Since the publication in 2021 of the European Hematology Association (EHA) Clinical Practice Guidelines for the treatment of patients with smouldering multiple myeloma (SMM) and multiple myeloma (MM), developed in collaboration with the European Society for Medical Oncology, a novel international staging system (R2-ISS) has been developed, several prognostic factors are entering clinical practice (such as minimal residual disease, circulating plasma cells and monoclonal protein assessed by mass spectrometry) and, at the time of writing, 14 novel regimens have been approved by the EMA and/or the FDA for the treatment of patients with MM. A multidisciplinary group of experts from the EHA and European Myeloma Network, based in various institutions mostly located in Europe, have updated the previous guidelines and produced algorithms for everyday clinical practice that incorporate levels of evidence and grades of recommendation based on the aforementioned new data. In these Evidence-Based Guidelines, we provide key treatment recommendations for both patients with newly diagnosed MM and those with relapsed and/or refractory MM, including guidance for the use of established drugs as well as contemporary immunotherapies. Novel approaches for the management of patients with SMM focus on those who might require early intervention. Finally, we provide recommendations for myeloma-related complications and adverse events, such as bone disease, renal impairment and infections, as well as for those associated with T cell-mobilizing therapies, such as cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome.

• MeSH
• Humans MeSH
• Evidence-Based Medicine MeSH
• Multiple Myeloma * diagnosis   therapy   MeSH
• Practice Guidelines as Topic * MeSH
• Neoplasm Staging MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

In the post-pandemic COVID-19 period, human activities have returned to normal and COVID-19 cases are usually mild. However, patients with multiple myeloma (MM) present an increased risk for breakthrough infections and severe COVID-19 outcomes, including hospitalization and death. The European Myeloma Network has provided an expert consensus to guide patient management in this era. Vaccination with variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4/5 strains, is essential as novel strains emerge and become dominant in the community. Boosters should be administered every 6-12 months after the last vaccine shot or documented COVID-19 infection (hybrid immunity). Booster shots seem to overcome the negative effect of anti-CD38 monoclonal antibodies on humoral responses; however, anti-BCMA treatment remains an adverse predictive factor for humoral immune response. Evaluation of the immune response after vaccination may identify a particularly vulnerable subset of patients who may need additional boosters, prophylactic therapies and prevention measures. Pre-exposure prophylaxis with tixagevimab/cilgavimab is not effective against the new dominant variants and thus is no longer recommended. Oral antivirals (nirmatrelvir/ritonavir and molnupiravir) and remdesivir are effective against Omicron subvariants BA.2.12.1, BA.4, BA.5, BQ.1.1 and/or XBB.1.5 and should be administered in MM patients at the time of a positive COVID-19 test or within 5 days post symptoms onset. Convalescent plasma seems to have low value in the post-pandemic era. Prevention measures during SARS-CoV-2 outbreaks, including mask wearing and avoiding crowded places, seem prudent to continue for MM patients.

• MeSH
• COVID-19 * epidemiology   MeSH
• Consensus MeSH
• Humans MeSH
• Multiple Myeloma * therapy   MeSH
• Antibodies, Neutralizing MeSH
• Pandemics MeSH
• SARS-CoV-2 MeSH
• COVID-19 Serotherapy MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Antibodies, Neutralizing MeSH

Multiple myeloma (MM) is a hematological malignancy caused by the clonal expansion of plasma cells. The incidence of MM worldwide is increasing with greater than 140 000 people being diagnosed with MM per year. Whereas 5-year survival after a diagnosis of MM has improved from 28% in 1975 to 56% in 2012, the disease remains essentially incurable. In this review, we summarize our current understanding of MM including its epidemiology, genetics and biology. We will also provide an overview of MM management that has led to improvements in survival, including recent changes to diagnosis and therapies. Areas of unmet need include the management of patients with high-risk MM, those with reduced performance status and those refractory to standard therapies. Ongoing research into the biology and early detection of MM as well as the development of novel therapies, such as immunotherapies, has the potential to influence MM practice in the future.

• Keywords
• clinical presentation, plasma cell disease, risks factors, survival, treatment,
• MeSH
• Cyclin D1 genetics   MeSH
• Exosome Multienzyme Ribonuclease Complex genetics   MeSH
• Genetic Predisposition to Disease MeSH
• Histone Demethylases genetics   MeSH
• Immunotherapy methods   MeSH
• Humans MeSH
• Survival Rate MeSH
• Multiple Myeloma diagnosis   epidemiology   genetics   therapy   MeSH
• Mutation MeSH
• Biomarkers, Tumor genetics   MeSH
• Plasma Cells immunology   pathology   MeSH
• Repressor Proteins genetics   MeSH
• Risk Factors MeSH
• Transcriptional Elongation Factors genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• CCND1 protein, human MeSH Browser
• CDCA7L protein, human MeSH Browser
• Cyclin D1 MeSH
• DIS3 protein, human MeSH Browser
• ELL2 protein, human MeSH Browser
• Exosome Multienzyme Ribonuclease Complex MeSH
• Histone Demethylases MeSH
• KDM1A protein, human MeSH Browser
• Biomarkers, Tumor MeSH
• Repressor Proteins MeSH
• Transcriptional Elongation Factors MeSH

Multiple myeloma is the second most common hematologic malignancy. Current treatment strategies are mainly based on immunomodulatory drugs, proteasome inhibitors or combination of both. Novel agents added to these backbone treatments represent a promising strategy in treatment of newly diagnosed as well as relapsed and refractory multiple myeloma patients. In this respect, the incorporation of monoclonal antibodies into standard-of-care regimens markedly improved prognosis of myeloma patients during the last years. More specifically, monoclonal anti-CD38 antibodies, daratumumab and isatuximab, have been implemented into treatment strategies from first-line treatment to refractory disease. In addition, the monoclonal anti-SLAM-F7 antibody elotuzumab in combination with immunomodulatory drugs has improved the clinical outcomes of patients with relapsed/refractory disease. Belantamab mafodotin is the first approved antibody drug conjugate directed against B cell maturation antigen and is currently used as a monotherapy for patients with advanced disease. This review focuses on clinical efficacy and safety of monoclonal antibodies as well as antibody drug conjugates in multiple myeloma.

• Keywords
• antibody drug conjugates, monoclonal antibodies, multiple myeloma,
• Publication type
• Journal Article MeSH
• Review MeSH