The 2025 European Society for Medical Oncology (ESMO) Congress is set to take place in Berlin, bringing together leading experts and cutting-edge research from across oncology. In hematology, several studies are attracting particular attention, spanning mechanisms of CAR-T resistance, innovative dual-target therapies, MRD-guided treatment discontinuation in multiple myeloma, and single-cell profiling. Together, these advances highlight the rapid evolution of hematologic malignancy research and the growing potential for more precise, individualized treatment strategies.To highlight major advances in hematology and facilitate academic exchange, Oncology Frontier – Hematology Frontier has launched the “What Are the ESMO Experts Watching?” series. In this issue, Professor Chengcheng Fu from the First Affiliated Hospital of Soochow University provides an expert perspective on the innovation and clinical implications of a study exploring MRD-guided lenalidomide discontinuation in patients with multiple myeloma (MM), while also discussing potential future directions for the field.
Abstract 1242O: Sustained Bone Marrow and Imaging MRD Negativity May Guide Lenalidomide Discontinuation After Autologous Stem Cell Transplantation in Multiple Myeloma: Updated Results From a Prospective Cohort Study
Background
Lenalidomide maintenance following autologous stem cell transplantation (ASCT) remains a standard treatment strategy for eligible patients with newly diagnosed multiple myeloma. However, the optimal duration of maintenance therapy remains unclear.
Methods
This prospective study enrolled patients with newly diagnosed MM who underwent ASCT followed by lenalidomide maintenance therapy.
Patients underwent serial assessments of minimal residual disease (MRD). Those who achieved at least three consecutive negative bone marrow MRD assessments, had negative PET/CT findings, and had received at least 36 months of maintenance therapy discontinued lenalidomide.
MRD was subsequently assessed every six months. If a patient’s MRD status converted from negative to positive, lenalidomide maintenance was restarted.
Results
A total of 54 patients achieved MRD negativity and discontinued lenalidomide maintenance. The median age at MM diagnosis was 56 years (range, 39–66 years).
According to the revised International Staging System (R2ISS), 46.3% of patients had stage I disease, 27.8% stage II, 24.1% stage III, and 1.8% stage IV disease.
After a median follow-up of 41.3 months from treatment discontinuation, the landmark PFS rates at 1, 2, and 3 years were 96.3%, 96.3%, and 93.9%, respectively.
The 3-year treatment-free survival (TFS) rate was 75.7% (95% CI, 64.1%–89.5%), while the 1- and 2-year TFS rates were 96.2% and 89.9%, respectively.
Among patients whose MRD converted from negative to positive, the median time to MRD relapse was 30.6 months. Notably, patients who experienced MRD relapse still had a 3-year landmark PFS rate of 92.3%.
Overall, 14 patients (25.9%) who experienced MRD conversion after initially completing maintenance therapy restarted single-agent lenalidomide. Four patients (7.4%) subsequently experienced disease progression and required second-line treatment.
Among those who restarted lenalidomide, the median follow-up from treatment reinitiation was 13.4 months. For patients who progressed, the median time to progression from treatment reinitiation was 16 months.
Only one patient died during the treatment-free period, and the death was unrelated to MM.
Conclusions
Sustained MRD negativity following ASCT, together with completion of three years of lenalidomide maintenance, may provide a basis for safely discontinuing maintenance therapy in selected patients.
Expert Commentary
Professor Chengcheng Fu:
This prospective cohort study addresses a highly practical clinical question: Can lenalidomide maintenance be safely discontinued in patients with multiple myeloma who have undergone ASCT and achieved sustained MRD negativity at both the bone marrow molecular and imaging levels?
Previous research, including a study published by Evangelos Terpos and colleagues in Blood, has shown that following treatment discontinuation, most patients remained MRD-negative or experienced only limited MRD/imaging conversion, with treatment being restarted when necessary. These findings suggest that deep and sustained MRD negativity may serve as a clinically feasible biomarker for guiding treatment discontinuation.
The innovation of this study lies primarily in two aspects.
First, it combines bone marrow molecular MRD assessment with functional imaging using PET/CT to guide treatment discontinuation. This multimodal approach may help compensate for the limitations of relying on a single assessment modality.
Second, the study provides prospective evidence supporting the concept of “selective treatment discontinuation” and treatment-free remission. This strategy could potentially reduce long-term treatment-related toxicity and financial burden while improving patients’ quality of life.
For patients who have achieved a deep response, particularly those with poor treatment tolerance or a high risk of long-term complications, an individualized treatment-discontinuation strategy could help reduce unnecessary exposure to maintenance therapy.
From a broader perspective, this study is consistent with the growing trend toward MRD-driven precision management in multiple myeloma. Increasing numbers of clinical trials are exploring whether MRD can be used to guide treatment de-escalation or intensification, while efforts are also underway to standardize and integrate multimodal MRD assessment, including imaging, next-generation sequencing (NGS), and flow cytometry.
If validated in larger and randomized studies, an MRD-guided “stop–monitor–restart” treatment pathway could potentially become an additional treatment option in routine clinical practice.
Overall, this study provides valuable prospective evidence supporting MRD-guided individualized maintenance strategies in multiple myeloma. However, before this approach can be broadly incorporated into routine practice, higher-level evidence and standardized criteria for MRD assessment, treatment discontinuation, monitoring, and treatment reinitiation will still be required.
Professor Chengcheng Fu
