Infection events in patients with newly diagnosed multiple myeloma with anti-CD38 monoclonal antibody-based first line regimens: A multicentric Italian experience

Multiple myeloma (MM) is a malignancy characterized by the clonal proliferation of plasma cells. It accounts for approximately 1% of all cancers and is the second most common hematologic malignancy after lymphoma. Infections represent a major cause of morbidity and mortality in patients with newly diagnosed multiple myeloma (NDMM), contributing to approximately 45% of early deaths, particularly in elderly individuals and during the initial months of therapy. Current treatment options for MM, including anti-CD38 monoclonal antibodies (CD38 mAbs), proteasome inhibitors, immunomodulatory drugs (such as lenalidomide and thalidomide), and glucocorticoids, have significantly improved clinical outcomes in NDMM patients. However, these therapies are associated with an increased risk of infections. Daratumumab (Dara), an anti-CD38 monoclonal antibody, is a key component of modern MM treatment and is approved for both NDMM and relapsed/refractory MM (RRMM). While Dara has improved patient outcomes, it has also altered the frequency and epidemiology of infections in this population. We conducted a retrospective analysis of 472 NDMM patients treated with Dara-containing regimens at 10 centers of the European Myeloma Network Italy (EMN-I) between 2020 and 2023 to assess the incidence of infectious events (IEs). Among these patients, 148 (31.3%) experienced infectious complications during therapy. No significant differences in infection rates were observed across the three treatment subgroups analyzed. In our experience, the addition of Dara during the induction phase did not increase the frequency, severity, or duration of infections in any of the three cohorts. Although the difference was not statistically significant, we observed an earlier onset of infections in the D-VTD group compared to the others. Further studies are needed to better define the incidence of infections in this patient population and to identify risk factors for infection. This may also inform the role of prophylactic strategies in the clinical management of NDMM.