Lenalidomide Maintenance vs Observation For Newly Diagnosed Myeloma

Patients with newly diagnosed multiple myeloma treated with maintenance lenalidomide had significantly better progression-free survival compared with observation, according to the results of the Myeloma XI trial published in Lancet Oncology.

With a median follow-up of about 2.5 years, patients assigned to maintenance lenalidomide had a 19-month improvement in median progression-free survival (PFS) compared with observation.

“The results of the Myeloma XI trial contribute to a body of evidence that suggests that the use of lenalidomide as maintenance therapy should be considered for patients with newly diagnosed multiple myeloma, of all cytogenetic risk groups, after autologous stem-cell transplantation,” wrote Graham H. Jackson, MD, of the Northern Institute for Cancer Research, United Kingdom, and colleagues.

The study randomly assigned 1,917 patients 2:1 to either maintenance lenalidomide or observation. All patients had completed assigned induction therapy and achieved at least a minimal response to protocol treatment. The trial had co-primary endpoints of progression-free and overall survival.

With a median follow-up of 31 months, patients assigned to maintenance lenalidomide had a median PFS of 39 months compared with 20 months for observation (hazard ratio [HR], 0.46; 95% CI, 0.41–0.53; P < .0001). Improvements in PFS were found in all prespecified subgroups.

In transplant-eligible patients, the median PFS was 57 months with lenalidomide compared with 30 months for observation (HR, 0.48; 95% CI, 0.40–0.58; P < .0001). In ineligible patients the median PFS was 26 months with lenalidomide compared with 11 months for observation (HR, 0.44; 95% CI, 0.37–0.53; P < .0001).

“This finding suggests that lenalidomide maintenance might not negatively affect the activity of subsequent treatment by selecting for more aggressive or drug-resistant myeloma clones,” the researchers wrote. “This hypothesis is also supported by previous analyses indicating that lenalidomide maintenance did not increase genomic change or mutational load.”

There was no significant difference in overall survival between the study arms (3-year overall survival 78.6% vs 75.8%).

When the researchers looked at outcomes by transplantation status, the 3-year overall survival in transplant-eligible patients was 87.5% for lenalidomide compared with 80.2% for observation (HR, 0.69; 95% CI, 0.52–0.93; P = .014). The difference in overall survival was not statistically significant though in transplant-ineligible patients (66.8% vs 69.8%; P = .88).

Additional subgroups analyses of overall survival showed differences for standard-risk patients (86.4% in lenalidomide vs 81.3% for observation), and high-risk patients (74.9% vs 63.7%). However, the researchers noted that the study was not powered to observe these differences in subgroups.

Maria-Victoria Mateos, MD, PhD, and Veronica Gonzalez de la Calle, MD, PhD, of the University Hospital of Salamanca, Spain, wrote that maintenance lenalidomide is an option for every patient with newly diagnosed multiple myeloma, but that more research is needed into new therapies or combination to improve overall survival in these patients.

“The results of this study support the benefit of lenalidomide maintenance across different subgroups of patients and highlights the progression-free survival benefit in patients with high-risk cytogenetic abnormalities,” they wrote. “However, it is important to note that lenalidomide did not overcome the poor prognosis that the presence of high-risk abnormalities confer to patients, and therefore novel treatments to improve the outcomes of these patients are needed.”