(PA-381) Severe Infections in Newly Diagnosed Multiple Mieloma Patients Treated Frontline with Bortezomib, Lenalidomide and Dexamethasone (VRD) in Four Reference Centers

Introduction:  Monoclonal gammapathies and multiple mieloma (MM) specifically, are associated with immunosupression and an increased risk of infections. Serious infections are a major cause of morbidity and mortality and are particularly frequent during induction therapy. The identification of clinical and biological risk factors associated with infection is essential to develop preventive and supportive strategies. The aim of this study is to describe the incidence and characteristics of infections and associated risk factors in patients initiating frontline treatment with VRD

Methods:   Among 360 patients with newly diagnosed MM and treated with VRD into a prospective clinical trial (EudraCT 2019-0026), 279 (77%) were included in four centers with fully available clinical records for retrospective evaluation. Data collection included baseline characteristics of patients and MM. Data on infectious events included focus, implicated agent, severity and timing of infection as well as an exploratory analysis of associated risk factors.

Results:   Among 279 patients, 156 were male (56%), with a mediana age of 63 years (range 32-88), 63 (23%) were over 70 years-old and 183 (66%) received an autologous stem cell transplantation (SCT) as part of initial therapy. A total of 201 (72%) experienced at least a grade 3–5 infection, 154 (55%) presented 1 or 2, infections per patient ranged up to 8. No significant differences were observed in the infection rate according to immunoglobulin type, renal function, dialysis, or presence of extramedullary disease. A total of 308 grade 3-5 infections were identified, respiratory origin was the most common (n=177), followed by abdominal (n=64), urinary (n=40), and septicèmia of undetermined origin (n=58). Among respiratory infections, 49 were related to Sars-Cov2 (28%), 40 to other viruses (23%) and 30 to encapsulated grampositive bacteria (17%). There were 21 infection-related deaths (7%), mostly within the first three months of induction therapy (13/21), 8 of them with a respiratory origin and 3 due to Sars-Cov2. Patients undergoing ASCT had a higher infection burden (mean 1.9 vs 1.1 infections; p< 0.01), although in these patients infections post-SCT were more frequent than episodis in the first months of therapy. There was 1 episode of death due to pneumonia post-SCT among 183 patients submitted to the procedure while 10/13 of mortal infections occuring during the first three months of treatment were in patients > 70 years (77%).

Conclusions:   This study comprehensively analyzes severe infections in MM patients receiving their first line of therapy. First three months of therapy are those at a higher risk of severe infections including infection-related deaths and argue in favor of individualized prophylactic and proactive therapeutic approaches, particularly in vulnerable subgroups identified by age, treatment intensity, or disease biology.