Predicting Risk of Infection in Patients with Newly Diagnosed Multiple Myeloma: Utility of Immune Profiling

Abstract

BackgroundA translational study in patients with myeloma to determine the utility of immune profiling to predict infection risk in patients with hematological malignancy was conducted.MethodsBaseline, end of induction, and maintenance peripheral blood mononuclear cells from 40 patients were evaluated. Immune cell populations and cytokines released from 1 × 106 cells/ml cultured in the presence of a panel of stimuli (cytomegalovirus, influenza, S. pneumoniae, phorbol myristate acetate/ionomycin) and in media alone were quantified. Patient characteristics and infective episodes were captured from clinical records. Immunological variables associated with increased risk for infection in the 3-month period following sample collection were identified using univariate analysis (p < 0.05) and refined with multivariable analysis to define a predictive immune profile.Results525 stimulant samples with 19,950 stimulant–cytokine combinations across three periods were studied, including 61 episodes of infection. Mitogen-stimulated release of IL3 and IL5 were significantly associated with increased risk for subsequent infection during maintenance therapy. A lower Th1/Th2 ratio and higher cytokine response ratios for IL5 and IL13 during maintenance therapy were also significantly associated with increased risk for infection. On multivariable analysis, only IL5 in response to mitogen stimulation was predictive of infection. The lack of cytokine response and numerical value of immune cells were not predictive of infection.ConclusionProfiling cytokine release in response to mitogen stimulation can assist with predicting subsequent onset of infection in patients with hematological malignancy during maintenance therapy.

Successful identification of predictive profiles for infection utilising systems‐level immune analysis: a pilot study in patients with relapsed and refractory multiple myeloma

“…In concordance with previous studies, 4 the main immune cell populations and their effector/memory status (CD4 + , CD8 + , NK, DC, B cells and monocytes) did not differ between patients who did or did not subsequently development infection. This highlights that overall immune cell numbers per se did not predict infection risk.…”

“…This is especially true for patients with relapsed and refractory disease managed with multiple lines of therapy 2,3 . In a previous study, Th2 cytokine signatures, particularly IL‐3 and IL‐5 release from PBMCs in response to PMA stimulation, were associated with risk of infection within 3 months 4 . Measurement of the immune response to a pan‐antigen (mitogen) such as PMA could be useful in predicting future risk of infection.…”

“…In a previous exploratory study of immune variables associated with increased risk of infection in patients with newly diagnosed MM, a Th2‐dominant cytokine response, detected after in vitro mitogen stimulation, was associated with an increased risk of infection. In particular, the IL‐5 response to PMA antigen stimulation was a key predictor of infection risk 4 . Other groups have utilised mass cytometry and detection of transcriptomes individually as a means of predicting infection outcomes in patients undergoing HSCT 5,6 .…”

A predictive model for risk of early grade ≥ 3 infection in patients with multiple myeloma not eligible for transplant: analysis of the FIRST trial

“…A pathogen could not be specified in a substantial proportion of infections reported limiting further elucidation on the types of interventions that may be useful in this setting. Although it is common in MM trials and in practice that a substantial proportion of infections have no pathogen specified [ 21 , 22 ], additional MM studies with data on infections with specified causes are needed to determine possible patterns of specific types of infections and appropriate preventative therapies for patients at risk. Our model also requires further prospective interrogation for additional validation, particularly in proteasome inhibitor-based studies.…”

Infectious Complications in Multiple Myeloma Patients Receiving Various Antitumor Regimens

“…Следует отметить, что противоопухолевые препараты, наряду с цитостатическим эффектом, оказывают иммуносупрессивное воздействие, могут усугублять иммунодефицит и индуцировать развитие инфекционных осложнений, причем вызванных в части случаев определенными возбудителями. У больных ММ наблюдаются нарушения клеточного и гуморального звеньев иммунитета, происходит подавление факторов неспеци фической защиты [7,8]. Комплексные нарушения иммунного статуса, включающие снижение синтеза поликлональных иммуноглобулинов, числа лимфоцитов CD4+, иммунорегуляторного индекса (CD4/ CD8), угнетение фагоцитарной функции нейтрофилов, нарушение продукции цитокинов, могут предрасполагать к развитию инфекционных осложнений различной этиологии, как бактериальной, так и вирусной, грибковой.…”