Immune Paresis in Treated Multiple Myeloma Involving Adaptive As Well As Innate Immunity: Monocentric Experience of 120 Patients with Serious Infectious Complications Retrospectively Analyzed

Survival of multiple-myeloma(MM)patients has improved in the last decade,with persistence of immunological-impairment that deteriorates their life-expectancy.Herein we described the occurrence of severe-infectious-events of grade 3-4 in a cohort of 120 MM-patients diagnosed from 1999-to-2015 in order to assess type and outcome of infections.Five of these were life-threatening(3viral interstitial-pneumonia and 2gram-negative-sepsis),three have required intervention of intensive-care(1 viral and 1fungal-pneumonia and 1 gram-positive-sepsis) and 68 have resulted in discontinuation of therapy(respectively 34 bacterial, 29 fungal,3 viral and 2parasitic-infectious-complications).We focused on time of development and number of prior therapeutic-lines and on disease-biological-aggressiveness.Our aim was to define risk-factors and correct-antimicrobial-prophylaxis.Anti-infective prophylaxis used was acyclovir with bortezomib.In our study 10-patients presented a FUO without isolation of pathogens.They were 7-elderly-patients and 3 young in neutropenic-phases.They presented defervescence following antibiotic-therapy with piperacillin-tazobactam.110 patients showed complications with an etiology (70 bacterial, 20 viral,15 fungal and 5parasitic-infections).Pathogens encountered often were:Candida-albicans followed by Candida-parapsylosis and Aspergillus-flavus inside of fungal-infections, E.coli,Klebsiella-Pneumoniae, Streptococcus-mitis between bacterial-complications,CMV,Herpes-Zoster in viral-manifestations and Leishmania among parasitic-events.Advanced-age is a powerful risk-factor togheter with biologically-aggressiveness and relapse-condition.The majority of patients were older than 65-years(68%)in a relapse-setting (70%).Only 19% were fit according to frailty-score,39% frail and the predominant part(42%) unfit.Specifically, the majority of patients developing fungal-infections(86%)presented neutropenia due to chemotherapy and to previous-therapy with ImiDs. Most of patients with viral-infections(65%)showed lymphopenia and previous therapies-bortezomib-based.Bacterial-infections have shown mostly prevalent in neutropenic-phases usually in relapse-phases (62%)or in hypogammaglobulinemic patients(72%). Finally,most of parasitic-infections have been shown after high-doses-steroid-treatment and with more than 2 therapeutic-lines(100%). Variety of factors underlies susceptibility to infections including defect 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(20 in total)did not require therapy-discontinuation.High-risk-patients should receive antimicrobial prophylaxis and trials on prophylactic-measures are needed.