Low frequency of CD3+CD4+CD161+ T cells correlates with the occurrence of infections in refractory/relapsed multiple myeloma patients receiving lenalidomide plus low-dose dexamethasone treatment

Abstract

The aim of this study was to explore the predictive implications of the composition of immune cell populations prior to lenalidomide plus high-dose dexamethasone (Len-Dex) initiation for the occurrence of infections. We prospectively examined immune cell populations in peripheral blood taken at baseline of lenalidomide plus low-dose dexamethasone (Len-dex) therapy and reviewed clinical and microbiology records in 90 patients with refractory/relapsed multiple myeloma (RRMM). Risk factors for infection were analyzed using logistic regression. During a median of 11 cycles of Len-dex treatment, 52 (57.8%) patients experienced at least 1 infection episode. Of a total of 92 episodes of infection, 58 (63%) episodes were clinically defined, 29 (31.5%) episodes were microbiologically defined, and 5 (5.4%) episodes were fever of unknown origin. Severe episodes were more frequently observed during the first 3 cycles. After adjusting for risk factors for infection based on univariate analyses, multivariate analyses showed that lower Hb (< 10 g/dL) was a clinically independent factor associated with occurrence of infections. Lower frequency (P = 0.044) and absolute count (P = 0.014) of circulating CD3CD4CD161 cells prior to Len-dex treatment were also associated with the occurrence of infection, especially during the first 3 cycles of Len-dex therapy. In addition to several clinical predictive factors, we found that CD3CD4CD161 cells may provide additional information for predicting the occurrence of infection in the early period of Len-dex therapy.

Longitudinal Analysis of Peripheral and Colonic CD161+ CD4+ T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation

“…Th17 cells are believed to play an important antimicrobial role in the tissue, and may be involved in maintaining mucosal integrity [ 37 , 38 , 39 , 40 ]. In immunosuppressed cancer patients or transplantation recipients, a low frequency of CD161 + CD4 + T cells has been associated with increased risk of infections [ 41 , 42 ]. In mice, memory phenotype CD4 T cells producing IFNγ in response to IL-12, a similar characteristic to what we have described in humans for CD161 + CD4 + T cells, provide resistance against Toxoplasma gondii infection in an antigen-independent manner by enhancing adaptive Th1 responses [ 43 ].…”

Case Report: Invasive Fungal Infection and Daratumumab: A Case Series and Review of Literature

“…Moreover, in addition to previously reported risk factors, treatment with Daratumumab reduced both Natural Killer (NK) cells and other CD38-expressing immune cells and cytotoxic T lymphocytes ( 26 – 28 ), providing a biological explanation of a possible increased risk of infection in this population especially for viral infection. Some evidences also reported that NK cells play an important role in the antifungal host response with direct fungal damage and the release of multiple cytokines that activate the immune system ( 29 ).…”

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

“…Regardless, they still represent useful biomarkers to guide management. CyTOF‐based immune phenotyping was restricted to main cellular subsets, but should be expanded in the future to include surface markers informed by both the results of our RNAseq transcriptome analysis as well as recently published data sets 8,13 …”

“…Interestingly, a reduction in circulating CD3 + CD4 + CD161 + cells has recently been associated with severe infection in lenalidomide-and dexamethasone-treated patients. 8 We hypothesised that a more detailed interrogation of immune function in MM patients during treatment would allow for better prediction of infection risk.…”