New EHA/EMN treatment guidelines for MM

During EHA 2025, an entire session was dedicated to the presentation of the updated treatment guidelines for patients with multiple myeloma (MM) developed in a collaborative effort by the Europan Hematology Association (EHA) and the European Myeloma Network (EMN). In the meantime, these updated guidelines have also been accepted for publication in Nature Reviews Clinical Oncology with Prof Evangelos Terpos and Prof Meletios Dimopoulos as first authors. In this video, Prof Michel Delforge (University Hospitals Leuven) talks us through the most important changes in these updated guidelines relative to the previous edition released in 2021.

For patients with transplant-eligible newly diagnosed multiple myeloma (NDMM), the recommended first-line treatment regimens according to the 2021 guidelines consisted of bortezomib-lenalidomide-dexamethasone (VRd) or daratumumab-bortezomib-thalidomide-dexamethasone (dara-VTD). In the updated guidelines, however, a shift was made to the use of quadruplets in first line (i.e., dara-VRd, or isatuximab-VRd [sa]-VRd). Another change in this setting consists of lenalidomide-daratumumab as an alternative to lenalidomide monotherapy as maintenance therapy after an autologous stem cell transplantation (ASCT). Quadruplet regimens have also entered the treatment paradigm for transplant ineligible NDMM patients. In these patients, the results of the CEPHEUS and IMROZ studies provide the basis to respectively recommend dara-VRd and Isa-VRd as first line options. As these studies had an upper age limit of 80 years, dara-Rd (DRd) was kept in the guidelines as a first line treatment option for older transplant-inelgible NDMM patients. For very frail patients, the guidelines propose a combination of daratumumab-lenalidomide and just 2 cylces of dexamethasone as a potential first line treatment.

For patients suffering a relapse after a first line treatment, the situation is becoming increasingly complex.  Previously, the first quesion to ask was whether patients were lenalidomide refractory. Nowadays, however, the first question should be if the patient is daraumumab refractory. Subsequently, the treatment choice is based on the refractoriness of patients to lenalidomide, or bortezomib. For patients who are lenalidomide refractory (and double-exposed), the new treatment guidelines see CAR-T therapy with ciltacabtagene autoleucel (cilta-cel) as the preferred second line treatment. Since May 1st 2025 this option is also available in Belgium in this setting. For patients who are not lenalidomide refractory, or double-exposed or for CAR-T inelgible patients, the guidelines see the belantamab mafodotin (bela)-based regimens bela-Vd and bela-Pd as good 2nd line treatment options. 

In the relapsed/refractory (RRMM) setting (i.e., patients who suffered multiple relapses), the updated EHA/EMN guidelines see a prominent role for bisepcific antibodies, such as teclistamab, elranatamab and talquetamab. In Belgium we are in a privileged position as all three of these bispecific antibodies are reimbursed for the treatment of triple-class refractory MM patients.

In brief, the 2025 EHA/EMN guidelines for MM establish quadruplet regimens in the first line treatment, irrespective of transplant elgibility, and acknowledge the benefit of dual maintenance therapy following an ASCT. In the relapsed setting, cilta-cel has become a preferred option as of second line, with bela-based regimens as a viable alternative in CAR-ineligible patients. In futher treatment lines, bispecific antibodies have become the new recommended standard.