December 31, 2019
5 min read

Early lenalidomide delays multiple myeloma progression

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Sagar Lonial

Early treatment with lenalidomide for smoldering multiple myeloma appeared to delay progression to symptomatic multiple myeloma compared with observation alone, according to results of a randomized phase 3 trial published in Journal of Clinical Oncology.

“We decided to conduct this research after a 2013 trial by Mateos and colleagues of lenalidomide plus dexamethasone compared with observation alone for high-risk smoldering multiple myeloma. My colleagues and I wanted to address the same question, but with lenalidomide alone to remove the side effects of dexamethasone,” Sagar Lonial, MD, FACP, chair and professor in the department of hematology and medical oncology at Winship Cancer Institute of Emory University, and a HemOnc Today Editorial Board Member, told Healio. “It was also becoming clearer that not all patients with smoldering multiple myeloma were the same, and that for the highest-risk group, early intervention may make a big difference.”

Results of the phase 2 run-in trial, which included 44 patients treated with lenalidomide (Revlimid, Celgene) to assess safety, showed PFS rates of 98% at 1 year, 87% at 3 years and 78% at 5 years.

For the open-label, multicenter phase 3 trial, Lonial and colleagues enrolled 182 patients (median age, 64 years; range 31-86) with intermediate- or high-risk smoldering multiple myeloma.

Researchers randomly assigned patients to either 25 mg lenalidomide (n = 92) on days 1 to 21 of every 28-day cycle or observation (n = 90). Both therapy and observation continued until disease progression, toxicity or withdrawal for other reasons.

Patients assigned lenalidomide were required to use thrombosis prophylaxis, which could consist of a minimum of 325 mg aspirin daily, and were encouraged to mobilize stem cells after four to six cycles of therapy.

PFS served as the study’s primary endpoint, with disease progression requiring the development of end-organ damage attributable to multiple myeloma and biochemical progression, according to the researchers.

Median follow-up was 35 months.

Fifty percent of patients (95% CI, 39-61) in the lenalidomide group responded to therapy, whereas no responses occurred in the observation group.

Results showed significantly longer PFS in the lenalidomide group compared with the observation group (HR = 0.28; 95% CI, 0.12-0.62). PFS for the lenalidomide group was 98% at 1 year, 93% at 2 years and 91% at 3 years, compared with 89% at 1 year, 76% at 2 years and 66% at 3 years for the observation group.


Thirty-six patients (41%) in the lenalidomide group experienced grade 3 or grade 4 hematologic and nonhematologic adverse events, including 25 patients (28%) with nonhematologic events. Four deaths occurred in the observation group vs. two deaths in the lenalidomide group (HR for death = 0.46; 95% CI, 0.08-2.53). Forty-five patients in the lenalidomide group discontinued treatment, including 18 who stopped because of adverse events from treatment.

Three-year cumulative incidence of invasive secondary primary cancers was 5.2% in the lenalidomide group vs. 3.5% in the observation group.

“For patients who are in the highest risk category of smoldering multiple myeloma — those who meet the Mayo 20/2/20 criteria, which is the group that benefited most with a reduction in risk for progression to multiple myeloma of more than 90% at 3 years — early intervention does offer benefit,” Lonial told Healio. “The next question is, can more treatment offer additional benefit over simply lenalidomide or lenalidomide plus dexamethasone? We do not know the answer, but it is being tested in the current ECOG trial of lenalidomide plus dexamethasone vs. lenalidomide plus dexamethasone and daratumumab [Darzalex, Janssen Oncology].” – by Jennifer Southall


Mateos MV, et al. N Engl J Med. 2013;doi:10.1056/NEJMoa1300439.

For more information:

Sagar Lonial, MD, can be reached at Winship Cancer Institute of Emory University, 1365 Clifton Road, Building C, Room 3000, Atlanta, GA 30322; email:

Disclosures: NCI funded the study. Lonial reports consultant/advisory roles with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis and Takeda; and research funding from Bristol-Myers Squibb, Celgene and Takeda. Please see the study for all other authors’ relevant financial disclosures.

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