Rethinking Myeloma Lenalidomide Maintenance

For years, the standard of care for newly diagnosed multiple myeloma (NDMM) has leaned toward continuous lenalidomide maintenance therapy until disease progression. However, results from the phase 3 ENDURANCE trial (NCT01863550) are challenging this paradigm, providing the first randomized evidence that a fixed two-year duration of maintenance may be sufficient for certain patients without sacrificing overall survival (OS).

Trial Design and Survival Outcomes

The study, co-authored by Sagar Lonial, MD, FACP, FASCO, Chief Medical Officer at Winship Cancer Institute of Emory University, focused on patients with standard-risk NDMM who did not undergo up-front autologous stem-cell transplantation.

Following induction with a proteasome inhibitor–lenalidomide combination, 516 patients were randomized to either indefinite (continuous) lenalidomide or a fixed two-year course.At a median follow-up of 86 months, researchers found that OS rates did not significantly differ between the two arms.

The seven-year OS was 68.6% in the indefinite group versus 69.0% in the fixed-duration group. Furthermore, while progression-free survival (PFS) was higher in the indefinite group (36.1% vs. 29.7%), the difference was not statistically significant.

Implications for Oncology Nursing

For oncology nursing teams, striking data points involve toxicity and patient safety. Indefinite therapy was associated with a significantly higher burden of adverse events (AEs). Grade 3 or higher nonhematologic AEs occurred in 48.2% of the indefinite-duration group compared to 31.5% in the fixed-duration group. Additionally, the five-year cumulative incidence of second primary cancers (excluding nonmelanoma skin cancer) was higher in those receiving continuous therapy (11.2% vs. 8.3%).

Nurses play a critical role in monitoring these long-term toxicities and managing the cumulative side effects that often lead to decreased quality of life. The findings suggest that stopping therapy at two years could alleviate this burden for many patients without compromising their long-term survival.

Clinical Nuance and Joint Decision-Making

Despite these results, Lonial emphasized in an interview that this trial is not a license for every patient to stop maintenance at the two-year mark. He noted that the applicability of this data depends heavily on individual clinical situations.

He advised that clinicians and nurses should consider the depth of response, the specific induction regimen used, and the side effects an individual has experienced. He also pointed out that many patients in 2026 are receiving quadruplet induction therapies rather than the triplet (RVD) used in the trial, which may further influence the decision to discontinue.

Ultimately, Lonial described this data as a framework for joint decision-making between the clinical team and the patient, allowing for a more personalized approach to maintenance duration.

References

1. Kumar S, Jacobus S, Cohen A, et al. Continuous or Fixed-Duration Maintenance Therapy in Multiple Myeloma. N Engl J Med. 2026;395(3):221-232.
2. Winship Cancer Institute of Emory University. Multiple myeloma trial provides first randomized evidence for optimal duration of maintenance therapy. Published July 17, 2026. Accessed August 4, 2026.