Sustained Post-ASCT MRD Negativity May Signal Lenalidomide Cessation in Myeloma

Updated findings from a prospective cohort study of patients with newly diagnosed multiple myeloma (MM), presented at the 2025 European Society for Medical Oncology (ESMO) Congress, suggest that sustained minimal residual disease (MRD) negativity following standard-of-care autologous stem cell transplantation (ASCT) and 3 years of lenalidomide (Revlimid) maintenance may guide safe discontinuation of maintenance.¹

Earlier results from this study reported in Blood in May 2025 examined 52 patients with MM who discontinued lenalidomide maintenance after 3 years of sustained MRD negativity. Of these patients, 23% (n = 12) patients converted to MRD-positive and restarted maintenance, with 7.6% (n = 4) experiencing disease progression.² Treatment-free survival (TFS) rates at 1, 2, and 3 years were reported as 93.9%, 91.6%, and 75.8%, respectively.

This latest data revealed the outcomes of 54 patients with longer-term follow-up (median, 3.4 years; 95% CI, 3.26–3.92). During this period, 28% (n = 15) of patients converted to MRD-positive, with only 7.4% (n = 4) of patients progressing after lenalidomide reinitiation and 1 death unrelated to MM. For those who experienced MRD conversion, the median time to conversion was 30 months (95% CI, 1.77–3.24 years). The remaining 11 patients who converted to MRD-positive have restarted lenalidomide maintenance and are currently in remission.

Additionally, the updated TFS rates at 1, 2, 3, and 4 years were 94.4% (95% CI, 88.4%–100.0%), 88.1% (95% CI, 79.5%–97.5%), 73.2% (95% CI, 61.1%–87.7%), and 59.2% (95% CI, 44.6%–78.6%), respectively. The 3-year TFS rate appeared to be slightly lower than the investigators’ original hypothesis of 75%.

“Sustained MRD negativity for 3 years seemed to be a reliable biomarker to guide decisions for lenalidomide maintenance discontinuation after ASCT,” said Panagiotis Malandrakis, Clinical Therapeutics department at Alexandra Hospital of the National and Kapodistrian University of Athens.¹

While ASCT followed by lenalidomide maintenance is the current standard-of-care for patients with newly diagnosed MM, little is known regarding the optimal duration of maintenance. This study sought to clarify this threshold to guide safe discontinuation for potential long-term remission.

“The conversion of MRD-negative to MRD-positive always preceded myeloma progression, so perhaps MRD can be used in order to trace these patients that are at an imminent time for progression and that need to be at closer surveillance,” posited Malandrakis in his conclusion. “Longer follow-up will assess the risk of progression in patients who converted from [MRD]-negative to -positive, and if the reinitiation of maintenance had a potential role [in] these patients in stall[ing] their progression as they receive a second line of therapy.”

How was the study designed?

The study was designed as a prospective cohort study of adult patients with MM who were previously treated with 4 to 6 cycles of triplet or quadruplet induction therapy, high dose melphalan, underwent ASCT, and were on lenalidomide maintenance for at least 3 years. The median age of patients at diagnosis was 56 years (range, 36–66).

The objective of the study was to evaluate MRD-related and survival outcomes in patients who discontinue lenalidomide maintenance post-ASCT after 3 years of sustained marrow and imaging MRD negativity.¹ As such, the study had co-primary end points of MRD rate of conversion from negative to positive following lenalidomide discontinuation, as well as TFS among patients who discontinued maintenance. Bone marrow MRD status was evaluated by next generation flow cytometry at baseline and every 6 months thereafter.

Secondary end points included the rate of progression after lenalidomide discontinuation, rate of progression after re-administration of lenalidomide in cases of MRD positivity, progression-free survival, overall survival, and adverse events. In the event of disease progression, patients exited the study and started second-line treatment.

DISCLOSURES: Malandrakis declared receiving honoraria from Johnson & Johnson.

REFERENCES:

1. Malandrakis, P. Sustained marrow and imaging MRD negativity can lead to lenalidomide discontinuation following ASCT in multiple myeloma: Updated results from a prospective cohort study. Presented at: ESMO 2025 Congress; October 17–21, 2025; Berlin Germany. Abstract 1242O.

2. Terpos E, Malandrakis P, Ntanasis-Stathopoulos I, et al. Sustained bone marrow and imaging MRD negativity for 3 years drives discontinuation of maintenance post-ASCT in myeloma. Blood. 2025;145(20):2353‑2360. doi:10.1182/blood.2024027686