Regulatory approval of 14 new drugs and treatment regimens for multiple myeloma alongside other recent advances in care has triggered a significant shake-up of European guidelines on diagnosing and managing patients with the condition.
The new European Haematology Association (EHA) and European Myeloma Network (EMN) guidelines, which replace the previous version published in 2021, also include for the first time the R2-ISS staging system for the first time and recommendations on new prognostic factors.
A multidisciplinary group reviewed new evidence from January 2021 until May 2025 to develop new recommendations and clinical algorithms for newly diagnosed and relapsed/refractory MM, as well as smouldering MM (SMM).
“In these guidelines, the panel provides useful recommendations for the diagnosis, follow-up and treatment of patients with MM in different clinical scenarios, such as disease refractory to both anti-CD38 antibodies and lenalidomide, or with four-class refractoriness, to name a few,” the authors noted.
“The experts also agree that the high efficacy of novel therapeutic agents creates the need for new response criteria that will lead to therapeutic decisions, such as when to stop maintenance or when to change therapy to achieve the best results in patients,” they highlighted.
Within the guidelines, published in Nature Reviews Clinical Oncology [link here], the diagnosis criteria for MM and SMM remain unchanged from the previous guidelines, but the increasing use of the Second Revision of the International Staging System (R2-ISS), developed in 2022, was noted.
In addition, the guidelines now recommend assessing disease features from the 2024 definition of high-risk MM, published by The International Myeloma Society and the International Myeloma Working Group, which “will influence disease staging and prognostication in the near future”, the group said.
The authors also highlighted that measuring circulating plasma cell levels, evaluating monoclonal protein via mass spectrometry, and gene expression profiling “could soon change the routine management of patients.”
New treatments and regimens
For SMM, the guidelines still back a watch-and-wait approach for low- and intermediate-risk patients, but advise considering daratumumab monotherapy for high-risk SMM, which has recently been backed for approval in Europe in this setting.
In newly diagnosed MM, DaraVRd (daratumumab, bortezomib, lenalidomide and dexamethasone) and IsaVRd (isatuximab, bortezomib, lenalidomide and dexamethasone) are now recommended as induction therapy prior to autologous stem cell transplant (ASCT), with DaraVTd (daratumumab, bortezomib, thalidomide and dexamethasone) included as an alternative option.
For maintenance treatment after ASCT, clinicians are now advised to use daratumumab as well as lenalidomide, after the combination demonstrated superior progression-free survival in the long-term, randomised PERSEUS trial.
Also among the new recommendations, IsaVRd and DaraVRd are backed for frail newly diagnosed MM patients who are not eligible for ASCT.
For relapsed/refractory MM, BelaVd (belantamab mafodotin, bortezomib and dexamethasone) is recommended for patients who have received one to three lines of therapy, while Selinexor is also newly approved and recommended in some clinical scenarios.
Two new CAR T cell therapies – ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) – have now been approved in the UK, with cilta-cel recommended as a second-line treatment in patients with disease refractory to lenalidomide, or refractory to lenalidomide and bortezomib.
Both CAR T cell products are recommended as options for third- or fourth-line treatment of patients with triple-class refractory MM.
Read the guidelines in full here