Assessment of minimal residual disease (MRD) is becoming a standard diagnostic tool for curable hematological malignancies such as chronic and acute myeloid leukemia. Multiple myeloma (MM) remains an incurable disease, as a major portion of patients even in complete response eventually relapse, suggesting that residual disease remains. Over the past decade, the treatment landscape of MM has radically changed with the introduction of new effective drugs and the availability of immunotherapy, including targeted antibodies and adoptive cell therapy. Therefore, conventional serological and morphological techniques have become suboptimal for the evaluation of depth of response. Recently, the International Myeloma Working Group (IMWG) introduced the definition of MRD negativity as the absence of clonal Plasma cells (PC) with a minimum sensitivity of <10−5 either by next-generation sequencing (NGS) using the LymphoSIGHT platform (Sequenta/Adaptative) or by next-generation flow cytometry (NGF) using EuroFlow approaches as the reference methods. While the definition of the LymphoSIGHT platform (Sequenta/Adaptive) as the standard method derives from its large use and validation in clinical studies on the prognostic value of NGS-based MRD, other commercially available options exist. Recently, the LymphoTrack assay has been evaluated in MM, demonstrating a sensitivity level of 10−5, hence qualifying as an alternative effective tool for MRD monitoring in MM. Here, we will review state-of-the-art methods for MRD assessment by NGS. We will summarize how MRD testing supports clinical trials as a useful tool in dynamic risk-adapted therapy. Finally, we will also discuss future promise and challenges of NGS-based MRD determination for clinical decision-making. In addition, we will present our real-life single-center experience with the commercially available NGS strategy LymphoTrack-MiSeq. Even with the limitation of a limited number of patients, our results confirm the LymphoTrack-MiSeq platform as a cost-effective, readily available, and standardized workflow with a sensitivity of 10−5. Our real-life data also confirm that achieving MRD negativity is an important prognostic factor in MM.

Life expectancy of multiple myeloma (MM) patients has improved in last years due to the advent of anti-CD38 monoclonal antibodies in combination with immunomodulators and proteasome inhibitors. However, morbidity and mortality related to infections remain high and represent a major concern. This paper describes the “real life” risk of invasive fungal infections (IFI) in patients treated with daratumumab-based therapy and reviews the relevant literature. In a series of 75 patients we only observed three cases of fungal pneumonia. Unfortunately, the early signs and symptoms were not specific for fungal infection. Diagnostic imaging, microbiology and patient history, especially previous therapies, are critical in the decision to start antifungal treatment. Recognising the subgroup of MM patients with high risk of IFI can increase the rate of diagnosis, adequate treatment and MM-treatment recovery.

Respiratory syncytial virus (RSV) is one of the most common respiratory viruses that can affects not only infants but also elderly and immunocompromised patients (pts). After the emergence of SARS-CoV-2, a reduction of RSV spread was documented probably due to the implementation of public health measures and social distancing. Reports from European Center for Disease Prevention and Control (ECDC) highlight the intensified circulation of RSV in many European countries, with an increased transmission rate in all population groups and an earlier start to the RSV 2022-23 season. The impact of RSV infection is assessed as very low in general population contrary to what happens in high-risk groups such as immunocompromised pts.

Quadruplet induction with Daratumumab, Bortezomib, Thalidomide and Dexamethasone (Dara-VTd) has become the standard treatment for transplant-eligible newly diagnosed multiple myeloma patients (NDMM). Despite improved response rates compared to VTd, concerns with stem-cell mobilization and collection emerged in CASSIOPEIA trial. Indeed, after a mobilization approach based on cyclophosphamide (2 to 3 g/m 2 ) and granulocyte colony-stimulating factor (G-CSF) 10 μg/kg/day, patients treated with Dara-VTd experienced a greater use of plerixafor as well as a lower median number of collected CD34 + cells/Kg.