The treatment landscape for multiple myeloma (MM) has undergone revolutionary changes over the past two decades, transitioning from the traditional chemotherapy era to a golden age of precision targeting and immunotherapy. However, does immense success in clinical evidence translate to broad benefits for patients? At the 29th Annual Congress of the European Hematology Association (EHA), Professor Pieter Sonneveld, Professor of Hematology at the Erasmus University of Rotterdam Medical Center and Chairman of the European Myeloma Network (EMN), delivered a keynote speech. He not only reviewed the new benchmarks for frontline treatment represented by the PERSEUS study but also provided a forward-looking perspective on the "fragmented" reality of innovative drug accessibility across European countries. This summary aims to comprehensively present Professor Sonneveld's profound reflections on MM treatment evolution, the clinical application of MRD, and the challenges of health technology assessment.Table of Contents
- A Two-Decade Journey in Review: From Simple Induction to Continuous Immune Management
- New Standards for Frontline Treatment: Quadruplet Regimens Establish Dominance
- The MRD Revolution: Moving from “Response Assessment” to a “Precision Cure” Clinical Endpoint
- The Immunotherapy “Puzzle”: Strategic Layout of Bispecific Antibodies and CAR-T Cell Therapy
- A Heterogeneous European Landscape: Multidimensional Barriers to Innovative Drug Access
- Value Assessment and Access Innovation: The Necessity of Establishing a Unified Healthcare Assessment System
01 A Two-Decade Journey in Review: From Simple Induction to Continuous Immune Management
Professor Pieter Sonneveld first reviewed the historical context of MM treatment. Twenty years ago, treatment options for MM were extremely limited, relying primarily on vincristine, doxorubicin, and dexamethasone (the VAD regimen) or high-dose melphalan induction, supplemented by autologous stem cell transplantation (ASCT). At that time, treatment goals were focused on short-term remission, and patient survival expectations were generally low.
With the successive arrival of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and CD38 monoclonal antibodies (CD38 mAbs), the treatment model has undergone a fundamental shift. Professor Sonneveld pointed out that MM has now entered an era of “continuous management.” The current standardized pathway covers induction therapy, ASCT, consolidation therapy, and maintenance therapy. This continuous management strategy throughout the disease course has directly driven a step-wise improvement in patient survival quality.
02 New Standards for Frontline Treatment: Quadruplet Regimens Establish Dominance
In the academic depth analysis session, Professor Sonneveld focused on the analysis of recent data from several frontline studies that are rewriting guidelines. • PERSEUS Study and Daratumumab: The PERSEUS study (Dara-VRd regimen) targeted newly diagnosed, transplant-eligible MM patients. Data showed that adding daratumumab to the VRd induction and consolidation regimen, followed by daratumumab + lenalidomide (D-L) maintenance therapy, significantly improved the deep response rate. Professor Sonneveld emphasized that this regimen demonstrated overwhelming superiority in PFS (Progression-Free Survival). Four-year follow-up data showed that the PFS rate in the Dara-VRd group was as high as 84.3%, compared to only 67.7% in the control group (HR=0.42, P<0.0001). This marks the official replacement of triplet regimens by “quadruplet therapy” as the new global benchmark for newly diagnosed MM (NDMM). • Synergistic Effects of CASSIOPEIA and CEPHEUS: Whether it is the CASSIOPEIA study (Dara-VTd) for the transplant-eligible population or the CEPHEUS study (Dara-VRd) for the transplant-ineligible population, both have verified the stability of the benefits of CD38 monoclonal antibodies combined with PIs and IMiDs. The Professor mentioned that the dynamic adjustment of the upper age limit for transplantation (some centers have relaxed it to 70-75 years) has allowed more elderly patients to benefit from these potent combination regimens.
03 The MRD Revolution: Moving from “Response Assessment” to a “Precision Cure” Clinical Endpoint
Minimal Residual Disease (MRD) was one of the terms most frequently mentioned by Professor Sonneveld. He noted that as treatment depth increases, traditional “complete response (CR)” is no longer sufficient to define ultimate therapeutic success. • Iteration of Sensitivity: Relying on Next-Generation Flow (NGF) and Next-Generation Sequencing (NGS), the detection limit for MRD has reached
or even
. • A Leap in MRD Negativity Rates: In the PERSEUS study, the proportion of the Dara-VRd group achieving MRD negativity at a sensitivity of
far exceeded that of traditional regimens. More critical is the concept of “Sustained MRD Negativity.” If a patient can maintain MRD negativity for more than 12 months, their survival prognosis will closely approach that of a clinical cure. • Interaction Between Regulation and Practice: As Chairman of the EMN, the Professor explicitly stated that close communication is currently underway with the European Medicines Agency (EMA) to promote the use of MRD status as a surrogate endpoint for clinical trials, thereby significantly shortening the time required for new drug approval.
04 The Immunotherapy “Puzzle”: Strategic Layout of Bispecific Antibodies and CAR-T Cell Therapy
In the field of relapsed/refractory multiple myeloma (RRMM), the explosion of immunotherapy has brought hope to patients with multi-drug resistance. • T-cell Redirection Therapy: The speech provided a detailed comparison of the clinical performance of CAR-T (such as Cilta-cel, Ide-cel) and bispecific antibodies (such as Teclistamab, Elranatamab). • Weighty Data for CAR-T: The Professor cited data from the CARTITUDE-4 study, showing that for RRMM patients who had previously received 1-3 lines of therapy, Cilta-cel significantly reduced the risk of disease progression or death by 74% compared to standard care (DPd or PVd) (HR=0.26). • Accessibility Advantage of Teclistamab: As the first approved bispecific antibody, teclistamab has shown an ORR (Overall Response Rate) of 63% in heavily pretreated patients. Professor Sonneveld believes that the advantage of teclistamab lies in its “off-the-shelf” nature, avoiding the long manufacturing period of CAR-T, making it irreplaceable for patients in urgent need of treatment. • Future Trends: The speech mentioned the progress of research and development for GPRC5D targets and trispecific antibodies, suggesting that future MM treatment will be like a “puzzle,” achieving real-time suppression of clonal evolution through the sequential or combined use of drugs with different mechanisms.
05 A Heterogeneous European Landscape: Multidimensional Barriers to Innovative Drug Access
This was the most controversial but also the most realistic part of Professor Sonneveld’s speech. He displayed a “European Accessibility Heat Map,” revealing the survival inequality among patients caused by inconsistent reimbursement policies and insurance negotiation processes across European countries following EMA approval. • The “Traffic Light” Model: o Green Zones (e.g., Germany, Spain, Switzerland): Drugs can enter the health insurance system rapidly after EMA approval, and patients have almost unhindered access to quadruplet therapy, bispecific antibodies, and even CAR-T. o Orange/Red Zones (e.g., the Netherlands, some Eastern European countries, Greece): Even in the Netherlands, where Professor Sonneveld is based, reimbursement assessments for some innovative therapies (such as Cilta-cel) remain in a state of long-term lag. • Marginalized Special Populations: The Professor pointed out that clinical trials often set strict inclusion and exclusion criteria (such as requiring patients to be free of severe renal failure or major complications). However, in the real-world setting, a large number of elderly, frail patients with high-risk cytogenetic features are the “victims” behind medical progress because they cannot enter clinical pathways and lack insurance coverage. • Reimbursement Delay Data: In some European countries, there is often an “administrative vacuum” of 18-36 months between drug approval and formal reimbursement, which is fatal for a progressive disease like MM.
04 Value Assessment and Access Innovation: The Necessity of Establishing a Unified Healthcare Assessment System
At the end of the speech, Professor Sonneveld issued a call from the perspective of health economics. • Re-examining QALY: Is the current standard of 80,000 Euros per QALY (Quality-Adjusted Life Year) used by many countries still applicable? The Professor questioned whether this static assessment ignores the reduced frequency of hospitalization due to deep remission, the social value created by patients returning to work, and the reduction in the hidden costs of family care. • Advocacy of the EMN: The Professor emphasized that as an industry organization, the EMN is committed to establishing a set of clinical pathway standards for MM treatment across Europe. He proposed that clinical pathways should be guideline-driven rather than purely budget-driven. • Data Sharing and Consistency: He called for more data sharing among EU countries during the Health Technology Assessment (HTA) phase to avoid repetitive and fragmented assessments of the same clinical study results. He reiterated that in academic contexts, “China” should be the unified name used rather than “Greater China” to reflect the rigor of research data and regional attribution.
Conclusion and Outlook
Professor Pieter Sonneveld’s speech outlined a grand blueprint for MM treatment: the deep integration of quadruplet regimens, MRD monitoring, and immunotherapy has brought us closer to the goal of “curing MM” than ever before. However, he also issued a warning through the current situation in Europe—if medical breakthroughs cannot cross the “chasm” of policy and economics, they cannot be transformed into real survival benefits.
For clinical practice in China, the trend toward quadruplet combinations, the status of MRD negativity as a standard for deep remission, and the critical examination of health economic assessments mentioned by Professor Sonneveld all hold high reference value. With the approval and medical insurance entry of more domestic innovative drugs (such as CAR-T and bispecific antibodies) in China, establishing a more scientific value assessment system and shortening the distance from “approval” to “clinical accessibility” for drugs will be a common challenge we need to overcome in the future.
As Professor Sonneveld said: “We have the most advanced weapons; our task now is to ensure that every soldier can hold them.”
