Precancerous Myeloma Progression Reduced by Lenalidomide

Smoldering multiple myeloma (SMM), a precancerous condition, may be significantly reduced from progressing to cancer by treatment with lenalidomide (Revlimid) in patients at moderate or high risk, according to a phase 2/3 E3A06 randomized clinical trial.

The study was presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in an oral abstract session.

SMM, which is a precursor to symptomatic myeloma, is also known as asymptomatic myeloma. Typically, patients with symptomatic myeloma have evidence of organ damage, such as bone lesions or fractures. Other symptomatic issues can include kidney problems, anemia or other bone marrow issues, or high blood calcium. In many cases, patients who have developed symptomatic myeloma have irreversible morbidity and oftentimes mortality associated with their disease.

In an ASCO presscast, study author Sagar Lional, MD, FACP, chief medical officer at Winship Cancer Institute of Emory University, gave an overview of the study results.

“One of the challenges that we’ve struggled with in myeloma is trying to identify which patients are at highest risk of progression and trying to intervene in those patients versus patients that are at lower risk and leaving them alone because their median time to develop myeloma may be much longer,” Dr Lional said during the presscast.

The trial enrolled patients with intermediate or high-risk SMM in 2 phases. In phase 2, 44 patients received lenalidomide to allow investigators to assess its potential efficacy. In phase 3, investigators randomly assigned 182 patients to a 25-mg pill of lenalidomide daily for 21 of the first 28 days of a therapy cycle, or observation, according to the study.

The researchers then stratified the patient groups based on whether they were diagnosed with high-risk SMM within that past year or more than a year after enrollment and used MRIs of the spine and pelvis to detect disease at enrollment.

In both the phase 2 and phase 3 trials, lenalidomide led to improved outcomes for patents with moderate- and high-risk SMM in the following ways:

• Progression-free survival (PFS): In phase 2, after 3 years on the trial, 87% of the enrollees were alive without SMM progressing to multiple myeloma (PFS defined as the time before myeloma develops). In phase 3, after 1, 2, and 3 years on the trial, respective PFS rates were 98%, 93%, and 91% respectively, for those who received lenalidomide and 89%, 76%, and 66%, respectively, for those who did not receive the treatment and were just observed.
• Toxicity: The proportion of people who could not tolerate lenalidomide was concerning, with 80% of people in phase 2 and 51% of people in phase 3 discontinuing the medicine due to toxicity.

According to Dr Lional, the study showed that early intervention with a prevention strategy, not a treatment strategy, can reduce the risk of conversion to symptomatic myeloma.

Common adverse effects, including fatigue and non-blood or bone-related adverse effects were seen in approximately 28% of patients. A low count of neutrophils, also known as high-grade neutropenia, was seen in approximately 5% of patients. Individuals administered lenalidomide did not experience a difference compared with those who did not take the therapy, according to the results.

The investigators are currently performing an analysis of patients who stopped taking lenalidomide due to toxicity to determine whether limited doses of the medicine may have delayed progression to multiple myeloma.

Reference

Lonial S, Jacobus SJ, Weiss M, et al. E3A06: Randomized phase III trial of lenalidomide versus observation alone in patients with asymptomatic high-risk smoldering multiple myeloma. J Clin Oncol 37, 2019 (suppl; abstr 8001). Presented at: 2019 ASCO Annual Meeting. May 31-June 4, 2019.