2 Years of Maintenance May Be Enough for Some Patients With Standard-Risk Multiple Myeloma: ENDURANCE Trial Breakdown

A recent major new study published in The New England Journal of Medicine is helping doctors and patients rethink how long maintenance therapy needs to continue after initial treatment for some patients with multiple myeloma. The findings from the phase 3 ENDURANCE trial offer reassuring news for many people with standard-risk disease who are not planning an early stem cell transplant.

What Is Maintenance Therapy in Multiple Myeloma?

After the first phase of treatment, called induction therapy, many patients with multiple myeloma receive ongoing maintenance therapy. This is usually the oral medicine lenalidomide. The goal is to keep the myeloma under control longer than they would if they received no maintenance therapy.

For years, the common approach has been to continue lenalidomide indefinitely, until the disease progresses or side effects become intolerable to the patient and they need to stop the medication. However, the optimal duration of maintenance therapy has remained an open question. In the ENDURANCE trial, a team of researchers led by Shaji Kumar, MD, of Mayo Clinic, evaluated whether a shorter, fixed period of treatment could work just as well while causing fewer long-term side effects.

What Did the ENDURANCE Trial Study?

The ENDURANCE trial focused on adults with newly diagnosed, standard-risk multiple myeloma who were not receiving an upfront autologous stem cell transplant. Multiple myeloma has different risk categories, which are based mainly on genetic changes found in the myeloma cells through bone marrow testing, along with certain blood test results. They are a guide, not a prediction of exactly what will happen for any one person.

The study looked at individuals who were in the standard-risk category. After completing initial induction therapy with a proteasome inhibitor plus lenalidomide and dexamethasone, 516 patients were randomly assigned to one of two groups:

• Indefinite (continuous) lenalidomide—continue the medicine until the myeloma progresses or side effects require stopping.
• Fixed-duration lenalidomide—take the medicine for 2 years and then stop (unless the disease progresses earlier).

The main question the researchers asked was whether continuous treatment would help people live longer than stopping after 2 years. The study’s primary end point was OS and patients were followed for a median of about 7 years (86 months).

Key Results: Similar Survival, Fewer Side Effects with the Shorter Course

At 7 years:

• OS was similar between the two groups: 68.6% in the continuous group and 69% in the 2-year group. There was no meaningful difference.
• Progression-free survival (the time until the myeloma worsened or a person died) was slightly higher with continuous therapy (36.1% vs 29.7%), but this difference was not statistically significant.

Importantly, continuous treatment came with more drawbacks:

• Higher rates of significant (grade 3 or higher) non-blood-related side effects (48.2% vs 31.5%).
• More fatigue, anemia, and diarrhea.
• A somewhat higher rate of second primary cancers over 5 years.

Why This Matters for Patients

These results suggest that, for many people with standard-risk multiple myeloma who do not undergo early transplant, taking lenalidomide for about 2 years can provide the same long-term survival benefit as staying on it indefinitely. Additionally, these individuals can reduce the burden of ongoing side effects and potentially the risk of developing other cancers.

Stopping after a fixed period also leaves the option open to restart lenalidomide or try other effective treatments later if needed. Quality of life is a major consideration during long-term treatment, and this study supports a more personalized approach that balances disease control and maintaining a good quality of life with fewer side effects.

An important caveat is that these findings apply specifically to standard-risk patients who did not receive upfront transplant after a proteasome inhibitor–lenalidomide induction. Results may differ based on risk of disease (high-risk disease), whether patients receive a transplant, or whether they are treated with different modern combinations (including anti-CD38 antibodies). Decisions about maintenance duration should always be made with a patient’s oncology team.

Looking Ahead

The ENDURANCE trial provides the first large, randomized evidence that a fixed 2-year course of lenalidomide maintenance can be a reasonable standard for many standard-risk patients in this setting. It challenges the idea that “continuing longer on therapy is always better” and opens the door to discussions that prioritize both length and quality of life.

If you or a loved one is currently on or considering maintenance therapy, talk with your care team about these results and how they might apply to your situation. Ongoing research continues to refine the best approaches for every patient.

This summary is for educational purposes and is based on the published ENDURANCE trial results. It is not a substitute for personalized medical advice. Always consult your healthcare providers for guidance specific to your care.