Advances in the diagnosis and management of multiple myeloma — current State of the art

Multiple myeloma (MM) is a malignant proliferation of monoclonal plasma cells, consistently preceded by monoclonal gammopathy of undetermined significance (MGUS) or smoldering MM. Advances in diagnostic criteria, including the 2022 World Health Organization (WHO) classification, have integrated morphological, immunophenotypic, cytogenetic, and molecular findings, alongside modern imaging modalities such as whole-body low-dose computed tomography (low-dose CT), positron emission tomography–computed tomography (PET-CT), and magnetic resonance imaging (MRI). Risk stratification has been refined by the revised International Staging System (R2-ISS), which incorporates cytogenetic abnormalities including del(17p), t(4;14), and 1p-/1q+. First-line therapy depends on eligibility for autologous hematopoietic stem cell transplantation (auto-HSCT). Induction regimens combining proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies are standard, with consolidation via auto-HSCT and maintenance therapy — typically lenalidomide — improving long-term outcomes. The management of relapsed/refractory MM (RRMM) increasingly relies on next-generation immunotherapies. Bispecific antibodies targeting BCMA/CD3 or GPRC5D/CD3, immunotoxins, and CAR-T cell therapies have demonstrated high response rates in heavily pretreated patients. Emerging trispecific antibodies, such as JNJ-79635322 (BCMA × GPRC5D × CD3), have shown remarkable efficacy with a favorable safety profile, offering potential for integration into earlier lines of therapy. Treatment of solitary plasmacytoma relies primarily on radiotherapy, with prognosis depending on lesion site. Palliative radiotherapy remains crucial for symptom control and prevention of skeletal complications in advanced disease. The therapeutic landscape of MM is shifting toward earlier use of potent immunotherapies, including CAR-T and trispecific antibodies, with the goal of achieving deeper and more durable remissions. Ongoing clinical trials will determine their optimal sequencing, leading to an increasing number of patients achieving a ‘functional’ cure — and possibly complete cure — in selected subsets.