Abstract

New treatments options introduced during recent decades have improved the survival of multiple myeloma(MM)patients.Managing the complications of the disease and its treatment, such as infections become more important as MM-patients survive longer. Infections are a significant cause of morbidity and a leading cause of death in MM-patients.Effect of novel therapies on the risk of infection remains to be established and new trials on prophylactic measures are needed.These advances have transformed myeloma into a chronic condition, with multiple relapses resulting in cumulative immunosuppression and higher risk of infection. In addition to the immunodeficiency related to myeloma, the type of anti-myeloma therapy used also plays a role in the development of infectious events.We aimed to study the development of severe infectious events of grade 3-4 requiring often hospitalization in a group of patients under treatment at diagnosis as well as at relapse. We evaluated the impact of the type of anti-myeloma therapy and of the disease features on patients' infectious complications in the context of novel agents.We retrospectively reviewed data from 195 myeloma patients diagnosed from 1999 to 2016 in order to assess type and outcome of infections (Table 1). 7 of these were life-threatening (3 viral interstitial pneumonias and 4 gram negative sepsis)and 103 have resulted in discontinuation of therapy(respectively 73 bacterial, 10 fungal,18 viral and 2 parasitic-infectious-complications). We focus on time of occurrence and number of prior therapeutic lines and on disease biological aggressiveness.Our aim was to define risk-factors and to organize an effective antimicrobial prophylaxis strategy in our cohort of patients.In our analysis 30 patients presented a FUO(fever of unknown origin)without isolation of pathogens.They were 19 elderly-patients and 11 young in a neutropenic phase after chemotherapy. They showed defervescence following antibiotic therapy with piperacillin-tazobactam.165 patients presented infectious complications with a well-known etiology (Figure 1): 100 bacterial, 45 viral, 15 fungal and 5 parasitic infections. Pathogens isolated were:Candida-Albicans followed by C.Parapsylosis and Aspergillus-Flavus among fungal infections,E.Coli,Klebsiella-Pneumoniae and Pseudomonas-aeruginosa between bacterial complications,CMV,HSV,HZV in viral manifestations and Leishmanias among parasitic-events.Advanced age is a meaningful risk-factor togheter with biologically aggressiveness and relapse condition. The majority of patients were older than 65 years (125 as 76%) in a relapse setting (125 as 77%).Kind of anti-myeloma therapy used also plays a role in the development of infection. Specifically the predominant part of patients developing fungal infections(13 as 89%)showed neutropenia after chemotherapy or previous therapy with Imids. The majority of patients with viral infections(39 as 87%) presented lymphopenia and previous therapies bortezomib-based.Bacterial infections have shown mostly prevalent in neutropenic-phases (88 as 88%) usually in relapse phases (78 as 78%)or in hypogammaglobulinemic patients(68 as 68%).Finally most of parasitic infections have been shown after high doses steroid treatment and with more than 2 of therapeutic lines(100%).Severe infections represent a significant comorbidity in MM, often underestimated, in all phases of the disease expecially in refractory/relapsed patients.Immunoglobulin-replacement-therapy or antibiotic-prophylaxis may possible have a protective-role in high risk old patients with high ISS stage and aggressive disease. Variety of factors underlies susceptibility to infections including defects of innate and adaptive-immunity(neutropenia,hypogammaglobulinemia).Need for antimicrobial-prophylaxis depends on risk for and seriousness of infections.Based on our experience,in the first three-months of therapy with IMIDs we now begin prophylactic antibacterial and antifungal therapy (quinolone and fluconazole).All patients treated to date(30 in total)did not require therapy-discontinuation.High-risk-patients should receive antimicrobial-prophylaxis and trials on prophylactic-measures are needed.Key to the management of infection is the understanding of the specific risk factors and periods in order to perform a risk adjusted prophylactic and treatment strategies.

Disclosures

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.