Infections In Multiple Myeloma Patients Research Articles

Cytokine-responsive T- and NK-cells portray SARS-CoV-2 vaccine-responders and infection in multiple myeloma patients

Patients with multiple myeloma (MM) routinely receive mRNA-based vaccines to reduce COVID-19-related mortality. However, whether disease- and therapy-related alterations in immune cells and cytokine-responsiveness contribute to the observed heterogeneous vaccination responses is unclear. Thus, we analyzed peripheral blood mononuclear cells from patients with MM during and after SARS-CoV-2 vaccination and breakthrough infection (BTI) using combined whole-transcriptome and surface proteome single-cell profiling with functional serological and T-cell validation in 58 MM patients. Our results demonstrate that vaccine-responders showed a significant overrepresentation of cytotoxic CD4+ T- and mature CD38+ NK-cells expressing FAS+/TIM3+ with a robust cytokine-responsiveness, such as type-I-interferon-, IL-12- and TNF-α-mediated signaling. Patients with MM experiencing BTI developed strong serological and cellular responses and exhibited similar cytokine-responsive immune cell patterns as vaccine-responders. This study can expand our understanding of molecular and cellular patterns associated with immunization responses and may benefit the design of improved vaccination strategies in immunocompromised patients.

Circulating Exosomal miRNA Signature As a Potential Risk Factor for DNA Virus Infection in Patients with Multiple Myeloma

Introduction DNA virus infection is a significant cause of morbidity and mortality in patients with multiple myeloma (MM). Monocyte dysfunction in MM patients plays a central role in infectious complications, but the precise molecular mechanism underlying the reduced monocyte resistance to viruses and risk factors for infection in newly diagnosed MM patients remains to be elucidated. Methods To determine the role of exosomal miRNAs in DNA infection of MM patients, we analyzed miRNAs in BM exosomes from MM patients (Exo-miRs) using high-throughput small RNA sequencing. To further evaluate the effect of these five upregulated Exo-miRs in antiviral response, we transfected the host cells with chemically synthesized miRNAs mimics to overexpress miRNAs. We utilized qPCR and WB to characterize the fate the cGAS-STING signaling pathway of THP-1 after overexpress miRNAs. The efficacy and safety of these Exo-miRs in innate antiviral immunity were evaluated using 5TGM1 C57BL/KaLwRij mice models. Additionally, miRNAs copy number as well as the viral susceptibility of newly diagnosed MM patients were determined in 82 samples from newly diagnosed biopsy proven MM patients. Results Screening of miRNAs enriched in exosomes delivered by primary MM cells identified five miRNAs as inhibitory factors that negatively regulate the cGAS-STING antiviral immune response. When engraftments of 5TGM1-Luc cells via tail vein for eight weeks in C57BL/KaLwRij mice resulted in MM progression with typical MM phenotypes, model mice were primed with Exo-miR antagomiRs oligonucleotides mixture through tail vein injection three times every 24 h followed by Murine cytomegalovirus (MCMV) challenge for 36 h. Consistent with the immunosuppression in MM patients, 5TGM1 C57BL/KaLwRij mice showed lower IFN-β in sera. Notably, intravenous administration of antagomiRs against miRNAs resulted in a marked increase of IFN-β levels in serum and IFN-I expression in organs (Figure 1). To investigate the potential of the miR-score as a prognostic determinant of vulnerability to DNA virus infection, we compared the miR-score in plasma exosomes collected from 82 newly diagnosed biopsy proven MM patients. We classified the viral susceptibility of newly diagnosed MM patients into two groups: I, DNA virus infection; II, no DNA virus infection. In human, a pronounced inverse correlation between IFN-β production by DNA virus in PBMCs and the microRNA (miR)-score of the exosomes within the plasma. The patients with DNA virus infection showed significantly enhanced circulatory expression of miRNAs than without DNA virus infection (p<0.001) patients. The diagnostic potential of miRNAs was assessed by plotting ROC curve, 5 miRNAs showed optimum sensitivity and specificity（AUC 0.854, P<0.0001, Sensitivity 87.5%, Specificity 74.1%, Cut-off values 5.234)（Figure 2）. Conclusions These findings identify a mechanism by which MM cells can suppress the host's innate immunity and potentially lead to immunocompromise in MM patients. Furthermore, the aberrant expression of specific miRNAs in MM patients emerges as a potential therapeutic target in MM cells. By quantifying miRNA scores based on abundant exosomal miRNAs in peripheral blood, the risk of DNA virus infection in MM patients can be assessed. Our findings shed light on a previously unknown molecular mechanism underlying immunosuppression in MM patients who have not received antineoplastic therapy, and also reveal a distinct miRNA signature that serves as a crucial determinant of the susceptibility of newly diagnosed MM patients to DNA virus infections.

COVID-19 Vaccine Acceptance/Hesitancy and Influence on Infection in Patients with Multiple Myeloma: A National-Wide Multicenter Survey in China

Background Patients with multiple myeloma (MM) are immunocompromised due to impaired humoral and cellular immunity in addition to immunosuppressive therapy. The situation and protective effects of severe coronavirus disease 2019 (COVID-19) vaccination in MM patients are not clarified. The study aimed to explore the reasons of COVID-19 vaccine hesitancy and its influence on severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection in MM patients during COVID-19 Omicron BA.4/5 subvariant outbreak in China. Methods An anonymous online questionnaire designed by our team was distributed to MM patients national-wide from December 26, 2022, to April 20, 2023. Then content of questionnaire included the contents of disease status, vaccination and SARS-COV-2 infection. Results A total of 508 valid questionnaires from 30 provinces were collected all over China. The vaccination rate of COVID-19 in MM patients was only 34.1% (n=173). The overall infection rate was 57.2%. Multivariate analysis showed that demographic characteristics were not factors affecting vaccination, while those accomplishing autologous stem cell transplantation (ASCT) presented a lower vaccination rate (20.2% vs. 48.4%, P<0.001). In the survey of vaccine acceptance/hesitancy, voluntary choice (49%), concerns to COVID-19 infection (35.1%), and trust of vaccine efficacy (26.5%) were the three main reasons for receiving vaccines. Physicians' suggestion (52.0%), conflicts of MM treatment (37.8%) and concerns about MM progression (31.3%) were the top three reasons for vaccine hesitancy. Adverse events (AEs) after vaccination were mainly myalgia or joint pain, fatigue and erythema or swelling at the site of injection. No MM disease-related adverse effects were reported. Among 104 vaccinated MM patients with SARS-COV-2 infection, the median time since last vaccines to infections was 304 days (range 4-593). The infection rates between the vaccinated population (n=173) versus non-vaccinated ones (n=335) were 60.1% vs. 55.8% respectively (P=0.35). In subgroup analyses, the infection rates in vaccinated patients were lower than those in unvaccinated ones including the elderly (49.3% vs. 55.2%), obese patients (BMI≥28) (50% vs. 63.3%), and R/RMM population (42.2% vs. 66.7%, P=0.005). The proportion of hospitalized patients due to SARS-COV-2 infection in vaccinated group was significantly lower than that in unvaccinated group (4.8% vs.12.3%, P=0.038). Conclusions Vaccine hesitation is common in Chinese MM patients although inactivated COVID-19 vaccine only causes mild AEs. Lower infection rate in MM patients is probably due to strict self-quarantine. COVID-19 vaccination is not translated into less SARS-COV-2 infections, but does protect the elderly, obese or R/RMM patients from severe infections. Clinicians are suggested to encourage MM patients to receive COVID-19 vaccines for the sake of reducing severe infections and related mortality. Keywords Questionnaire; Multiple Myeloma; vaccination; SARS-COV-2; outbreak infection

IVIg Use Associated with Ten-Fold Reduction of Serious Infections in Multiple Myeloma Patients Treated with Anti-BCMA Bispecific Antibodies.

To the best of our knowledge, this is the first study to comprehensively analyze risk factors and mitigation strategies to prevent infections in myeloma patients receiving anti-BCMA bispecific antibodies. Profound and prolonged hypogammaglobulinemia was universal among responders, while immunoglobulin replacement was associated with 90% lower rates of grade 3-5 infections. See related commentary by Garfall and Stadtmauer, p. 427 . This article is featured in Selected Articles from This Issue, p. 419.

Clinical Features and Risk Stratification of Multiple Myeloma Patients with COVID-19.

SARS-CoV-2 infection often results in a more severe COVID-19 disease course in multiple myeloma (MM) patients compared to immunocompetent individuals. The aim of this report is to summarize the clinical features of the MM patients with COVID-19 and the impact of MM treatment on outcomes to guide risk stratification and ensure the appropriate management of the patients. Serological responses in MM patients post-infection or -vaccination are also reviewed to better understand the strategy of prevention. Along with reports from the literature, we presented findings from a retrospective analysis of the clinical characteristics and outcomes of COVID-19 infection in MM patients in our institution. Study population includes 34 MM patients with a median age of 61 (range: 35-82 years) who tested positive for SARS-CoV-2 between 1 March 2020-15 August 2021. We examined the effect of chemotherapy, the benefit of neutralizing monoclonal antibody (Bamlanivimab) and the impact of anti-CD38 antibody (daratumumab) on the hospitalization and mortality of the patients, as well as the efficacy of native antibody production. Our results showed that MM patients have increased hospitalization and mortality rates from COVID-19 compared with that of general population, especially those on active chemotherapy. Advanced age, high-risk myeloma, renal disease, and suboptimal disease control are independent predictors of adverse outcomes. The use of daratumumab does not increase the disease severity/hospitalization or the post-infection/vaccination seropositivity of SARS-CoV-2. The neutralizing antibody decreases overall mortality. Evidence from the current study and previous publications suggest that testing of neutralizing antibody post-SARS-CoV-2 vaccination in MM patients may be needed in reducing COVID-19 risk.

P54 ORAL ANTIVIRALS RITONAVIR-NIRMATRELVIR AND MOLNUPIRAVIR ARE HIGHLY EFFECTIVE IN PATIENTS WITH MULTIPLE MYELOMA AND COVID-19; A SINGLE-CENTER, PROSPECTIVE STUDY

Severe SARS-CoV-2 infection is characterized by an initial viral phase, often followed by a severe inflammatory phase. In patients with multiple myeloma (MM), SARS-CoV-2 infection has been associated with severe clinical course and high mortality rates, due to the concomitant disease and treatment-related immunosuppression. Moreover, MM patients do not seem to respond well to vaccination despite adequate immunization, especially those who are on treatment with anti-CD38 or anti-BCMA therapies. Thus, MM patients are at a higher risk for breakthrough infection compared with noncancer patients or patients with solid tumor and supportive treatment with prophylactic use of monoclonal antibodies against SARS-CoV-2 is needed. At the time of COVID-19 infection, the use of antiviral therapy is necessary. Specific antiviral treatment involves viral replication control with monoclonal antibodies and antivirals, including molnupiravir and the ritonavir-boosted nirmatrelvir. Molnupiravir is the prodrug of the ribonucleoside analogue β-D-N4-hydroxycytidine, which inhibits the SARS-CoV-2 replication and reduces viral load. In phase I/II/III studies, it has shown both safety and efficacy, reducing the risk of hospitalization and mortality by approximately 50% in non-hospitalized adults with mild-to-moderate COVID-19 disease who are at risk for poor prognosis. Ritonavir-nirmatrelvir is an oral protease inhibitor that has also reduced the hospitalization and death in clinical trials by approximately 90%. Although available evidence supports the use of antivirals in patients with SARS-CoV-2 infection to prevent severe disease, relevant data on MM patients is scarce. The use of specific antiviral treatment with molnupiravir and ritonavir-boosted nirmatrelvir aims to reduce severe infection and hospitalization in patients with MM, who undergo mild SARS-CoV-2 infection and do not require supplemental oxygen. This prospective study investigates the effect of these two agents on SARS-CoV-2 infection severity and mortality in patients with MM. Patients received either ritonavir-nirmatrelvir or molnupiravir. Consecutive patients with MM and SARS-CoV-2 infection were prospectively enrolled in the study. All patients had microbiologically confirmed SARS-CoV-2 with polymerase chain reaction (PCR). The patients received either ritonavir-nirmatrelvir or molnupiravir according to the national guidelines for five days. Treatment with antivirals was initiated within the first five days from SARS-CoV-2 infection symptoms onset in patients with no need of supplemental oxygen. All patients were at high risk for severe SARS-CoV-2 infection due to the underlying MM. Baseline demographic and clinical characteristics, as well as levels of neutralizing antibodies (NAbs) were collected and compared. The effect of different treatments on SARS-CoV-2 infection severity and mortality was examined. A total of 169 patients infected with SARS-CoV-2 were included. 74 of them were females with an average age of 64.4 years and a mean Body Mass Index (BMI) of 26.91 kg/m2. Regarding their medical history, 14 patients (8.3%) were diagnosed with diabetes mellitus (DM), 71 (42%) had hypertension, six (3.6%) had coronary artery disease (CAD) and 16 (9.5%) had chronic obstructive pulmonary disease (COPD). All patients except for one, were vaccinated, mostly with BioNTech Pfizer vaccine (96.4%). 153 patients had already received 3 doses, seven (7) had received four (4) doses and eight (8) had received two (2) before COVID-19 diagnosis. Regarding treatment, several drug combinations were administered to patients depending on their medical condition and history of MM. These included proteasome inhibitors based regimen, immunomodulatory drugs based regimen, anti-CD38 monoclonal antibody based regimen, anti-BCMA based regimen, and other treatments, such as selinexor and cyclophosphamide. For most of the patients, specifically for 100 of them, this was the 1st line of treatment, for 36 the 2nd, for 16 the 3rd, for 7 the 4th and for 3 patients the 5th line of treatment. As far as the SARS-CoV-2 infection is concerned, 139 patients (82.2%) were treated with ritonavir-nirmatrelvir while the remaining 30 patients (17.8%) with molnupiravir. The duration of antiviral treatment was equal to five (5) days in all but three (3) cases. In total, 149 (88.2%) patients had mild infection, 15 (8.9%) had moderate infection, and five (5) (3%) had a severe one. Severe cases were treated differently, as expected, compared to mild or moderate cases. The special treatment included hospitalization in 6.7% of patients with moderate infection (1 patient) and 100% of patients with severe infection (5 patients), tocilizumab in 5 patients with severe infection, intubation in 2 patients severely infected (40% of patients with severe infection) and corticosteroids in 13 patients with moderate infection (86.7% of these patients) and 5 with a severe one (100% of these patients). An exception was observed regarding use of corticosteroids since it appears that they were given almost equally in patients with moderate and severe outcomes. As far as the antiviral drug type is concerned, no difference in mild, moderate or severe infection was observed (p=0.236). Regarding BMI, age or medical history defined as the presence of DM, COPD, CAD or hypertension no statistically significant difference was observed in the outcome of the infection. Regarding PS, a statistically significant difference of mild versus severe cases was observed (p=0.041), while the difference between mild and moderate cases was borderline non-significant (p=0.052). A difference between severe and mild cases was observed concerning neutralizing antibody response levels before SARS-CoV-2 infection. Patients with severe disease appeared to have lower neutralizing antibody levels before SARS-CoV-2 infection compared to patients with mild disease (p=0.04). The mean and standard deviations for NAbs levels were 67.49%±28.85%, 59%±24.69% and 35.4%±37.57% for the groups of mild, moderate, and severe outcomes respectively. Regarding treatment, despite the various drug types included in the study and their combinations, it was observed that treatment with belantamab mafodotin was significantly related to the outcome. There was a statistically significant higher risk for severe SARS-CoV-2 infection (p<0.001) according to the Fisher’s exact test. In conclusion, the Covid-19 pandemic is a major cause of mortality worldwide and patients with MM are at high risk for severe infection. Unfortunately, the infection cannot be completely controlled, although many antiviral drugs have shown promising therapeutic results. The majority of immunocompromised patients may not be fully protected after vaccination and the use of oral antiviral drugs in case of infection seems to be effective. Ritonavir-nirmatrelvir and molnupiravir seem to be highly effective in preventing severe disease and mortality from SARS-CoV-2 infection in MM patients who are under treatment for the underlying disease. This prospective study indicates the comparable effects of the two treatment options providing an important background for further research.

[Infection risks and prevention in patients with multiple myeloma].

Multiple myeloma (MM) is a hematological malignancy characterized by aberrant clonal plasma cells in the bone marrow. Despite significant advances in the treatment of MM, infection remains a main cause of death. MM patients have an increased risk of infection compared to their healthy counterparts due to several factors related to underlying disease, advanced age, comorbidities, and MM treatment. MM patients are at high risk of infection during the first 3 months after diagnosis and during relapse. Anti-myeloma drugs frequently result in severe immunosuppression and increased risk of infection. Proteasome inhibitors deplete T cells, lenalidomide and pomalidomide induce neutropenia, and CD38 antibodies reduce B cell function. To prevent infection in MM patients, we should take appropriate action by medical prophylaxis and vaccination.

2101. CMV Infections in Multiple Myeloma Patients

Abstract Background Substantial progress in the treatment of multiple myeloma (MM) has led to improved patient outcomes and prolonged survival of patients. These therapeutic advances have resulted in increased cumulative immunosuppression leading to increased susceptibility to opportunistic infections including CMV infection. The significance of CMV infection in MM patients is not well understood. We sought to describe the clinical characteristics and outcomes of patients with MM who develop CMV infection. Methods Retrospective chart review of MM patients at Mount Sinai Hospital in NY who had CMV DNA PCR sent. The Mount Sinai Multiple Myeloma Database was utilized to identify patients who developed CMV viremia. Demographic, clinical and laboratory data were abstracted from electronic medical records. IRB approval was obtained. Statistical Analysis Factors associated with 30-day mortality by univariate analysis were evaluated using Fischer’s exact and Wilcoxon rank-sum test. Results Demographics 414 MM patients had CMV PCR sent at least once. Forty-six cases of CMV infection were identified. CMV Infection Characteristics Forty-six patients were found to have CMV viremia, defined as PCR &amp;gt;500 IU/mL. Twenty-two (47%) had symptomatic infection. One patient had CMV pneumonitis and in 7/46 (15%) patients, CMV end-organ disease was suspected. Twenty (43%) patients had progressive disease status, 73% had prior history of autologous stem cell transplant and 85% had received steroids within 30 days of CMV infection. Twenty-nine (63%) patients had concurrent infections within 30 days of CMV infection, including bloodstream infection (n=16), bacterial pneumonia (n=9), respiratory viral infection (n=6), infectious colitis (n=5), and fungal infection (n=3). Outcomes 9/46 (19%) patients died within 30 days of CMV infection and 12/46 (26%) required ICU admission during that hospitalization. In univariate analysis of risk factors associated with mortality, higher weekly steroid dose approached statistical significance (p=0.06) and peak CMV PCR &amp;gt;1000 IU/mL (p.008) was associated with lower mortality. Conclusion CMV infection is associated with morbidity and mortality in MM patients. Prospective studies are needed to better assess the clinical significance of CMV reactivation in this population. Disclosures Emily Baneman, MD, Merck: Grant/Research Support.

Predicting Risk of Infection Based on Immunoglobulin Nadirs after CD38 Monoclonal Antibody Treatment in Multiple Myeloma

Background: Anti-CD38 monoclonal antibodies are used to treat newly diagnosed and relapsed or refractory multiple myeloma. Previous studies have shown an increased risk of infection while on daratumumab due to the immunosuppressive effect on malignant and normal plasma cells. We sought to retrospectively analyze and further understand the correlation of immunoglobin levels and risk of infection during treatment with anti-CD38 monoclonal antibodies in Multiple Myeloma. Methods: Analysis was performed on data from 261 patients who had received anti-CD38 monoclonal antibody therapy as part of treatment for multiple myeloma between November 11, 2016, and May 11, 2022. 51.7% were male and 48.3% were female. 47.1% of the patients identified as Black, 46% as White, and 6.9% as other races. 14.9% of the patients had Stage I, 41.8% had Stage II and 17.2% had Stage III disease, based on the Revised International Staging System (RISS). Baseline renal disease was present in 35.6% of patients. Median number of anti-CD38 Monoclonal antibody infusions was 16. We examined rates of specific infections (determined by ICD-10 codes), including pneumonia, urinary tract infection, bacteremia, and sepsis, as well as emergency room visits, hospitalizations including ICU stays for up to a year after completing treatment. These rates were correlated with immunoglobulin levels, absolute lymphocyte count, and the presence of concomitant treatment with a proteasome inhibitor or immunomodulator. Results: The overall infection rate among patients receiving anti-CD 38 monoclonal antibody treatment was 32.6%. Bacterial infection developed in 22.2%, viral infections in 17.6%, and fungal infections in 3.4% of patients. SARS-CoV-2 infection rate was 13.4%. The median number of infusions was 15 in those without an infection and 20 in those who developed an infection (p<0.001).19.2% of patients who began anti-CD38 monoclonal antibody treatment during the study period have expired, of whom 56.0 % had an infection. Higher rates of infection were noted with lower IgA levels (p=0.007). There was no significant difference in infection rate with lower IgG and IgA levels or lower absolute lymphocyte levels (p=0.054). However, in patients with an infection there was a longer duration of sub-normal IgG days (114 vs 287 days, p=<0.001), IgA (119.5 vs 215, p=0.006), and IgM (161 vs 274.5, p=0.011). 44.4% of patients had an emergency room visit of whom 40.0% were due to infections (p=0.113). 66.9% of patents required hospital admissions of whom 43.2% had an infection) p<0.001). 18.5% of treated patients required ICU stays of whom 63.9% had an infection) p<0.001). Discussion:Conclusions: A longer duration of subnormal Immunoglobulin levels correlated with higher risk of infection in Multiple Myeloma patients treated with anti-CD 38 monoclonal antibodies. Lowest Ig A levels during treatment correlated with a higher rate of infection while lowest IgG levels did not. Patients who developed infectious complications while on treatment with anti-CD 38 monoclonal antibodies had a significantly higher risk of hospitalization, ICU stays, and death. Prophylactic intravenous immunoglobulin can be studied to evaluate mitigation of infection in the highest risk subpopulation identified in this analysis such as those with prolonged subnormal Immunoglobulin levels. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Timing and Nature of Infections in Multiple Myeloma Patients Treated with Anti-BCMA CAR-T Cells

Introduction: Anti-BCMA CAR-T is a highly effective therapy approved for relapsed/refractory multiple myeloma (MM). Its main toxicities include cytokine release syndrome, neurotoxicity, and cytopenias. Infections are common but not well-studied in this population. In this study, we seek to characterize the timing and nature of infections to better inform appropriate prophylactic measures. Methods: We retrospectively reviewed all MM patients (pts) treated with anti-BCMA CAR-T at Mount Sinai from 2018-2022. Data were collected on baseline characteristics, treatment, disease response, hypogammaglobulinemia (HGG), infections, and prophylactic measures, including intravenous immunoglobulin (IVIg). The study period was from time of CAR-T infusion until progression or death. Chi-squared analysis was used for univariate associations and the Kaplan-Meier method was used for time-to-event calculations. Incidence rates ratios (IRR) were calculated using the exact Poisson method. This study was approved by the Mount Sinai IRB. Results: 80 pts were treated with anti-BCMA CAR-T; the median age was 61 years (range 35-77) and 40% were female. The median time from diagnosis to treatment was 5.1 years, with a median of 5 prior lines of therapy (range 1-18). 71% had high risk cytogenetics, and pts had a median of 2 infections (range 0-8) in the year prior to CAR-T. IVIg was used prophylactically in 95% of pts, usually for at least the first 6 months, and these pts were on IVIg 49% of the total time on study. All patients received prophylaxis for VZV, PCP (if CD4< 200/mm3), and anti-bacterial plus anti-fungal for ANC <500/mm3. Median follow-up was 30.1 months, with ORR of 94%, median PFS of 18.8 months and estimated OS of 70% at 3 years. CRS occurred in 86% (6% grade 3/4), with tocilizumab used in 73% and steroids in 34%. There were a total of 207 infections during 1336 months of follow-up (1.9 per pt-year), including 57 grade 3-5 infections (0.5 per pt-year) among 25 (31%) pts, and 5 (6%) deaths, with infection rates highest in the first 3 months (Figure 1). Deaths from infection occurred at months 3 (bacterial osteomyelitis), 4.6 (COVID-19), 5.3 (bacterial pneumonia), 24.4 (bacterial skin/soft tissue), and 26.4 (fungemia). Infections (all-grade/ grade 3-5) were mostly in the respiratory tract (63%/43%), followed by GI (11%/32%), skin/soft tissue (5%/11%), and bloodstream (5%/21%), and were mostly viral (68%/38%), followed by bacterial (30%/63%) and fungal (2%/5%). Few opportunistic infections occurred, including grade 3 Cryptosporidiosis, grade 3 Citrobacter sedlakii bacteremia, grade 5 Parabacteroides distasonis abscess and osteomyelitis, and grade 5 Saccharomyces fungemia. Of those with follow-up since 2020, 16 (25%) tested positive for SARS-CoV-2, with 4 severe cases including 1 death at 4.6 months (of these, 2 were vaccinated, including the patient who died). Asymptomatic CMV reactivation occurred in 34% and was only treated in 3 patients. 95% developed HGG, with severity difficult to gauge due to routine IVIg use. Immunoglobulin (Ig) recovery occurred at 14.3 months for one uninvolved Ig and 20 months for two uninvolved Igs. Absolute neutrophil count <500/mm3 and absolute lymphocyte count <500/mm3 were each associated with more severe infections (p<0.001). The 26 pts with 1-3 prior lines of therapy (LoT), compared with those with 4+ LoT, had lower overall infection rate (1.68 per pt-year vs 2.42 per pt-year, IRR 0.70, 95% CI [0.51-0.94], p=0.0.013) and grade 3-5 infection rate (0.29 per pt-year vs 0.62 per pt-year, IRR 0.46, 95% CI [0.21-0.91] p=0.016). Discussion: Infections among pts treated with anti-BCMA CAR-T were predominantly viral and occurred in the highest rates in the first 3 months. Neutropenia and lymphopenia, common in the first 3 months, were each associated with more severe infections, emphasizing the need for intensive prophylaxis and close outpatient monitoring during this period. Fungal and other opportunistic infections were rare, although one vaccinated patient died of COVID-19, highlighting the need for passive immunity in this population. Ig recovery occurred at 14.3 months, so the optimal duration of IVIg prophylaxis remains an open question. Of note, pts treated in earlier lines of therapy had significantly fewer infections, including grade 3-5 infections. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Inadequate Sars-Cov-2 Vaccine Effectiveness in Patients with Multiple Myeloma: A Large Nationwide Veterans Affairs Study

IntroductionCoronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, is particularly serious in patients with multiple myeloma (MM), with estimated mortality of over 30% in several studies. In the general population, SARS-CoV-2 vaccination has been demonstrated to be an effective approach to preventing infection. However, patients with MM were not included in vaccination trials. Recent studies suggest that patients with compromised immune systems exhibit reduced antibody response to SARS-CoV-2 vaccination, and MM patients are often immunocompromised both due to MM itself and due to MM treatment. Thus, the objective of this retrospective cohort study in the national Veterans Affairs (VA) healthcare system was to evaluate the real-world effectiveness of SARS-CoV-2 vaccination to prevent COVID-19 infection in MM patients during the 140-day period following initial vaccine availability.MethodsThis is a multicenter study of SARS-CoV-2 infection among vaccinated and unvaccinated patients at VA hospitals nationwide during the period from 12/15/2020 to 5/4/2021. We identified a cohort of MM patients who were alive and without prior SARS-CoV-2 infection on their date of vaccination or inclusion as a control. For added comparison with a less immunocompromised population, we also identified a cohort of cancer survivors, defined as patients with any solid or hematologic malignancy who had been treated with systemic cancer-directed therapy subsequent to 8/15/2010, but had not been treated with such therapy in the 6 months prior to vaccination or inclusion as a control, and were alive and without prior SARS-CoV-2 infection on that date. Vaccinated patients were exactly matched 1:1 to unvaccinated controls on race, VA facility, rurality of home address, cancer type, and treatment timing and modality with minimum distance matching on age. The primary exposure was receipt of a SARS-CoV-2 vaccine. The primary outcome was laboratory-confirmed SARS-CoV-2 infection. Vaccination effectiveness was defined as 1 minus the risk ratio of SARS-CoV-2 infection for vaccinated individuals compared to unvaccinated controls.Results6,891 MM patients met eligibility criteria and 4,367 were vaccinated during the study period. Of those, 1,606 vaccinated MM patients were matched 1:1 to 1,606 unvaccinated or not yet vaccinated controls. In addition, for comparison, 2,476 vaccinated cancer survivors were matched 1:1 to 2,476 unvaccinated or not yet vaccinated controls. Median follow-up was 44 days among MM patients and 46 days among cancer survivors. Vaccine effectiveness in the matched cohort of MM patients was 22.2% (95% CI, -133 to 82.7%) starting 14 days after the second dose. In contrast, effectiveness was 82.3% (95% CI 16.4 to 100%) starting 14 days after the second dose in the matched cohort of cancer survivors. Among vaccinated MM patients in the matched cohort, 14 (8.7 per 1000 patients) were infected with SARS-CoV-2 subsequent to vaccination. Among vaccinated cancer survivors in the matched cohort, 10 (4.0 per 1000 patients) were infected subsequent to vaccination.ConclusionVaccination is an effective strategy for preventing SARS-CoV-2. However, effectiveness may be reduced in patients with MM, likely due to a co-existing immunosuppression both due to the disease process as well as associated therapy. Future studies are needed to evaluate the relationship between MM disease states, types of therapy used and treatment timing that may impact vaccine effectiveness, and to also determine if MM patients would benefit from post-vaccination serologies or a booster vaccination. DisclosuresBranch-Elliman: Gilead Pharmaceuticals: Research Funding. Brophy: Novartis: Research Funding. Munshi: Pfizer: Consultancy; Legend: Consultancy; Novartis: Consultancy; Adaptive Biotechnology: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Abbvie: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Bristol-Myers Squibb: Consultancy.

OAB-046: COVID-19 infection in multiple myeloma patients – retrospective analysis of 371 Czech patients

BackgroundCOVID-19 disease caused by SARS-CoV-2 coronavirus has affected millions of people worldwide. The mortality of this infection varies with age and comorbidities up to more than 10% in very elderly population. The aim of our study was to determine the disease pattern and mortality rate among multiple myeloma patients.MethodsWe retrospectively analyzed entries in the Czech Registry of Monoclonal Gammopathies from patients who were infected with SARS-CoV-2 from March 2020 until May 2021. Demographic data, treatment patterns, comorbidities, symptoms of COVID-19, treatment modalities and healthcare utilization was compared in survivors and non-survivors.ResultsOverall, 371 patients with MM and COVID-19 infection were identified. Median age at covid-19 diagnosis was 69 years (37-91 years), 53.4% (198/371) were males. There were 70.1% (260/371) survivors and 20.8% (77/371) deceased patients, outcome of 9.2% (34/371) of patients is unknown. PCR positivity was seen with median 20 days (1-84 days) in 79 evaluable patients. 6 patients were vaccinated prior to infection (5-68 days). Infection was acquired during actual treatment in 53.1% of patients (197/371). Median number of previous lines administered was 1 (0-7). Treatment preceding infection was most frequently composed of lenalidomide in 50.3%, bortezomib in 42.1% and daratumumab in 19.8%. Symptomatic infection was seen in 74.9% (278/371) of patients with fever being the leading symptom (49.6%) followed by cough (39.1%) and shortness of breath (35.0%). Inpatient treatment was needed in 45.0% (167/371) of patients, intensive care unit was required in 38.9% (65/167) of patients. Median length of in-hospital stay was 11 days (1-53 days). Artificial lung ventilation was necessary in 10.8% (18/167) patients, 24.6% (41/167) needed non-invasive ventilation or high flow oxygen and 35.3% (59/167) of patients needed low flow oxygen. Remdesivir was administered to 10.0% (37/371) and convalescent plasma to 4.9% (18/371) of patients. No difference was seen in mortality according to ISS stage (p=0.609), administered lines of therapy (p=0.119) or achieved treatment response (p=0.418).ConclusionsThe mortality of MM patients with COVID-19 was very high (20.8%). Healthcare utilization was high with almost half of the infected myeloma patients needing inpatient treatment. No apparent risk factors in terms of disease status or previous treatment were identified. Supported by MH CZ - DRO (UHHK, 00169906) and by the program PROGRES Q40/8.

Compliance With Vaccination Recommendations Among Patients With Multiple Myeloma: A Real World Experience.

Infections are the second leading cause of death in multiple myeloma (MM), after the disease itself. A large retrospective population-based study revealed a 7-fold higher risk for bacterial and a 10-fold increased risk for viral infections in MM patients compared with population-based controls and showed a particularly high risk shortly after start of therapy.1 Hence, all available measures to curb this complication should be exploited. These include antibiotic prophylaxis in selected cases, antiviral prophylaxis of well-defined risk groups,2 and vaccination against several bacteria and viruses.3 Recently, recommendations for vaccination against various pathogens have been updated.3 In this study, we assessed the type of recommendations provided to MM patients in real-word clinical practice and their compliance with them. Moreover, we surveyed the incidence of infections before and after onset of antimyeloma therapy and patients’ willingness to be vaccinated against coronavirus disease 2019 (COVID-19). To capture the required information for this survey, we created a questionnaire (See Supplemental Digital Content, File 1, https://links.lww.com/HS/A165) that was specifically designed to assess the vaccination recommendations given to patients from their treatment institutions or physicians and to evaluate their compliance with the advice received. Furthermore, patients were asked about the incidence of infections the year before and the first 6 months after start of therapy and about their willingness to be vaccinated against COVID-19. The first draft was discussed with members of 3 MM support groups. Their comments and suggestions were incorporated in the questionnaire, which was circulated again for comments and suggestions. After approval of the modified questionnaire by the representatives of these patient groups, the instrument was published with an invitation to patients to participate as online tool on the homepages of 31 MM support groups in Germany, Switzerland, and Austria. In addition, 500 hardcopy versions of the questionnaire were mailed directly to patients, thereby reaching out to approximately 2000 patients. Three-hundred thirty-five patients with MM have completed the survey during November 24 and December 15, 2020. Results were analyzed by descriptive statistics and correlation analyses. Patients’ characteristics are shown in Table 1. Of note, the patients’ profile and their responses did not differ between respondents to the online or printed version of the questionnaire nor between patients from the 3 countries of origin. Patients’ median age was 65 years; the majority (75.4%) received high-dose therapy followed by autologous stem cell transplantation (ASCT) as first-line treatment. Less than 1 quarter (23.2%) had only 1 treatment line, while the majority had been exposed to 2 to 3 (35.1%), or to 4 or more (42.7%) prior treatment lines. Median time from start of first-line therapy to conduction of the survey was 5 years. One-hundred sixty-seven (51.7%) patients reported at least 1 infectious period in the year preceding the diagnosis of MM, 128 (39.6%) patients had 1 to 3, and 39 (12.1%) had 4 or more infectious episodes before start of antimyeloma therapy. During the first 6 months after initiation of first-line therapy, 181 (57.6%) patients reported none, 125 (39.8%) 1 to 3, and 8 (2.5%) 4 or more infectious episodes, respectively. Table 1 - Patient Characteristics. Patient Characteristics (n = 335) Median age (y; range) 65 (32–88) Country (DE/AT/CH; n = 324) 156 (48.1%)/130 (40.1%)/38 (11.7%) Gender (male/female; n = 333) 164 (49.2%)/169 (50.8%) Prior lines of therapy (n = 305) 1 70 (23.0%) 2–3 106 (34.8%) ≥4 129 (42.3%) Median time (y) since start of first-line therapy (range) 4.96 (0.04–27.97) ASCT (yes/no; n = 325) 245 (75.4%)/80 (24.6%) Infections During 12 mo Before Start of Therapy, n = 322 6 mo After Start of Therapy, n = 314 None 155 (48.1%) 181 (57.6%) 1–3 128 (39.8%) 125 (39.8%) ≥4 39 (12.1%) 8 (2.5%) ASCT = autologous stem cell transplantation; AT = Austria; CH = Switzerland; DE = Germany. Recently issued recommendations for vaccination of patients with MM are shown in Supplemental Digital Content, Tables 1–3, https://links.lww.com/HS/A165. The number of patients who received recommendations from their treatment centers and physicians for the various vaccinations and the proportion of patients who actually received the vaccine is shown in Figure 1. The vaccination recommendations varied widely depending on the type of vaccine, with influenza being the most frequently recommended vaccination (77.0%), followed by pneumococci (65.4%), diphtheria, tetanus, pertussis (DTP) (40.6%), hepatitis B (28.1%), and herpes zoster (28.1%), followed by tick borne encephalitis (TBE), hepatitis A, and mumps-measles-rubella (MMR). Thus, physician’s compliance with the recommendations for vaccination was variable but reflected clinical priority. Patients’ compliance with their physicians’ advice was remarkably high with good compliance rates (greater than 80%) for influenza, pneumococci, hepatitis B, and DTP. The rates of recommendations for influenza and pneumococci were higher than reported in a previous study for US myeloma patients4 and supported by clinical experience and data showing that upper and lower respiratory tract infections are the most frequently observed infectious complications in patients with MM.1 Upper respiratory tract infections disturb the complex equilibrium between commensal bacteria and viruses and facilitate the development of lower respiratory tract bacterial and viral infections,5 underlining the need for applying the available prevention strategies. These considerations are supported by the data of this survey that showed a high incidence of infectious episodes in the year before start of antimyeloma therapy, and during the first 6 months after initiation of treatment, with the latter being due to myeloma-induced immune suppression and toxicities of myeloma therapy.Figure 1.: Number of patients who received recommendations for a specific vaccine and proportion of patients who complied with the given advice. DTP = diphtheria, tetanus, pertussis; MMR = measles, mumps, rubella; TBE = tick borne encephalitis.The high percentage (75.4%) of patients with prior ASCT seems to explain that DTP and MMR vaccinations were recommended to many patients as several of them may lose anti-infective immunity after high dose therapy. Our data show that this advice to get vaccinated with these vaccines was readily taken up by the majority of patients. Vaccination with varicella zoster virus (VZV) vaccine was recommended to less than one-third of patients, which was lower than expected, since 2 studies in patients with hematological malignancies employing either the inactivated varicella zoster vaccine6 or the preferred adjuvanted recombinant zoster glycoprotein E vaccine7 showed substantial vaccine efficacy of 77.7% and 87.2% with the former and latter product, respectively. Clinicians are likely aware that VZV vaccination does not provide complete protection against VZV reactivations in patients particularly on treatment with proteasome inhibitors, which suppress the priming of naive T cells against viral antigens thereby increasing the susceptibility to viral infections.8 Daratumumab may also be associated with increased risk for reactivation of herpes viruses (herpes simplex virus, VZV, and cytomegalovirus) due to depletion of natural killer cells and possible other perturbations of antiviral defense mechanisms.9 Those patients should, irrespective of their vaccination status, receive anti-VZV prophylaxis.10 Vaccination against hepatitis B and A was proposed to 28.1% and 23.9% of patients, respectively. These lower numbers may be due to low exposure as these vaccines are recommended for MM patients travelling to areas of high endemicity, and to patients with behavioral and/or occupational exposure.3 Furthermore, hepatitis B vaccination should be considered only in patients who are negative for hepatitis B surface antigen and anti-hepatitis B core antigen antibodies. Those with one or both tests positive should be studied for the presence of hepatitis B DNA, and if positive should be treated with one of the newer oral antinucleoside analogs.11 Reactivation of hepatitis B infection has been reported to occur early after start but also after prolonged treatment and in patients exposed to ASCT. Vaccination with haemophilus influenzae type B (HiB) was recommended to 12.8% of patients only, a figure that is below expectations given the fact that only 67.4% complied with this advice. More than 50% of patients lack protective antihaemophilus influenza type B antibodies and serum bactericidal activity against HiB was found to be absent in 70% of patients.12 Hence, awareness about the potential benefits of HiB vaccination should be raised both on the side of care provider and in MM patients. TBE is endemic in several parts of the surveyed countries, which likely explains that slightly more than one-fourth (26.9%) of patients were advised to be vaccinated and that close to 80% of patients followed this recommendation. A recent report in patients with hematological malignancies after ASCT or allogeneic-SCT revealed seropositivity in 77% and 80% of patients, respectively, scheduled for 4 doses of a TBE vaccine.13 The relatively high acceptance rate of vaccinations by informed patients participating in this survey was manifested by their eager willingness to get vaccinated with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (82.5%), which is exemplary as compared with the general population of the United States and of Germany (the latter likely changing over time, while more have been vaccinated with good tolerance).14 Possible explanations for this proactive attitude in MM patients may be their higher individual risks for infections, high mortality rate in case of a SARS-CoV-2 infection,15 greater interest in relevant developments in medicine, closer contacts with health care personnel with frequent advise to get vaccinated, and being diagnosed with a serious disease, facts that increase the willingness to accept preventive measures and treatment. An inherent limitation of surveys, among others, is that only active and empowered patients are responding, leaving it open, whether the outcome would have been different in the nonresponding patient population, and thus possibly not representative of the entire patient population, Usually, elderly people are less likely to participate in surveys, which is also reflected by the median age of the respondents of 65 years in this study. Nevertheless the comparison of responses between patients aged ≥70 years with those obtained from the younger participants did not reveal any clinically relevant or statistically significant differences. Likewise, no significant associations were noted between individual patient characteristics, duration of disease, number of treatment lines, incidence of infections, and their compliance with vaccination advice. Finally, the vaccination practices observed in this MM patient cohort suggests that awareness of the positive effects of vaccinations should be raised both among treating physicians and patients, a notion especially important in pandemic/COVID-19 times. Acknowledgments We thank the willingness of myeloma patients to respond to the questionnaire and the self-help groups for their participation. Disclosures HL received research funding from Amgen and Takeda, as well as honoraria for speaker’s bureau/advisory boards from Amgen, Sanofi, Janssen, BMS-Celgene, and Seattle Genetics. ME has received clinical trial funding from Amgen, BMS, Janssen, Takeda; and speaker honoraria from Amgen, BMS, Janssen, Sanofi, and Takeda. AM has no conflicts of interest to disclose. Source of funding This work was supported by the Austrian Forum Against Cancer.

B-Cell Lymphoma Patients Have a 10% Risk of Shingles, 7% in Cutaneous T-Cell Lymphoma

Background: Patients with lymphoma can be immunosuppressed from the disease, treatment or both. One indicator of cellular mediated immunity is reactivation of Varicella Zoster (VZV), a painful viral infection estimated to occur to 30% of U.S. population during a lifetime and associated with a particularly morbid post-herpetic neuralgia. Bortezomib and dexamethasone have been shown to be correlated with increased rates of varicella zoster and other viral infections (Kim SJ et al, Clinical lymphoma & myeloma, 2008). Autologous stem cell transplant depletes cellular- and humoral-immunity (Kamber C et al, BMT, 2015). While the main risk factor for VZV reactivation is age (Harpaz R, MMWR Recomm Rep, 2008), the underlying malignancy might play a large role in the risk of VZV reactivation. There is little data comparing the proportion of VZV in multiple myeloma (MM) with other indolent B and T-cell lymphomas. The purpose of this study is to compare varicella infection in MM patients with chronic lymphocytic leukemia (CLL), cutaneous T-cell lymphoma (CTCL), and follicular lymphoma (FL). Given that VZV is a relatively common infection in patients with MM, we hypothesized that varicella reactivation in MM patients occurs at a higher rate than in patients with CLL, CTCL, or FL.Methods: A retrospective chart review of 3,765 patients was conducted. Patients were eligible if they had been diagnosed with 1 of 4 malignancies - MM (1,210), CLL (2,520), CTCL (434), or FL (809). Patients diagnosed with other malignancies i.e. mantle cell lymphoma were excluded, as were patients with multiple malignancies i.e. MM and FL. All patients had been seen at the Ohio State University Wexner Medical Center during their treatment. For each patient, information on age, gender, length of survival, age at diagnosis of hematologic malignancy, and proportion of patients with shingles was collected. Only patients who were diagnosed with shingles after hematologic cancer diagnosis were included as positive. Associations between malignancy type and development of shingles were analyzed by a chi-square test, and logistic regression was used to calculate odds ratios for shingles between MM and the other malignancies, controlling for age as a possible confounder. Median survival time was calculated in years using the Kaplan-Meier method, calculated as the time from cancer diagnosis to date of last contact if alive, or date of death if deceased. Seven patients were excluded from survival analysis due to having the same date of diagnosis as date of last contact. This study was approved by the cancer institutional review board.Results: Patient demographic information is found in Table 1. Of the 1,210 MM patients, 127 developed shingles after diagnosis (10.5%); of 2520 CLL patients, 326 were positive (12.9%); of 434 CTCL patients, 33 were positive (7.6%); of 809 FL patients, 78 were positive (9.6%). At a significance level of a=0.05, there was a significant association between cancer type and shingles (χ2=15.59, df=3, p-value=0.0014). Odds ratios comparing MM to each of the other lymphomas were not found to be significant. The median survival time in years was 8.8 for MM, 20.7 for CLL, 25.1 for CTCL, and 24.6 for FL (Figure 1).Conclusion: Patients with MM had the lowest median survival (8.8 years), and a significant association between cancer type and shingle incidence was found, with CTCL patients having the lowest incidence of shingles (7.6%) within the retrospective period. However, the odds ratios comparing MM to the other 3 lymphomas was not significant, showing that the MM patients did not have significantly higher rates of shingles as originally hypothesized. These results demonstrate the differences in viral infection incidence and disease course between hematologic malignancies, and that antiviral strategies more specialized to T and B cell lymphomas may be important in reducing the risk of viral infection. [Display omitted] DisclosuresHofmeister:Celgene: Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Research Funding; Takeda: Research Funding; Thrassos: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Bristol-Myers Squibb: Research Funding; Roche: Research Funding.

Immunomodulatory drugs increase the risk of serious infections in multiple myeloma patients: A meta-analysis using real-world data

Background: Immunomodulatory drugs like thalidomide, pomalidomide, and others are commonly used for the management of multiple myeloma. Epidemiological evidence showed variable findings. So, this meta-analysis is aimed to understand the association of immunomodulatory drug use and the risk of infections. Methods and materials: This meta-analysis was performed by adhering to the preferred reporting items for systematic review and meta-analysis guidelines. PubMed and Embase electronic databases were searched by two independent investigators. The study search period was from inception to September 2019. Only those observational studies qualified for inclusion which reported the association between any of the immunomodulatory drug's use and risk of serious infections. Study quality of included studies was assessed using the Newcastle-Ottawa scale. The primary outcome of this study was to investigate the rate of infections in multiple myeloma patients treated with immunomodulatory drugs. Secondary outcomes include risk based on different types of immunomodulatory drugs. All the analysis was done with RevMan software. Results: This meta-analysis was based on 3224 patients from all the included studies with a mean age range from 54 y to 75 y. Included studies reported infection incidence from 1.54% to 21.88%. Due to the significant heterogeneity, the random effect model was applied. Pooled incidence of infection due to immunomodulatory agents was 8.80% (95% CI: 6.90%–10.70%). The pooled incidence of serious infection among pomalidomide users with relapsed and refractory cases was 11.80% (95% CI: 6.50%–17.10%). Thalidomide user has a higher incidence in multiple myeloma patients who were on induction therapy 8.70% (95% CI: 5.40%–11.90%). Whereas the pooled incidence was lower in thalidomide user who was on maintenance therapy2.70% (95% CI: 0–6.70%). Conclusion: A higher risk of infections was observed in multiple myeloma patients receiving immunomodulatory therapy. Preventive management is essential for patients.

Levels of N-Terminal Pro-B-Type Natriuretic Peptide Relate to Risk of Infection in Multiple Myeloma Patients

Background Infections are a major complication in multiple myeloma (MM) patients and are associated with inferior outcomes. Thus there is a pressing need to predict risk of infection in MM patients. Methods Data from 110 MM patients were retrospectively analyzed. Patients were divided into high and low N-amino terminal fragment of the N-terminal pro-B-type natriuretic peptide (NT-proBNP) groups using the cut-off value 300ng/L at diagnosis. Results This study showed patients with high NT-proBNP had significantly higher beta-2-micorglobin (B2M), creatinine, lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group performance status (ECOG-PS) score, international staging system (ISS) score and lower estimated glomerular filtration rate (eGFR), hemoglobin, albumin than patients with low NT-proBNP. During the follow-up period, 46% presented at least one grade ≥3 infection. Patients with high NT-proBNP had high cumulative incidences of infections at the first 4 months and at the end of follow-up. Multivariate Cox regression analysis proved NT-proBNP to be an independent significant prognostic factor for grade ≥3 infections (relative ratio [RR] 2.190, 95% confidence interval [CI]: 1.126-4.261, P = 0.021). Conclusions This study revealed the potential of NT-proBNP for predicting risk of infection in MM patients. NT-proBNP may be applied as a criterion to identify patients with high risk of infection, who can benefit from prophylactic measures. Disclosures No relevant conflicts of interest to declare.

Genetic polymorphisms associated with clostridium difficile infection in multiple myeloma patients undergoing autologous stem cell transplantation.

8522 Background: CDI is the primary cause of infectious diarrhea in immunocompromised patients including those undergoing autologous stem cell transplant (SCT). Given the key role of gut microbiome and its interaction with host immune system, we investigated whether polymorphisms in innate immunity genes (identified through Ingenuity Pathway Analysis) were associated with CDI. Methods: We queried our database to identify MM patients who underwent an autologous SCT between April 2015-June 2019. Patients who had their buccal swabs collected through an IRB approved specimen collection protocol were included herein. Data were collected on age, conditioning regimen, CDI diagnosis, time from admission until CDI diagnosis, absolute neutrophil count (ANC) at time of CDI diagnosis, and antibiotic prophylaxis. Genomic DNA was extracted from buccal swabs and genotyped for 62 single nucleotide polymorphisms (SNPs) in ASPH , RLBP1L1, ATP7B, IL-8, FAK, TNFRSF14, CTH, TLR and IL-4. Univariate and multivariate logistic regression analyses were performed to assess association between CDI and presence of SNPs in these genes. Results: A total of 83 patients were identified (25 cases and 58 controls). Baseline characteristics were comparable between two groups. Median age was 67 years (range: 50-79). All patients received high dose melphalan as conditioning, and the same antibiotic prophylaxis during peri-transplant period. Median time from hospitalization until CDI diagnosis was 10 days (IQR:9 days), and median ANC was 0.7/mL (IQR:1.6/mL). Two SNPs (rs2227307 T &gt; G in IL-8 and rs2234167 G &gt; A in TNFRSF14) were significantly associated with CDI risk in both univariate and multivariate logistic regression analyses (Table). Conclusions: Our findings suggest that rs227307G (in IL-8) and rs2234167A (in TNFRSF14) alleles are potential risk factors for CDI after autologous SCT. Our findings, if validated in a larger cohort, would support genetic testing as a screening tool to identify patients who might benefit from prophylaxis against CDI. [Table: see text]

Association between diabetes mellitus, hypertension, hyperlipidemia, chronic viral hepatitis, and the risk of multiple myeloma: a case-control study

Abstract Objective This case-control study aimed to investigate whether diabetes mellitus (DM), hypertension, hyperlipidemia, and chronic viral hepatitis are risk factors for multiple myeloma (MM). Moreover, the clinical characteristics of MM patients with or without the abovementioned exposure factors were analyzed. Methods In total, 340 MM patients and 680 patients with benign diseases who were hospitalized from January 2012 to December 2017 were classified under the case group and control group, respectively. Data about medical history of DM, hypertension, hyperlipidemia and chronic viral hepatitis were collected by reviewing medical records. Univariate and multivariate analyses were conducted to compare the history of DM, hypertension, hyperlipidemia, and viral hepatitis between the two groups. Considering DM, hypertension, hyperlipidemia, and chronic viral hepatitis as exposure factors, clinical characteristics, such as renal function and presence of fungal and other types of infections, between the exposed and non-exposed groups were analyzed. Results No significant difference was observed in the prevalence of DM, hypertension, and hyperlipidemia between the case and control groups. MM patients had a higher prevalence of chronic viral hepatitis than those with benign diseases. No significant difference was observed in the prevalence of renal dysfunction, fungal infection, and non-fungal infections in MM patients with or without DM, hypertension, and hyperlipidemia. MM patients with chronic viral hepatitis had a significantly higher prevalence of non-fungal infections during hospitalization than those without. Conclusion No significant association was noted between MM and DM, hypertension, and hyperlipidemia. Chronic viral hepatitis is correlated to a significantly higher risk of MM, and MM patients with chronic viral hepatitis were more susceptible to non-fungal infections during hospitalization. Although a non-significant trend was observed in this study, we believe that DM and hypertension might be associated with a higher risk of MM. Thus, large-scale studies must be conducted to validate the results of the current study.

Risk, Outcomes, and Trends of Clostridium Difficile Infection in Multiple Myeloma Patients from a Nationwide Analysis.

Background: Patients hospitalized with hematologic malignancy are particularly vulnerable to infection. We sought to determine the risk of Clostridium difficile infection (CDI) in hospitalization with multiple myeloma (MM), as well as its outcomes and trends, using a nationally representative database.Methods: The Nationwide Inpatient Sample (NIS) from January 2010 to September 2015 was used for this study. We identified all patients aged 18 years or older with a diagnosis of MM using the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes. We identified trends in the annual rates of CDI in MM using negative binomial regressions with robust error variance. We conducted multivariate logistic regression to determine the incidence and the associated risk factors of CDI in MM and compared the outcomes between those with and without CDI using the propensity score method inverse probability weighting to adjust for baseline covariates.Results: In our cohort study of 114,249 MM patients, 45.96% were females and 54.04% were males. CDI was present in 3.1% of the MM patients. The number of CDI cases increased over the study period with an average rate of 3.27% per year. The mortality rate decreased over the same period with an average rate of 10% decrease per year. Hematopoietic stem cell transplantation (HSCT), neutropenia, inflammatory disease, atrial fibrillation (AF), and chronic kidney disease (CKD) were significant associated risk factors of CDI in MM patients. After adjusting for covariates, patients with CDI had a prolonged hospital stay, inpatient mortality, and significantly increased odds of acute kidney injury (AKI) and AKI requiring hemodialysis, along with higher healthcare resources utilization with significantly higher hospital costs.Conclusion: MM patients with CDI have significantly increased odds of inpatient mortality, AKI, and AKI requiring hemodialysis. They also have increased healthcare resource utilization compared with those without CDI. Despite the increased rate of the CDI over the years, the mortality rate is going down.

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

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. Using Danish registries (from 2005 to 2013), we analyzed all ICD-10 codes for infections within the first 6months of Multiple Myeloma diagnosis in 2557 patients. 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. Our study suggests that tumor burden and renal impairment are risk factors for pneumonia and sepsis in the early phase of Multiple Myeloma.