Severe and continuous immunoparesis during induction or maintenance therapy in nontransplant patients with multiple myeloma is a sign of poor prognosis.

OBJECTIVE: Multiple myeloma (MM) varies in clinical behavior, response to treatment and prognosis due to the heterogeneity of the disease. Data on the association between the immunoparesis status during treatment and prognosis in nontransplant MM patients are limited. METHODS: In a retrospective analysis of 142 patients with MM, we examined the relationship between immunoparesis status and prognosis during treatment. All patients received novel agent-based therapy and did not undergo autologous stem cell transplantation. One, two, or three uninvolved immunoglobulins (Igs) below the lowest thresholds of normalcy were used to identify immunoparesis. RESULTS: Patients with a greater degree of immunoparesis during treatment had shorter progression-free survival (PFS) and overall survival (OS). A total of 46.5% of the patients had severe and continuous immunoparesis (at least two uninvolved Igs suppressed continuously during treatment), representing a worse prognosis than those with complete or partial normalization of Igs during treatment. Among patients who achieved at least complete remission, PFS was poor in patients with severe and continuous immunoparesis. Furthermore, severe and continuous immunoparesis during treatment was a poor prognostic factor for PFS and OS according to multivariate analyses. CONCLUSION: The degree of immunoparesis during treatment is a follow-up indicator for survival in nontransplant myeloma patients, and severe and continuous immunoparesis in nontransplant myeloma patients might be a sign of poor prognosis.

Development of a nomogram prognostic model for early Grade ≥ 3 infection in newly diagnosed multiple myeloma based on immunoparesis.

BACKGROUND: Infection, a significant cause of death in multiple myeloma (MM) patients, is a common complication and is closely associated with immunoparesis. There exists no clear definition of early infection, so early infection is defined in this paper as the occurrence within 3 months after diagnosis, considering the high incidence of infections within 3 months after diagnosis. This study established a new nomogram model based on immunoparesis to identify MM patients with high-risk early infection. METHODS: A retrospective collection of 430 NDMM patients from June 2013 to June 2022 was conducted, and the patients were further divided into a training cohort and a validation cohort. In the training cohort, the least absolute shrinkage and selection operator (LASSO) was used to select the best variables that can be used to establish a new nomogram prediction model. Validation was performed in the validation and entire cohorts. RESULTS: After diagnosis, 67.7 % of the patients suffered from severe infection within 1 year, and 59.5 % experienced the first severe infection within 3 months. Variables associated with an increased risk of severe infection in the first 3 months included: BMPC, D-dimer, serum ß2 microglobulin, immunoparesis, albumin, and eGFR. The nomogram based on the above six factors achieved a good C-index of 0.754, 0.73, and 0.731 in predicting early infection in the training cohort, validation cohort, and entire cohort, respectively. Finally, the time-dependent receiver operating characteristic (ROC) curve and decision curve analysis (DCA) of the nomogram showed that the model provided superior diagnostic capacity and clinical net benefit. CONCLUSION: In this study, we established a nomogram model to predict early grade ≥ 3 infection in NDMM patients. This model can assist clinicians in identifying NDMM patients with high-risk infections and improve their prognosis through early intervention.

Polyclonal immunoglobulin recovery in patients with newly diagnosed myeloma receiving maintenance therapy after autologous haematopoietic stem cell transplantation with either carfilzomib, lenalidomide and dexamethasone or lenalidomide alone: Subanalysis of the randomized phase 3 ATLAS trial.

Previous studies suggest that postautologous stem cell transplant (ASCT) recovery of polyclonal immunoglobulin from immunoparesis in patients with multiple myeloma is a positive prognostic marker. We performed a longitudinal analysis of polyclonal immunoglobulin concentrations and unique B-cell sequences in patients enrolled in the phase 3 ATLAS trial that randomized 180 subjects to either carfilzomib, lenalidomide, dexamethasone (KRd) or lenalidomide (R) maintenance. In the KRd arm, standard-risk patients with minimal residual disease negativity after six cycles de-escalated to R alone after cycle 8. One year from the initiation of maintenance at least partial recovery of polyclonal immunoglobulin was observed in more patients on the R arm (58/66, p < 0.001) and in those who de-escalated from KRd to R (27/38, p < 0.001) compared to the KRd arm (9/36). In patients who switched from KRd to R, the concentrations of uninvolved immunoglobulin and the number of B-cell unique sequences increased over time, approaching values observed in the R arm. There were no differences in progression-free survival between the patients with at least partial immunoglobulin recovery and the remaining population. Our analysis indicates that patients receiving continuous therapy after ASCT experience prolonged immunoparesis, limiting prognostic significance of polyclonal immunoglobulin recovery in this setting.

Clinical Considerations for Immunoparesis in Multiple Myeloma.

Multiple myeloma is a relatively common clonal plasma cell disorder, comprising 17% of hematologic malignancies. One of the hallmark features of this disease is immunoparesis, which is characterized by the suppression of immunoglobulin polyclonality. Though not entirely elucidated, the mechanism behind this process can be attributed to the changes in the tumor microenvironment. All treating clinicians must consider potential complications related to immunoparesis in the management of multiple myeloma. Though not explicitly described in large data series, the increased risk of infection in multiple myeloma is likely, at least in part, due to immunoglobulin suppression. Additionally, the presence of immunoparesis serves as a prognostic factor, conveying poorer survival and a higher risk of relapse. Even in the era of novel agents, these findings are preserved, and immunoglobulin recovery also serves as a sign of improved outcome following autologous HSCT. Though not within the diagnostic criteria for multiple myeloma, the presence and degree of immunoparesis should be at diagnosis for prognostication, and immunoglobulin recovery should be tracked following myeloablative therapy and autologous HSCT.

Serological Response to Vaccination after Autologous Transplantation for Multiple Myeloma Is Associated with Improved Progression-Free and Overall Survival.

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. Most (84%) patients received at least one dose of any planned vaccines. High-dose melphalan with AHCT restored measurable immunity in 18% of patients. In an additional >60% of patients, seroconversion occurred after vaccination; however, despite vaccination, 20% of patients remained seronegative for most pathogens. Attainment of MM complete response post-AHCT was associated with higher rates of seroconversion which yielded significantly longer progression-free and overall survival. Our study demonstrates the feasibility of post-AHCT vaccination, supporting measurement of post-vaccination titers to determine which patients should be considered for antimicrobial prophylaxis, as seroconversion does not occur in all patients. Titer seroconversion is a potential indicator of the immunological effects of AHCT, with restoration of humoral immunity demonstrating improved survival.

[Monoclonal gammopathy of undetermined significance and evolution to myeloma: Experience in 153 patients]. / Gammapatía monoclonal de significado incierto y evolución a mieloma múltiple: Experiencia en 153 pacientes.

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. METHODOLOGY AND MATERIALS: A review of the MGUS objectified during the realization of a serum proteinogram (SPEP) was carried out during 2010-2014, in our area. Serum immunoglobulins, serum immunofixation (IFs), and serum free light chain ratio (FLCr) were determined for all MGUS. RESULTS: Of the 153 MGUS that are followed up for 4 years, 6 progress to MM. Of these 6 MM, 5 progress from MGUS with intermediate/high risk taking into account the MCMMG. Of these 5, 3 have IMP or progression of their M-protein. 2 present IMP plus progression of their M-protein. The sixth MM evolves from a MGUS without any risk factor, but with progression of its M-protein plus IMP. CONCLUSIONS: IMP and/or M-protein progression are important risk factors to be taken into account in the MGUS, in the first years after diagnosis, due to their possible evolution to MM.

Immunoparesis defined by heavy/light chain pair suppression in smoldering multiple myeloma shows initial isotype specificity and involves other isotypes in advanced disease.

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. Severe IMI was present in 51% of patients, while severe IP of uninvolved isotypes (HLC IP) was present in 39%. Most of the patients with severe HLC IP presented with severe IMI, but not the other way around. Isotype specificity of immune suppression was suggested by lower relative values of isotype-matched HLC pairs, both for IgG and IgA SMM. Severe IMI was associated with other risk factors for progression while patients with severe IMI and severe HLC IP showed an even higher risk profile. Both severe IMI and severe IgM HLC IP showed a significantly shorter time to progression. Finally, gene expression analysis demonstrated differences in the bone marrow microenvironment between patients with IMI and IMI plus HLC IP, with an increased expression of genes associated with cytolytic cells. In conclusion, our data supports isotype specificity of early immunoglobulin suppression mechanisms. While suppression of both involved and uninvolved isotypes is associated with risk of progression, the later appears to develop with more advanced disease and could be mediated by different mechanisms.

Defining an Ultra-Low Risk Group in Asymptomatic IgM Monoclonal Gammopathy.

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. The MYD88 mutation was found in 53% of patients (available in 160 patients). Multivariate analysis showed that immunoparesis (subhazard ratio-SHR 10.2, 95% confidence interval-CI: 4.2-24.8; p < 0.001) and BM lymphoplasmacytic infiltration ≥ 20% (SHR: 6, 95% CI: 1.6-22.1; p = 0.007) were associated with higher risk of progression. We developed a risk model based on these two risk factors. In the absence of both variables, an ultra-low risk group was identified (SHR 0.1, 95% CI 0.02-0.5; p = 0.004), with 3% and 6% of cumulative incidence of progression at 10 and 20 years, respectively. Bootstrap analysis confirmed the reproducibility of these results. This study finds immunoparesis and BM infiltration as biomarkers of progression as well as a low-risk group of progression in asymptomatic IgM monoclonal gammopathies.

HLC Pair Suppression as a Risk Factor for Bacterial Bloodstream Infections and Early Mortality in Newly Diagnosed Intact Immunoglobulin Multiple Myeloma Patients.

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. This approach has demonstrated high sensitivity for the detection of the clonality and prognostic value for MM. HLC pair suppression itself has prognostic power and it has been proposed to be a reflection of the immune system' attempt to control the tumor. In this study we evaluated the impact of the HLC pair suppression on the rate of bloodstream infections (BSI) and early death in 115 newly diagnosed MM patients. Twenty-one percent of the patients suffered a BSI in the first 6 months after diagnosis, of which 58% died within this period, accounting to 67% of the early deaths in global and highlighting the major impact of infections on MM patients in a "real world" setting. Severe HLC pair suppression identified patients with a higher risk of early BSI (HR: 6,97, p=0,009), and extreme HLC pair suppression together with BSI event and age >65 were independent risk factors for early death (p<0,001). Based on these factors, a stratification model was generated to allow identify patients at a higher risk of early death and poorer OS, with an apparently better performance than the ISS on the early death context. In conclusion, HLC pair suppression associates with both a higher risk of life-threatening early infection and early death in newly diagnosed MM patients. Patients older than 65 with extreme HLC pair suppression and BSI are at a high risk of early death, and thus patients presenting with these criteria have a very adverse prognosis.

Partial immunoparesis contributes to risk of early infections in patients with multiple myeloma.

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. All patients received bortezomib-based regimens. The relationship between early grade ≥3 infections and partial immunoparesis was investigated using Cox regression analysis. RESULTS: Our data showed partial immunoapresis was found in 63% MM patients. Partial immunoparesis was significantly related to elevated beta-2-microglobulin (B2M), decreased estimated glomerular filtration rate (eGFR) and progressive international staging system (ISS) stage (P<0.05). Especially, univariate Cox regression analysis showed partial immunoparesis was significantly correlated with early grade ≥3 infections (P=0.003). Moreover, multivariate Cox regression analysis showed partial immunoparesis was an independent significant prognostic factor for early grade ≥3 infections [odds ratio (OR) =3.048; 95% confidence interval (CI): 1.429-6.504; P=0.004]. Furthermore, partial immunoapresis could improve the infection risk model built by Dumontet et al. CONCLUSIONS: Our study showed that partial immunoparesis could predict early infections in patients with MM, which may be used to identify the high risk patients for infections and guide strategies for infection prevention.

Deep and partial immunoparesis is a poor prognostic factor for newly diagnosed multiple myeloma patients.

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). Moreover, deep and partial immunoparesis was a poor prognostic factor for OS and PFS in univariate and multivariable analyses. To reduce the bias between the groups, we performed a 1:1 propensity score matching technique for analysis and found that patients with deep and partial immunoparesis also had shorter OS and PFS. Our study showed that deep and partial immunoparesis can be defined an independent poor prognostic factor for patients with newly diagnosed MM.

Characterization and prognostic implication of delayed complete response in AL amyloidosis.

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. Compared with CR and VGPR at EOT, patients with a delayed CR were characterized by higher proportion of t(11;14) and lower rate of trisomies. Autologous stem cell transplant was more frequent in the delayed CR group. Patients with a delayed CR were characterized by minimal residual disease negativity and organ response rates similar to patients with CR at EOT and higher than patients achieving VGPR at EOT. Patients with a delayed CR had a longer PFS/OS compared to patients with CR or VGPR by EOT (median PFS 149 vs 92 vs 52 months, P < .001; 10-year OS 87% vs 71% vs 56%, P < .001). CONCLUSIONS: This study characterizes delayed CR in AL amyloidosis, highlights its prognostic impact which is at least similar to those who achieved CR at EOT, and underlines another aspect of response monitoring.

Long-term survival and polyclonal immunoglobulin reconstitution after allogeneic stem cell transplantation in multiple myeloma.

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. Sixty-four patients received allogeneic SCT in relapse following 2-7 lines of therapy; 26 patients received upfront tandem autologous-allogeneic SCT. With a median follow-up of 76 months, OS and PFS were 52.6% (95% CI 42.9-64.3) and 36.4% (95% CI 27.6-47.9) at 2 years and 38.6% (95% CI 29.2-51.1) and 25.3% (95% CI 17.5-36.4) at 5 years, respectively. Receiving more than two therapy lines prior to transplantation was an independent risk factor for OS (HR 3.68, 95% CI 2.02-6.70) and PFS (HR 3.69, 95% CI 2.09-6.50). In a landmark analysis at day 200, prolonged immunoparesis was associated with reduced OS (HR 3.22, 95% CI 1.14-9.11). Allogeneic stem cell transplantation offers an additional treatment element that may lead to long-term remission in selected patients with poor prognosis, probably exploiting graft-versus-myeloma effects. Immunoparesis could potentially serve as an indicator for impaired survival following allogeneic transplantation, an observation to be further studied prospectively.

A new risk model to predict time to first treatment in chronic lymphocytic leukemia based on heavy chain immunoparesis and summated free light chain.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is frequently accompanied by immune dysregulation. AIMS: In this multicenter prospective study, we investigated whether heavy + light chains (HLC: IgGκ, IgGλ, IgAκ, IgAκ, IgMκ, IgMλ) and IgG subclasses (IgG1, IgG2, IgG3, and IgG4) could be used as novel prognostic markers of immunoparesis in 105 treatment-naïve patients with CLL. RESULTS: Heavy + light chains immunoparesis of ≥1, ≥2, and ≥3 isotypes was evident in 74 (70%), 58 (55%), and 36 (34%) patients, respectively. Severe HLC immunoparesis was identified in 40 (38%) patients. Of the IgG subclasses, IgG1 and IgG2 were most frequently suppressed, affecting 46 (44%) and 36 (34%) patients, respectively; 63 (60%) patients had low levels of at least one IgG subclass. In multivariate analysis, severe HLC immunoparesis (hazard ratio [HR]: 36.5; P = .010) and ΣFLC ≥ 70 mg/L (HR: 13.2; P = .004) were the only factors independently associated with time to first treatment (TTFT). A risk model including these variables identified patients with 0, 1, and 2 risk factors and significantly different TTFT (P < .001). Patients with two factors represented an ultra-high-risk group with a median TTFT of only 1.3 months. CONCLUSION: The above findings demonstrate the potential for the use of HLC immunoparesis, together with sFLC measurements, as future prognostic biomarkers in CLL.

Immunoparesis recovery 1 year after ASCT is independently associated with favorable survival in patients with symptomatic multiple myeloma who undergo autologous stem cell transplantation.

Immunoparesis is defined as a reduction in the levels of one, two, or three uninvolved immunoglobulins. However, there are very limited data on the incidence and prognostic significance of immunoparesis recovery 1 year after autologous stem cell transplantation (ASCT) in MM. We reviewed medical records of de novo MM patients who received ASCT at Beijing Chao Yang hospital. One hundred eight MM patients were included in the study. Conventional chemotherapy was administered as induction regimen in 16 patients (14.8%), whereas novel agents were used in 92 patients (85.2%). Most patients had immunoparesis at diagnosis (89.1%) and at the moment of ASCT as well (75%). After a median follow-up of 49 months, in the group with immunoglobulin recovery 1 year after ASCT, there was a trend towards longer progression-free survival (PFS) than in the group with immunoparesis (P = 0.054). And overall survival (OS) was significantly longer in patients with immunoparesis recovery (P = 0.004). In multivariate analysis, immunoparesis recovery 1 year after ASCT was independently associated with improved OS (P = 0.016). In conclusion, lack of immunoparesis recovery 1 year after ASCT in MM patients is associated with significantly shorter OS and this group of patients needs new treatment strategy to improve the prognosis.

Immunoparesis in symptomatic multiple myeloma at diagnosis affects PFS with bortezomib-containing induction therapy, but not ASCT consolidation.

In novel agent era, the impact of immunoparesis at diagnosis on outcomes in symptomatic multiple myeloma (MM) remains unclear. We reviewed medical records of 147 MM patients at Beijing Chao Yang hospital. Most patients exhibited immunoparesis at diagnosis (84%). After a median follow-up of 27 months (range 1-78 months), in the group with immunoparesis at diagnosis, there was a very significantly shorter progression-free survival (PFS) than in the group without immunoparesis (estimated PFS of not reached vs 25 months, P = 0.001). Patients with suppressed Immunoglobulins (Igs) had the tendency to have a shorter OS than patients without suppression (estimated OS of not reached vs 38 months, P = 0.06). In multivariate analysis, the negative impact of immunoparesis on PFS was confirmed. In addition, achievement of both at least VGPR and at least CR was significantly higher in patients with preserved uninvolved Igs than in those with suppression of at least one uninvolved Ig. However, the negative impact of immunoparesis on response was not confirmed in a multivariate analysis. These results suggest immunoparesis in patients with symptomatic MM at diagnosis is an independent poor prognostic factor for upfront bortezomib-containing regimen.

Risk factors for infections in newly diagnosed Multiple Myeloma patients: A Danish retrospective nationwide cohort study.

OBJECTIVES: Infections pose the greatest risk of early death in patients with Multiple Myeloma. However, few studies have analyzed the risk factors for infections in Multiple Myeloma patients. The aim of this study was to analyze the risk factors infections within a population-based MM cohort. METHODS: Using Danish registries (from 2005 to 2013), we analyzed all ICD-10 codes for infections within the first 6 months of Multiple Myeloma diagnosis in 2557 patients. RESULTS: Pneumonia and sepsis represented 46% of infections. Multivariable regression analysis showed that risk factors for pneumonia were male gender (HR 1.4; P = 0.001), ISS II (HR 1.6; P = 0.0004) and ISSIII (HR 1.8; P = 0.0004) and elevated LDH (HR 2.6; P = 0.0008). Risk factors for sepsis were high bone marrow plasma cell % (HR 1.1; P = 0.038), ISS II (HR 1.7; P = 0.007) ISS III (HR 2.0; P = 0.002) and creatinine (HR 2.1; P = 0.002). Neither immunoparesis (hypogammaglobulinemia) nor comorbidity was significant risk factors. CONCLUSIONS: Our study suggests that tumor burden and renal impairment are risk factors for pneumonia and sepsis in the early phase of Multiple Myeloma.

Characteristics and prognosis of patients with non-immunoglobulin-M monoclonal gammopathy of undetermined significance: a retrospective study.

Non-immunoglobulin (Ig)-M monoclonal gammopathy of undetermined significance (MGUS) is a precursor lesion with the potential to evolve into a malignant plasma cell neoplasm. The prevalence of MGUS differs by ethnicity and is lower in the Japanese population than in the Western population. However, there is limited evidence about the clinical course of MGUS in Asian races. The present study aims at elucidating the clinical course and prognosis of Japanese patients with non-IgM MGUS in the clinical setting. We retrospectively examined 1009 patients with non-IgM MGUS identified by screening procedures. The median overall survival of these patients was > 20 years, and only one-fifth patients died of plasma cell neoplasms. The cumulative incidence of plasma cell neoplasms requiring treatment was 19%. Multivariate analysis revealed that immunoparesis and female gender were independent factors affecting treatment requirement. Although the characteristics and clinical course of patients with non-IgM MGUS obtained in this study were found to be essentially similar to those of previous studies, we report here for the first time that female gender is a significant independent factor for requiring treatment.

Immunoparesis and polyclonal immunoglobulin recovery after auto-SCT for patients with multiple myeloma treated at a single institution.

Immunoparesis and polyclonal immunoglobulin recovery have been recently described as common indicators of immune dysfunction in patients with multiple myeloma. In the present study, we aimed to assess the impact of immunoparesis and polyclonal immunoglobulin recovery at day-100 post autologous stem cell transplant (auto-SCT) on clinical outcomes. A total of 302 patients were included for the analysis of immunoparesis, and 197 were evaluable for polyclonal immunoglobulin recovery evaluation. Immunoparesis was observed in 93.5% of cases, with 47% of cases having polyclonal immunoglobulin recovery at 12 months post auto-SCT. Median overall and progression-free survival were longer in the group of patients with complete or partial normalization of polyclonal immunoglobulins. Patients receiving consolidation had a lower level of polyclonal reconstitution. In conclusion, polyclonal immunoglobulin recovery by 12 months post-auto-SCT is associated with superior overall and progression free survival in patients with MM. Efforts to better enhance polyclonal recovery deserve further investigation.