At the 2025 Annual Congress of the European Hematology Association (EHA), the much-anticipated updated EHA-EMN clinical practice guidelines for multiple myeloma (MM) were officially released. Covering key areas such as diagnostic assessment, risk stratification, treatment pathways, and follow-up management, the new guidelines provide more forward-thinking and practical guidance for clinical implementation.To offer deeper insight into the core updates, Oncology Frontier – Hematology Frontier invited Professor Evangelos Terpos, one of the guideline’s lead authors from the National and Kapodistrian University of Athens, for an exclusive interview. He discussed the major changes in testing parameters, imaging techniques, and therapeutic strategies, along with their clinical significance.
Oncology Frontier – Hematology Frontier: In your view, which new diagnostic criteria or biomarkers introduced in the 2025 EHA-EMN guidelines are most impactful for early and accurate diagnosis and risk stratification in MM?
Professor Evangelos Terpos: The updated EHA-EMN guidelines bring several important changes regarding how we obtain critical information from bone marrow, blood, and urine testing for the diagnosis and follow-up of multiple myeloma.
In terms of urine testing, the new guidelines now recommend performing urine protein electrophoresis and 24-hour urine protein quantification at the time of diagnosis and relapse to determine light chain secretion. However, during the follow-up period, serum free light chain (sFLC) testing can be used instead of 24-hour urine collection. sFLC offers higher sensitivity and is sufficient to evaluate treatment response, which is why routine 24-hour urine testing is no longer recommended during follow-up.
Regarding bone marrow assessment, the updated guidelines suggest going beyond traditional FISH analysis by incorporating screening for additional genetic abnormalities linked to high-risk prognosis. In addition to the previously included translocations t(4;14), t(14;16), and t(14;20), the updated recommendations now include evaluation of gain of 1q copy number (whether acquired or amplified), deletion of 1p32 (monoallelic or biallelic), and TP53 mutations. In patients with normal creatinine levels, the evaluation should also take into account β2-microglobulin levels. These markers are in alignment with the most recent definitions of high-risk myeloma from the International Myeloma Working Group (IMWG) and the International Myeloma Society (IMS), and are therefore of great clinical relevance.
The guidelines also highlight a new direction in imaging evaluation. Diffusion-weighted MRI (DWI-MRI) is recommended as a functional imaging tool to assess minimal residual disease (MRD) negativity. DWI-MRI has the potential to partly replace PET-CT in this context. It is recommended that DWI-MRI be performed both before treatment and once MRD negativity is achieved.
Lastly, MRD negativity remains a central focus of the updated guidelines. It continues to serve as a key factor in predicting prognosis for patients who achieve complete remission, and it is expected to become increasingly important in guiding personalized treatment decisions in the future.
Oncology Frontier – Hematology Frontier: How do you view the updated guideline recommendations on patient follow-up and the management of treatment resistance? Do you foresee a greater integration of personalized monitoring and dynamic therapy adjustment in future clinical practice?
Professor Evangelos Terpos: As I mentioned earlier, we are actively working on establishing a treatment framework that stratifies patients based on their prior resistance to specific therapies. However, I believe it’s important to acknowledge the inherent complexity clinicians face when treating each patient. Every individual presents a unique clinical picture—some may have comorbidities, frailty, drug resistance, or a history of severe adverse reactions to particular drug classes. In this context, expecting a “one-size-fits-all” answer is simply not realistic.
That’s where the true value of guidelines lies: they offer a foundational reference, but the final treatment decision must be individualized and adaptable to each patient’s specific condition. Especially now, with so many therapeutic options available, determining the optimal sequence of treatments has become one of the most challenging tasks in myeloma care. Currently, we have two CAR-T products, three BCMA-targeted bispecific antibodies, and one BCMA-targeted antibody-drug conjugate—belantamab mafodotin.
So which should be used first? The answer depends entirely on the patient. For instance, in a second-line setting, if the patient is refractory to both daratumumab and lenalidomide but remains in good physical condition and is eligible for CAR-T therapy, then cilta-cel may be the optimal choice. On the other hand, for patients who are not candidates for or cannot access CAR-T, the combination of belantamab mafodotin with pomalidomide and dexamethasone could represent a more practical and effective option for that specific group.
We are also seeing an increasing number of special patient subtypes—those with high-risk disease, extramedullary involvement, or plasma cell leukemia. While the current therapies offer new opportunities for these populations, there is still a critical need for dedicated research to answer the pressing clinical questions associated with them.
Fortunately, we now have more therapeutic tools than ever before. I am confident that with the help of these innovative drugs, we can extend survival in high-risk populations—and in some cases, even achieve true remission or cure.
Professor Evangelos Terpos National and Kapodistrian University of Athens, Greece
Professor of Hematology and Director of the Stem Cell Transplantation Unit, Department of Clinical Therapeutics, National and Kapodistrian University of Athens Medical School.
His main research interests include the biological mechanisms and clinical management of bone disease in multiple myeloma, as well as the application of minimal residual disease (MRD) and circulating tumor cells (CTCs) in plasma cell malignancies.
He serves as the principal investigator (PI) in multiple clinical studies evaluating novel therapeutic agents—such as antibody-drug conjugates, CAR-T cell therapies, and bispecific antibodies—for the treatment of multiple myeloma.
