Does Multiple Myeloma Maintenance Therapy Need to Continue Indefinitely?

For patients with multiple myeloma, maintenance therapy has become an established strategy for extending disease control following initial treatment. However, findings from the phase 3 ENDURANCE trial (NCT01863550) challenge whether continuing lenalidomide (Revlimid; Bristol Myers Squibb) until disease progression provides additional survival benefits for all patients.¹

Published in The New England Journal of Medicine, the study found no statistically significant difference in overall survival (OS) between indefinite lenalidomide maintenance and a fixed 2-year treatment duration among patients with standard-risk newly diagnosed multiple myeloma who did not undergo upfront autologous stem-cell transplantation (ASCT). Patients receiving prolonged therapy experienced more adverse events, raising questions about how maintenance duration should be determined in clinical practice.¹

Seven-Year Survival Outcomes Challenge Continuous Treatment

The randomized phase 3 ENDURANCE trial evaluated 516 patients who completed induction treatment with a proteasome inhibitor and lenalidomide-containing regimen. Participants were assigned to receive either indefinite lenalidomide maintenance until disease progression (n = 260) or fixed-duration maintenance for 2 years (n = 256).¹

At a median follow-up of 86 months, 7-year OS was 68.6% in the indefinite-duration group compared with 69.0% in the fixed-duration group, representing a difference of −0.4 percentage points (95% CI, −9.0 to 8.3; P = .93). Eighty deaths occurred in each treatment group.¹

Progression-free survival (PFS) numerically favored indefinite treatment, with 7-year rates of 36.1% versus 29.7% for fixed-duration maintenance. However, the difference did not translate into a statistically significant OS benefit.¹

The findings suggest that prolonged disease control does not necessarily translate into longer survival for every patient. The absence of a significant survival difference does not establish that the 2 strategies are equivalent, and the results should be interpreted within the study's standard-risk, non–upfront-transplant population.

Longer Treatment Comes With Greater Toxicity

Although survival outcomes were similar, treatment duration influenced the incidence of adverse events.

Grade 3 or higher nonhematologic adverse events occurred in 48.2% of patients receiving indefinite maintenance compared with 31.5% receiving fixed-duration therapy. The 5-year cumulative incidence of second primary cancers, excluding nonmelanoma skin cancers, was also numerically higher with indefinite treatment (11.2% vs 8.3%).¹

These differences are relevant for patients who may remain on lenalidomide for years after achieving disease control. Fatigue and gastrointestinal adverse effects can interfere with daily functioning, while treatment-related complications may require dose modifications or interruptions.²

The findings also introduce a broader consideration: whether extending treatment exposure is justified when additional survival benefit has not been demonstrated in the population studied.

An accompanying New England Journal of Medicine editorial questioned the assumption that longer maintenance necessarily produces better outcomes, emphasizing the need to reconsider treatment duration as myeloma management evolves.³

What Oncology Pharmacists Should Consider

For oncology pharmacists, the ENDURANCE findings reinforce the importance of assessing maintenance therapy as an ongoing treatment decision rather than an indefinite commitment made at initiation.

Lenalidomide requires continued monitoring for hematologic toxicity, including neutropenia and thrombocytopenia. Its prescribing information also warns of thromboembolic complications and second primary malignancies. Pharmacists play a central role in recognizing adverse effects, evaluating dose adjustments, and supporting adherence throughout treatment.²

These responsibilities become particularly important when patients remain clinically stable but experience cumulative treatment burden.

Current American Society of Clinical Oncology guidance continues to support lenalidomide maintenance following ASCT, while emphasizing individualized decisions regarding treatment duration. The ENDURANCE findings should therefore not be extrapolated to transplant recipients or patients with high-risk disease, whose treatment needs may differ substantially.⁴

Pharmacists can contribute to shared decision-making by reviewing tolerability and discussing the implications of continued therapy with the oncology team. For eligible patients considering fixed-duration treatment, counseling should also address the importance of ongoing disease surveillance after maintenance ends.

Reconsidering the Duration of Myeloma Care

The ENDURANCE trial provides randomized evidence questioning the need for indefinite lenalidomide maintenance in a defined population with standard-risk multiple myeloma.

Although additional research is needed to determine which patients benefit most from prolonged treatment, the findings support a more individualized approach to maintenance decisions.

For oncology pharmacists, the clinical priority remains balancing sustained disease control against the consequences of continued medication exposure. As treatment options expand and patients live longer with multiple myeloma, identifying when maintenance therapy remains beneficial may become as important as determining when to initiate it.

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. doi:10.1056/NEJMoa2600157

2. Revlimid (lenalidomide) capsules, for oral use. Prescribing information. Bristol Myers Squibb; DailyMed. Updated March 23, 2024. Accessed October 22, 2026. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=5fa97bf5-28a2-48f1-8955-f56012d296be

3. Mian H, Costa LJ. Time to stop? Rethinking the duration of maintenance treatment in multiple myeloma. N Engl J Med. 2026;395(3):302-303. doi:10.1056/NEJMe2604761

4. Banerjee R, Messersmith H, Ebraheem M, et al. Treatment of multiple myeloma: ASCO Living Guideline, Version 2026.1.3. J Clin Oncol. Published online September 30, 2026. doi:10.1200/JCO-26-02399