Al-Ola Abdallah, Associate Professor and Plasma Cell Disorder Program Director of the Division of HMCT at the University of Kansas Medical Center, shared on X:
“Read and don’t Judge this.
NEJM Practice-Changer?
Can We Finally Stop Lenalidomide Maintenance at 2 Years in Standard-Risk Myeloma?
A deep dive into the ENDURANCE maintenance trial published in the New England Journal of Medicine.
Background
For years, lenalidomide maintenance has been continued until progression, largely because previous trials compared maintenance vs no maintenance—not continuous vs fixed duration. This phase III trial finally addressed a question we’ve all been asking:
Is indefinite maintenance really necessary?
Study Design
Phase III ENDURANCE trial
516 patients with standard-risk, transplant-deferred/ineligible newly diagnosed MM
After KRd or VRd induction:
Continuous lenalidomide until progression or fixed-duration lenalidomide for 2 years
Primary endpoint: Overall Survival (OS)
The Headline Result No Overall Survival benefit 7-year OS:
- Continuous: 68.6%
- Fixed 2 years: 69.0%
- P = 0.93
After nearly 7 years of follow-up, longer maintenance did not improve survival.
Progression-Free Survival
There was only a numerical, not statistically convincing, improvement.
Median PFS
- 42.5 months
- vs 38.9 months
7-year PFS
- 36.1%
- vs 29.7%
Absolute difference: 6.4%
No clear clinically meaningful separation.
Toxicity Matters
Continuous therapy came at a cost.
Grade ≥3 adverse events:
- 62.4% vs 46.9%
Grade ≥3 non-hematologic toxicity:
- 48.2% vs 31.5%
More discontinuations due to:
- Fatigue
- Cytopenias
- Diarrhea
- Neutropenia
Higher cumulative incidence of second primary cancers: 11.2% vs 8.3%.
Why is this Important?
Longer treatment means:
- Higher cost
- More clinic visits
- More chronic toxicity
- Lower treatment-free time I
f survival is unchanged, we should carefully ask:
Are patients benefiting enough to justify indefinite therapy?
Critiques
Every landmark study deserves careful interpretation.
- Only standard-risk patients were included.
- No upfront ASCT population.
- Modern MRD-guided discontinuation was not incorporated.
- High-risk disease remains unanswered.
- Only 516 of 1087 enrolled patients reached the maintenance randomization.
- The trial observed 160 deaths, fewer than the planned 364, reducing statistical power for OS.
Clinical Perspective
This trial should be interpreted as:
- Maintenance remains beneficial.
- Extending therapy beyond 2 years may not improve overall survival for standard-risk patients treated without upfront transplant.
Duration – not simply maintenance itself – is the question.
Take-Home Messages
- First randomized trial directly comparing continuous vs 2-year lenalidomide maintenance.
- No improvement in overall survival with indefinite therapy.
- Only modest numerical PFS difference.
- Continuous treatment caused substantially more toxicity.
- Results apply only to standard-risk, non-transplant patients.
- Supports future strategies using individualized, MRD-guided maintenance duration rather than routine indefinite therapy. “
Title: Continuous or Fixed-Duration Maintenance Therapy in Multiple Myeloma
Authors: Shaji Kumar, Susanna Jacobus, Adam Cohen, Matthias Weiss, Natalie Callander, Avina Singh, Terri Parker, Michael Green, Raymond Thertulien, Benjamin Parsons, Pankaj Kumar, Prashant Kapoor, Aaron Rosenberg, Elie Dib, Daniel Almquist, Jeffrey Zonder, Edward Faber, Zihan Wei, Kenneth Anderson, Sagar Lonial, Paul Richardson, Robert Orlowski, Lynne Wagner, S. Vincent Rajkumar
Read also “Myeloma Paper of the Day, July 20th, Suggested by Robert Orlowski” on OncoDaily.
