Updated recommendations for the management of patients with MM: EHA-EMN evidence-based guidelines

The European Hematology Association (EHA) and European Myeloma Network (EMN) have published updated evidence-based guidelines for the diagnosis, treatment, and follow-up of multiple myeloma, building on the 2021 EHA–ESMO recommendations, in Nature Reviews Clinical Oncology.

The 2025 revision incorporates advances across the field, including in prognostic assessment, expanded use of measurable residual disease to inform treatment, the adoption of quadruplet induction regimens as new standards, evolving management of high-risk smoldering multiple myeloma, earlier use of immunotherapies in relapsed/refractory disease, and care and management of patients with complications.

Key learnings

Risk assessment recommendations have been updated to the R2-ISS, with high-risk criteria now incorporating cytogenetics, biochemical markers, and emerging tools such as circulating plasma cell quantification and mass spectrometry.

Sustained MRD negativity is now recognized as a regulatory trial endpoint and is increasingly used to guide treatment decisions, with PET-CT and diffusion-weighted MRI recommended alongside bone marrow testing to determine MRD status.

Quadruplet regimens are emerging as the new standard for first-line therapy, with DaraVRd and IsaVRd preferred for many newly diagnosed patients and daratumumab + lenalidomide maintenance replacing lenalidomide alone after transplant.

Immunotherapies are being applied earlier in the treatment of relapsed/refractory multiple myeloma, with CAR T-cell therapies, bispecific antibodies, and antibody–drug conjugates increasingly used in earlier lines of therapy and treatment choices individualized based on prior treatment exposure and refractoriness.

Patients with high-risk smoldering MM may benefit from early treatment, with evidence supporting daratumumab monotherapy to delay disease progression and improve survival, although regulatory approval was pending at the time of publication.