen. Patients who progress to symptomatic disease will experience bone and other myeloma-related organ damage.

In a previous study conducted in 2015, early intervention with lenalidomide plus dexamethasone was shown to improve progression-free survival (PFS) and overall survival (OS) compared with observation; however, the study was not able to determine the isolated value of lenalidomide.

For the current study, the authors aimed to determine whether the immunomodulatory effects of lenalidomide alone could prevent end-organ dysfunction without the need for corticosteroids.

The study included 182 patients, 92 of whom received lenalidomide. The other 90 patients did not receive lenalidomide but underwent standard of care observation. Lenalidomide was administered orally at a dose of 25 mg on days 1 to 21 of a 28-day cycle.

According to the findings, median OS follow-up was 82 months (95% CI, 72 months to 84 months) and the 5-year PFS was 78% (95% CI, 65% to 93%). Six deaths occurred: 2 in the lenalidomide arm versus 4 in the observational arm (hazard ratio for death, 0.46; 95% CI, 0.08 to 2.53).

At the second planner interim analysis, PFS was significantly longer for lenalidomide compared with observation. One-, 2-, and 3-year PFS was 98%, 93%, and 91% for the lenalidomide arm versus 89%, 76%, and 66%, respectively.

Approximately half of all patients receiving lenalidomide responded to therapy, with no change reported among patients who were observed without treatment, according to the study.

“Our findings are in line with a smaller trial in 2015 by researchers in Spain,” senior author Vincent Rajkumar, MD, a Mayo Clinic hematologist, said in a press release. “In conjunction with the Spanish data, our findings support early therapy for patients with high-risk smoldering multiple myeloma.”

Regarding safety, serious adverse events occurred in 28% of patients taking lenalidomide, but these events were considered manageable with dose reduction, according to Rajkumar.

The authors noted that the benefit of lenalidomide was observed in most subgroups, although many subsets are relatively small; however, they indicated that it is too early to determine the impact on OS in the study.

“Prevention of serious symptomatic end-organ damage–osteolytic bone lesions, acute renal failure, etc, is by itself an important goal given the longevity of patients with myeloma with modern therapy and should be recognized as an important goal of therapy in the smoldering population,” the authors wrote.

References

Lonial S, Jacobus S, Fonseca R, et al. Randomized trial of lenalidomide versus observation in smoldering multiple myeloma. Journal of Clinical Oncology. 2019. Doi: 10.1200/JCO.19.01740

Lenalidomide may delay onset of myeloma-related bone, organ damage [news release]. Mayo Clinic’s website. https://newsnetwork.mayoclinic.org/discussion/lenalidomide-may-delay-onset-of-myeloma-related-bone-organ-damage/. Accessed October 28, 2019.