In June 2026 local time, the European Hematology Association (EHA) Annual Congress was grandly held. In the Multiple Myeloma (MM) session, top global hematology experts engaged in in-depth dialogues regarding the treatment pathways for newly diagnosed multiple myeloma (NDMM), liquid biopsy for prognostic assessment, and intensified treatment regimens for ultra-high risk patients. This session was chaired by Professor Pieter Sonneveld from the Erasmus University Medical Center (Erasmus MC) in the Netherlands. It covered core topics such as the value of autologous stem cell transplantation (ASCT) in the era of quadruplet regimens, the clinical application of circulating tumor cells (CTC), and precision strikes for ultra-high risk patients.01 Navigating the Frontier: Evolution of NDMM Treatment Guidelines and the Reshaping of ASCT’s Role
At the beginning of the meeting, Professor Francesca Gay from the Department of Hematology, University of Turin, Italy, provided an in-depth interpretation of the “Status of ASCT in the context of quadruplet regimens.” Professor Gay pointed out that with the publication of the 2025 version of the MM treatment guidelines, quadruplet regimens containing anti-CD38 monoclonal antibodies have become the standard induction treatment strategy for NDMM, prompting the academic community to re-examine the benefit space of ASCT.
1.1 Efficacy Leap in the Quadruplet Era: Inspirations from the PERSEUS and CEPHEUS Studies
Professor Gay compared the data from the PERSEUS study for transplant-eligible (TE) patients and the CEPHEUS study for transplant-ineligible (TIE) patients. • PERSEUS Study: Utilized Dara-VRd (Daratumumab, Bortezomib, Lenalidomide, Dexamethasone) followed by ASCT and Dara-Len maintenance. The latest analysis shows that the estimated median progression-free survival (PFS) for patients under this regimen could reach 17 years. • CEPHEUS Study: Applied Dara-VRd in TIE patients. Data showed that even without transplantation, the estimated median PFS reached 8 years. Professor Gay emphasized that although cross-study comparisons should be made with caution, the huge difference in PFS data (17 years vs. 8 years) suggests that in the quadruplet era, ASCT as a consolidation therapy still holds irreplaceable value for further deep remission and prolonged survival.
1.2 “Grey Zones” and Stratified Decision-making: Frailty Assessment and MRD-driven Strategies
For “grey zone” patients aged between 65-70 in clinical practice, Professor Gay proposed recommendations for dynamic assessment. • Frailty Assessment: The IMWG frailty score should be used to distinguish between Fit, Unfit, and Frail patients. Studies show that Fit/Unfit patients under the age of 70 can still benefit from ASCT, while it is not recommended for Frail patients. • MIDAS Study and MRD-driven Strategy: Professor Gay conducted an in-depth analysis of the MIDAS study. This study explored whether to perform ASCT based on minimal residual disease (MRD) status after induction therapy. Preliminary data show that for patients who achieve MRD negativity, there is no significant difference in the MRD negativity rate between ASCT and quadruplet consolidation; however, Professor Gay pointed out that the durability of MRD is the key. Currently, it is still recommended to adhere to ASCT for high-risk and MRD-persistently positive patients, or even consider tandem ASCT.
02 New Prognostic Benchmark: Application of Circulating Tumor Cells (CTC) in Plasma Cell Diseases
Professor Bruno Paiva from the Department of Hematology, University of Navarra, Spain, focused on the theme “CTC: More than just a prognostic factor,” sharing breakthroughs in liquid biopsy for the entire disease course management of MM.
2.1 Biological Mechanisms: CTC as an Indicator of Extramedullary Escape
Professor Paiva pointed out that the quantity of CTCs is not only a reflection of tumor burden but also a biological indicator of tumor cell proliferation, microenvironment niche saturation, and extramedullary dissemination capability. Through transcriptomic analysis of paired bone marrow and peripheral blood samples, it was found that genetic alterations such as 1q21 amplification are closely related to the formation of CTCs.
2.2 Clinical Threshold Definition and Risk Stratification
Based on large-scale data from multiple international collaborative groups, Professor Paiva proposed data-driven CTC cutoff values: • MGUS/SMM Stage: Detection of CTCs is associated with an 8-fold increased risk of transformation to active MM. If CTC >0.2%, even if clinically classified as SMM, the outcome is no different from active MM. • Active MM Stage: 0.02% was identified as a threshold with independent prognostic significance. • Redefining Plasma Cell Leukemia (PCL): NDMM patients with CTC >2% have a prognosis consistent with primary plasma cell leukemia.
2.3 Peripheral Residual Disease (PRD) Monitoring: Can it Replace Bone Marrow Monitoring?
Professor Paiva introduced a new method called BloodFlow, which combines immunomagnetic enrichment with next-generation flow cytometry (NGF), achieving detection sensitivity of 10⁻⁷ to 10⁻⁸. • Data Consistency: The concordance between PRD detection and bone marrow MRD is approximately 78%. • Clinical Significance: During the maintenance phase, PRD positivity monitored by BloodFlow is a strong signal of imminent disease progression (a 15-fold increase in risk). Professor Paiva suggested that in the future, the frequency of bone marrow aspiration could be reduced, and more patient-friendly monitoring could be achieved through more frequent peripheral blood PRD testing.
03 Breaking the Deadlock: Precision Strikes for Ultra-High Risk (UHR) Myeloma
Professor Martin Kaiser from the Institute of Cancer Research (ICR) in London, UK, shared insights on the “Diagnostic and Therapeutic Challenges of Ultra-High Risk Myeloma,” directly addressing the most difficult points in current treatment.
3.1 Diagnostic Gap: Why is Traditional Staging Not Precise Enough?
Professor Kaiser emphasized that relying solely on genetic alterations (such as R-ISS staging) misses about 40% of “functional high-risk” patients. He proposed integrating Gene Expression Profiling (GEP) analysis. Data show that combining traditional genetics with GEP can reduce the proportion of “unexplained early recurrence” from 40% to below 20%.
3.2 Optimum MUKnine Study: A Successful Paradigm of Intensified Treatment
Professor Kaiser detailed the long-term follow-up results of the Optimum MUKnine study. The study employed an extremely aggressive regimen for UHR patients: Dara-CVRd (Cyclophosphamide combined with quadruplet) induction, ASCT, 18 months of Dara-VRd consolidation, followed by Dara-Len doublet maintenance. • Key Data: For “Double-hit” patients, the 5-year PFS rate of this regimen was significantly higher than traditional regimens, avoiding the cliff-like recurrence previously seen around 36 months. • Precision Benefit Population: Subgroup analysis showed that patients with “Double-hit” and high-risk GEP benefited the most; while “Triple-hit” patients or those with plasma cell leukemia features remain the focus of future efforts.
3.3 The Entry of Immunotherapy
In the Q&A session, Professor Kaiser expressed expectations regarding whether UHR patients should use bispecific antibodies or CAR-T therapy earlier. He noted that ongoing studies such as TECK-4 are exploring the first-line application of such immunotherapies. For UHR patients with extreme genetic instability, traditional chemo-immunotherapy may not be sufficient to maintain long-term remission, and immune remodeling might be the only way out.
04 Expert Dialogue: Extraction of Clinical Hot Topic Q&A
Under the moderation of Professor Sonneveld, a heated discussion took place on-site. The following are extracts of key topics: Q1: For high-risk patients, is tandem ASCT still recommended after ASCT? Professor Gay: In the quadruplet regimen era, if a patient does not achieve deep remission after induction, tandem ASCT remains a consideration for high-risk patients (such as those with 17p deletion or 11;14 translocation who have a poor response to induction).
Q2: Can CTC detection guide the discontinuation of maintenance therapy?
Professor Paiva: Currently, treatment cannot be discontinued based solely on CTC negativity. The BloodFlow method is being validated; it will only be safer to discuss discontinuation when a patient is negative for bone marrow MRD and has sustained PRD negativity in peripheral blood.
Q3: How to manage UHR patients with TP53 mutation or deletion?
Professor Kaiser: Such patients are currently the biggest challenge, as their MRD negativity duration is extremely short. Our current strategy is ultra-intensified consolidation therapy. In the future, combining targets for the TP53 pathway or early intervention with cell therapy are research priorities.
Conclusion: Towards Individualized Precision Treatment in 2026
In his summary, Professor Sonneveld pointed out that MM treatment is no longer a simple stacking of regimens, but has entered an era of precision titration based on patient frailty, tumor genetic characteristics, GEP profiles, and dynamic MRD/CTC status. • ASCT: Remains the cornerstone for TE patients to cross the peak of survival. • CTC: Will become a more sensitive risk stratification tool than traditional staging. • UHR Patients: Intensified consolidation and maintenance strategies (such as the Optimum model) have begun to show results.
The core message delivered by this congress is clear: through more precise diagnosis (Precision Diagnostics) to achieve more precise treatment (Precision Medicine), we are allowing MM patients, especially that most difficult-to-treat ultra-high risk population, to see the dawn of long-term survival or even a cure.
