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Multiple myeloma is characterized by a wide clinical heterogeneity due to an intricate network of interactions between bone marrow-resident clonal plasma cells and the microenvironment. Over the last years, dramatic improvement in the understanding of these pathways led to the introduction of novel drugs with immune-mediated mechanisms of action. Some of these compounds, such as the anti-cd38 daratumumab and isatuximab, the anti-slamf-7 elotuzumab, and the antibody-drug conjugate belantamab-mafodotin, have been tested in large clinical trials and have now fully entered the real-life management. The bispecific T-cell engagers are under investigation with promising results, and other satisfactory data is expected from the application of nanotechnologies. The perfect timing to introduce these drugs in the sequence of treatment and their adverse events represent new challenges to be addressed, and further experience is required to improve their use.

Venous thromboembolism is a common complication of patients with hematologic malignancies, due both to release of procoagulant factors by tumor cells and to external factors, such us drugs. In multiple myeloma patients, the risk is increased by use of immunomodulants, especially when associated to multidrug therapy, during the induction phase. Prevention of venous thromboembolism in myeloma patients is highly recommended but specific guidelines are still lacking. The most common approach is to stratify the thrombotic risk according to individual, myeloma-related and therapy-related risk factors and to use aspirin for all patients, except those with two or more thrombotic risk factors who should be treated with traditional oral or parenteral anticoagulant. A more controversial approach indicates for prophylaxis either anticoagulant or aspirin, regardless of risk stratification. Recent trials investigate prophylaxis in myeloma patients with direct oral anticoagulants, based on studies showing efficacy and safety of this new class of drugs in the treatment and prophylaxis of thrombosis in patients with any malignancy. The results of these trials are encouraging but they need to be confirmed by larger studies. An international consensus about best prophylaxis to prevent venous thromboembolism in patients with multiple myeloma on treatment is still missing. Therefore, thrombosis in multiple myeloma remains an ongoing issue., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Treatment of multiple myeloma (MM) patients has radically changed over the last years following the introduction of next generation proteasome inhibitors (PI) and immunomodulatory derivative (IMiDs). In the last years, one further therapeutic option for MM patients is represented by monoclonal antibodies (MoAbs), that seem to change the paradigm of MM treatment, particularly for heavily pretreated or double refractory to a PI and IMiDs patients. Antibodies have an immune-based mechanism, induce durable responses with limited toxicity and combine well with existing therapies. The therapeutic effects are prevalently obtained by means of antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), complement-dependent cytotoxicity (CDC) and concurrently by the induction of signals on cell effectors. Immunotherapeutic strategies offer a new and exciting approach to target key molecular pathways that continue to be implicated in the survival of malignant plasma cells. These targets include cell surface proteins (CD38, CD138 [SDC1], B cell maturation antigen [BCMA, TNFRSF17]), cytokines that play a role in plasma cell survival and proliferation (interleukin 6 [IL6] and B cell activating factor), signal regulators of bone metabolism (RANKL [TNFSF11], DKK1) and regulators of the immune system (PD-1[PDCD1], PD-L1[CD274]). This article focuses on new MoAbs and related innovative immunotherapeutic modalities currently under investigation in the treatment landscape of MM.

Multiple myeloma (MM) is a heterogeneous malignancy characterized by the proliferation of abnormal plasma cells in the bone marrow. Multiparametric flow cytometry (MFC) plays a role in the work-up of the disease in view of the aberrant expression of surface antigens. Our study aimed at describing the antigenic profile detected by MFC in a series of newly diagnosed MM patients to correlate the level of expression with other features of the disease. Between April 2018 and June 2022, 84 consecutive MM patients were studied at presentation. CD56 and CD117 were commonly detected, while CD45, CD28, CD20, CD19, CD13 and CD33 were less recurrent. CD20 expression was associated with the type of secretory MM (p=0.041) and with a higher disease burden (p=0.038). CD28 positivity correlated with a lower platelet count at baseline (p=0.005) and with a lower rate of complete response (p=0.038). Furthermore, CD28 positivity and a lower CD138 expression tended to associate with the high-risk chromosomal translocations t(14;16) and t(4;14). The results of this study indicate that in the diagnostic workup of MM, MFC may help to identify different patient subsets and improve risk stratification. These observations need to be validated in larger series of patients with a longer follow-up. [ABSTRACT FROM AUTHOR]