Immunoparesis

BACKGROUND: Partial immunoparesis, which means at least two suppressed uninvolved immunoglobulins (Igs), had been reported to be associated with poor prognosis in patients with multiple myeloma (MM), but the impact on early infections remains unknown. The purpose of our study was to determine the prognostic implications of partial immunoparesis on early grade ≥3 infections in patients with MM. METHODS: Herein we retrospectively analyzed the clinical data of 123 MM patients between 2012 and 2020 at Nanfang Hospital...

INTRODUCTION/BACKGROUND: Immunoparesis, or low polyclonal immunoglobulin levels, is commonly seen in multiple myeloma (MM), and is associated with poor clinical outcomes. MM can be divided into subgroups with distinct biology and outcomes based on etiologic cytogenetic abnormalities. These include hyperdiploidy and translocations of t(11;14), t(4;14), t(14;16), and t(14;20), with the latter 3 associated with high-risk disease. We hypothesized that the different etiologic cytogenetic abnormalities drive bone marrow microenvironmental changes, resulting in different degrees of immunoparesis, and subgroup-dependent effects on clinical outcomes...

Revaccination after autologous hematopoietic cell transplantation (AHCT) is recommended in post-HCT survivorship guidelines to restore humoral immunity. Data on seroconversion after AHCT and vaccination in multiple myeloma (MM) patients are limited. We investigated the feasibility and effectiveness of vaccination post-AHCT and analyzed the restoration of humoral immunity and patient prognosis. Anti-pathogen titers were measured within a median of 2 days before and 96 days after AHCT and following revaccination in 139 MM patients who had a first AHCT from 2013 to 2016...

INTRODUCTION: Based on risk factors, the Mayo Clinic Multiple Myeloma Group (MCMMG) established a model of progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) at 20 years. It is also described that MGUS with a progressive increase of monoclonal protein (M-protein) and/or immunoparesis (IMP) may be more predisposed to progress to myeloma. Our objective was to make a review of MGUS, to see how those who presented IMP and/or progression of their M-protein, contrasting them with MGUS that presented intermediate/high and high risk according to MCMMG...

Smoldering multiple myeloma (SMM) is an asymptomatic and biologically heterogeneous plasma cell disorder, with a highly variable clinical course. Immunoparesis, defined by total immunoglobulin measurements, has been shown to be an independent risk factor for progression to symptomatic disease. The heavy/light chain (HLC) assay allows precise measurement of the polyclonal immunoglobulin of the same isotype, enabling the evaluation of isotype-matched immunoparesis (IMI). In this study, we prospectively characterized immunoparesis, as determined by HLC measurements, in 53 SMM patients...

Infections are the primary cause of morbidity and mortality in multiple myeloma (MM) patients (pts). The aim of our retrospective analysis was to evaluate incidence and course of COVID-19 infection in a cohort of 351 MM outpatients treated with novel drugs. COVID-19 disease was detected in 50/351 pts (14%); median age was 68 years. Gender, ISS stage, and last treatment lines were as follows: male 32, female 18; ISS-I 19, ISS-II 20, ISS-III 11; daratumumab-based 15, lenalidomide-based 12, bortezomib-based 17, other 6...

Multiple myeloma (MM) is a neoplastic clonal proliferation of plasma cells in the bone marrow microenvironment, characterized by overproduction of heavy- and light-chain monoclonal proteins (M-protein). These proteins are mainly found in the serum and/or urine. Reduction in normal gammaglobulins (immunoparesis) leads to an increased risk of infection. The primary site of origin is the bone marrow for nearly all patients affected by MM with disseminated marrow involvement in most cases. MM is known to involve bones and result in myeloma bone disease...

We analyzed 171 patients with asymptomatic IgM monoclonal gammopathies (64 with IgM monoclonal gammopathy of undetermined significance-MGUS and 107 with smoldering Waldenström macroglobulinemia - SWM) who had a bone marrow (BM) evaluation performed at diagnosis. Abnormal free-light chain ratio (53% vs. 31%) and MYD88 mutation prevalence (66% vs. 30%) were higher in patients with SWM. No other differences were found among groups. With a median follow-up of 4.3 years, 14 patients progressed to Waldenström macroglobulinemia, 1 to amyloidosis, and 28 died without progression...

BACKGROUND AND AIMS: Immunoregulatory checkpoint receptors (CR) contribute to the profound immunoparesis observed in alcohol-related liver disease (ALD) and in vitro neutralization of inhibitory-CRs TIM3/PD1 on anti-bacterial T-cells can rescue innate and adaptive anti-bacterial immunity. Recently described soluble-CR forms can modulate immunity in inflammatory conditions, but the contributions of soluble-TIM3 and soluble-PD1 and other soluble-CRs to immune derangements in ALD remain unclear...

Despite the outstanding progresses in Multiple Myeloma treatment options in the last decades, it remains an incurable disease nowadays. Infectious events are a complication due to an impaired immune system associated with MM, sometimes a life-threatening one, particularly on the first months after the diagnosis. Both the underlying disease and treatment can contribute to the infection risk, so a biomarker that assess this risk could be highly relevant for a more tailored management of the patient. The measurement of the heavy+light chain (HLC) pairs of immunoglobulins in serum allows the quantification of both the monoclonal component and the non-monoclonal immunoglobulin of the same isotype...

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We retrospectively analyzed immunosuppression status in 287 newly diagnosed multiple myeloma (MM) patients and assessed the prognostic value of immunoparesis on survival. Deep immunoparesis was defined that one of uninvolved immunoglobulins was below 50% the lower limit of normal ranges, partial immunoparesis was defined at least two suppressed uninvolved immunoglobulins. We found that patients with deep and partial immunoparesis had a significantly shorter median overall survival (OS) and progression-free survival (PFS)...

INTRODUCTION: Little is known on continued response following completion of therapy in light chain (AL) amyloidosis. METHODS: We studied 373 AL amyloidosis patients who achieved complete response (CR) or very good partial response (VGPR) to first-line therapy. RESULTS: By end of therapy (EOT), 46% of patients achieved a CR and 54% a VGPR. With no further therapy, 17.5% of patients were upstaged from VGPR to CR (delayed CR), with a median of 9 months...

Despite significant progress made in the treatment of patients with multiple myeloma (MM) in the last decade, for patients with early relapse or rapidly progressing high-risk disease, allogeneic hematopoietic stem cell transplantation (SCT) might be an option leading to long-term survival. Here, we retrospectively analyzed the outcomes of 90 MM patients who received allogeneic SCT in our center between 1999 and 2017. We specifically assessed the association of impaired humoral immune reconstitution, referred to as immunoparesis, and post-transplant survival...

Smouldering multiple myeloma (SMM) presents without MM defining symptoms. We aimed to identify patients with SMM with an 80% risk of progression within 2 years using only serum parameters. In total, 527 patients with SMM were included and divided into a training group (287 patients from the Czech Myeloma Group [CMG]) and an independent validation group (240 patients from Heidelberg). The median follow-up was 2·4 and 2·5 years, respectively. Progression to MM occurred in 51·9% of the CMG and 38·8% of the Heidelberg patients, respectively...

Characterisation and prognostic impact of immunoparesis in relapsed multiple myeloma (MM) is lacking in the current literature. We evaluated 258 patients with relapsed MM, diagnosed from 2008 to 2015, to investigate the prognostic impact of deep immunoparesis on post-relapse survival. On qualitative immunoparesis assessment, no, partial and full immunoparesis was present in 9%, 30% and 61% of patients, respectively. Quantitative immunoparesis was assessed by computing the average relative difference (ARD) between polyclonal immunoglobulin(s) and corresponding lower normal limit(s), with greater negative values indicating deeper immunoparesis...

We investigated incidence, characteristics and outcome of patients with macrofocal multiple myeloma (MFMM) treated mainly with novel therapies. Based on definition (BMPCs <20% and lytic lesions/plasmacytomas, without anemia, renal insufficiency or hypercalcemia) we identified 140 patients with MFMM, among 4650 myeloma patients (3%). Twice the number of patients with typical myeloma were used as controls; 60% were <65 years and 70% had advanced bone disease. Plasmacytomas were more frequent in MFMM compared with standard myeloma (68% vs 15%, P < ...

The characteristics of the IgA plasma cell neoplasms are not clearly reported in the literature. The main goal of this study is to examine IgA plasma cell neoplasms (PCN) and to compare them to IgG lesions. After at least 5 years from the identification of an M protein, 98 cases were selected, the presentation and clinical evolution of 45 IgA neoplasms were compared to 43 cases of IgG gammopathies. The classification at presentation as monoclonal gammopathy of undermined significance (MGUS)-22 of 45 IgA and 20 of 43 IgG (49 vs 46%), plasma cell myeloma (PCM)-22 of 45 IgA and 22 of 43 IgG (49 vs 51%) and smoldering PCM (SPCM)-1 each (2% for both) was essentially identical...

The dynamics of immunoaging and the onset of immunoparesis in healthy individuals and cancer patients has been controversially discussed. Moreover, the role of chemotherapy on T cell regeneration needs further elucidation in light of novel immunotherapies that have become standard of care for many elderly cancer patients. We used next-generation immunosequencing to study T cell receptor (TCR) repertoire metrics on 346 blood samples from healthy individuals and cancer patients producing a dataset with around 8...

Importance: Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Risk models that estimate the risk of progression from MGUS to multiple myeloma use data from a single time point, usually the initial workup. Objective: To longitudinally investigate the alterations of serum immune markers with stable vs progressive MGUS. Design, Setting, and Participants: This prospective cross-sectional cohort study included 77 469 adult participants aged 55 to 74 years in the screening arm of the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnosis of progressing MGUS (n = 187) or stable MGUS (n = 498), including light-chain subtype, from November 1993, through December 2011...