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We aimed to evaluate and compare the performance of multiple myeloma (MM) selection algorithms for use in Veterans Affairs (VA) research.Using the VA Corporate Data Warehouse (CDW), the VA Cancer Registry (VACR), and VA pharmacy data, we randomly selected 500 patients from 01/01/1999 to 06/01/2021 who had (1) either one MM diagnostic code OR were listed in the VACR as having MM AND (2) at least one MM treatment code. A team reviewed oncology notes for each veteran to annotate details regarding MM diagnosis and initial treatment within VA. We evaluated inter-annotator agreement and compared the performance of four published algorithms (two developed and validated external to VA data and two used in VA data).A total of 859 patients were reviewed to obtain 500 patients who were annotated as having MM and initiating MM treatment in VA. Agreement was high among annotators for all variables: MM diagnosis (98.3% agreement, Kappa = 0.93); initial treatment in VA (91.8% agreement; Kappa = 0.77); and initial treatment classification (87.6% agreement; Kappa = 0.86). VA Algorithms were more specific and had higher PPVs than non-VA algorithms for both MM diagnosis and initial treatment in VA. developed the "VA Recommended Algorithm," which had the highest PPV among all algorithms in identifying patients diagnosed with MM (PPV = 0.98, 95% CI = 0.95-0.99) and in identifying patients who initiated their MM treatment in VA (PPV = 0.93, 95% CI = 0.90-0.96).Our VA Recommended Algorithm optimizes sensitivity and PPV for cohort selection and treatment classification. This article is protected by copyright. All rights reserved.

With growing knowledge of multiple myeloma (MM) pathobiology and the introduction of novel therapies, risk stratification continues to evolve. Myeloid-derived suppressor cells and tumor-associated macrophages, derived from peripheral blood monocytes, support malignant plasma cell proliferation in the bone marrow. Since peripheral blood absolute monocyte count (AMC) is thought to could reflect the bone marrow microenvironment, we sought to evaluate the prognostic significance of AMC in MM. We retrospectively analyzed 10,822 patients with newly-diagnosed MM between 2000 and 2019 at Veteran's Administration hospitals. We obtained AMC closest to diagnosis and every 3 months thereafter up to 2.5 years. Patients were stratified into 4 groups: low, normal, elevated, and severely elevated AMC (AMC 0.2, 0.2 to0.8, 0.8-1.25 and1.25 x103/mm3, respectively). Abnormal AMC at diagnosis was observed in 25.3% of patients and was associated with inferior overall survival (OS). In patients with low, elevated, severely elevated, and normal AMC, At diagnorespectively, sis, median OS at diagnosis was 2.3, 2.7, 3.1, 3.6 years (p0.001), and at 2.5 years median OS at 2.5 years was 2.0, 2.6, 3.4, 3.9 years (p0.001) in patients with low, elevated, severely elevated, and normal AMC, respectively. Patients with normal AMC at diagnosis who developed an abnormal AMC1 year after diagnosis also had inferior OS relative to patients who maintained a normal AMC. Abnormal AMC was also associated with inferior OS independent of validated prognostic markers including the international staging system stage ISS Stage, and high lactate dehydrogenase LDH. Our findings provide novel clues for future prospective studies on the functional role of monocytes in multiple myeloma, which could be a readily available metric for risk stratification.

Perinatal HIV transmission has substantially decreased with combination antiretroviral regimens, but complications in children who are HIV-exposed but uninfected, such as microcephaly, warrant ongoing surveillance. We aimed to evaluate whether individual in utero antiretroviral exposures were associated with increased risk of microcephaly based on long-term follow-up of infants and children who are HIV-exposed but uninfected.We evaluated children aged younger than 18 years who were HIV-exposed but uninfected with at least one head circumference measurement while enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study at 22 clinical sites in the USA, including Puerto Rico. This prospective cohort study was done by the Pediatric HIV/AIDS Cohort Study network. Microcephaly was defined as having a head circumference Z score-2 according to the 2000 US Centers for Disease Control and Prevention growth charts for children 6-36 months old and according to Nellhaus standards (head circumference2nd percentile) after 36 months (SMARTT criteria); an alternate definition for microcephaly was based on applying Nellhaus standards across all ages (Nellhaus criteria). Modified Poisson regression models were fit to obtain relative risks (RRs) for associations between in utero antiretroviral exposure and microcephaly status, adjusted for potential confounders. Neurodevelopmental functioning was compared in children who are HIV-exposed but uninfected with or without microcephaly.Between March 21, 2007, and Aug 1, 2017, 3055 participants enrolled in SMARTT had at least one head circumference measurement. The cumulative incidence of microcephaly over a median of 5·1 years of follow-up (IQR 3·0-7·2) was 159 (5·2%, 95% CI 4·4-6·1) by Nellhaus criteria and 70 (2·3%, 1·8-2·9) by SMARTT criteria. In adjusted models, in utero exposure to efavirenz (4·7% exposed) was associated with increased risk of microcephaly by both Nellhaus standards (adjusted RR 2·02, 95% CI 1·16-3·51) and SMARTT criteria (2·56, 1·22-5·37). These associations were more pronounced in children exposed to combination regimens of efavirenz that included zidovudine plus lamivudine than those including tenofovir plus emtricitabine. Protective associations were observed for darunavir exposure (adjusted RR 0·50, 95% CI 0·24-1·00). Children who are HIV-exposed but uninfected with microcephaly had lower mean scores on neurodevelopmental assessments at age 1 and 5 years and a higher prevalence of neurodevelopmental impairment than those without microcephaly.These findings support consideration of alternatives to efavirenz as part of first-line antiretroviral therapy for pregnant women.Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Antiretroviral (ARV) adherence is critical in monitoring disease response in youth with perinatally-acquired HIV (PHIV). We used pharmacy refill (PR) information for PHIV youth from the PHACS Memory Sub-study to calculate medication availability over 2, 4, and 6 months. PR, a proxy of adherence, was compared with self-reported 7-day adherence in predicting suppressed viral load (SVL

Electronic frailty indices based on data from administrative claims and electronic health records can be used to estimate frailty in large populations of older adults with cancer where direct frailty measures are lacking. The objective of this study was to use the electronic Veterans Affairs Frailty Index (VA-FI-10)—developed and validated to measure frailty in the national United States (US) VA Healthcare System—to estimate the prevalence and impact of frailty in older US veterans newly treated for multiple myeloma (MM) with contemporary therapies. We designed a retrospective cohort study of 4924 transplant-ineligible veterans aged ≥ 65 years initiating MM therapy within VA from 2004 to 2017. Initial MM therapy was measured using inpatient and outpatient treatment codes from pharmacy data in the VA Corporate Data Warehouse. In total, 3477 veterans (70.6%) were classified as frail (VA-FI-10 &gt, 0.2), with 1510 (30.7%) mildly frail (VA-FI-10 &gt, 0.2–0.3), 1105 (22.4%) moderately frail (VA-FI-10 &gt, 0.3–0.4), and 862 (17.5%) severely frail (VA-FI-10 &gt, 0.4). Survival and time to hospitalization decreased with increasing VA-FI-10 severity (log-rank p-value &lt, 0.001), the VA-FI-10 predicted mortality and hospitalizations independently of age, sociodemographic variables, and measures of disease risk. Varying data sources and assessment periods reclassified frailty severity for a substantial portion of veterans but did not substantially affect VA-FI-10’s association with mortality. Our study supports use of the VA-FI-10 in future research involving older veterans with MM and provides insights into its potential use in identifying frailty in clinical practice.

Background The Veterans Affairs Frailty Index (VA-FI) is an electronic frailty index developed to measure frailty using administrative claims and electronic health records data in Veterans. An update to ICD-10 coding is needed to enable contemporary measurement of frailty. Method International Classification of Diseases, ninth revision (ICD-9) codes from the original VA-FI were mapped to ICD-10 first using the Centers for Medicaid and Medicare Services (CMS) General Equivalence Mappings. The resulting ICD-10 codes were reviewed by 2 geriatricians. Using a national cohort of Veterans aged 65 years and older, the prevalence of deficits contributing to the VA-FI and associations between the VA-FI and mortality over years 2012–2018 were examined. Results The updated VA-FI-10 includes 6422 codes representing 31 health deficits. Annual cohorts defined on October 1 of each year included 2 266 191 to 2 428 115 Veterans, for which the mean age was 76 years, 97%–98% were male, 78%–79% were White, and the mean VA-FI was 0.20–0.22. The VA-FI-10 deficits showed stability before and after the transition to ICD-10 in 2015, and maintained strong associations with mortality. Patients classified as frail (VA-FI > 0.2) consistently had a hazard of death more than 2 times higher than nonfrail patients (VA-FI ≤ 0.1). Distributions of frailty and associations with mortality varied with and without linkage to CMS data and with different assessment periods for capturing deficits. Conclusions The updated VA-FI-10 maintains content validity, stability, and predictive validity for mortality in a contemporary cohort of Veterans aged 65 years and older, and may be applied to ICD-9 and ICD-10 claims data to measure frailty.

Background Traditional count-based measures of comorbidity are unlikely to capture the complexity of multiple chronic conditions (multimorbidity) in older adults with cancer. We aimed to define patterns of multimorbidity and their impact in older United States veterans with multiple myeloma (MM). Methods We measured 66 chronic conditions in 5076 veterans aged 65 years and older newly treated for MM in the national Veterans Affairs health-care system from 2004 to 2017. Latent class analysis was used to identify patterns of multimorbidity among these conditions. These patterns were then assessed for their association with overall survival, our primary outcome. Secondary outcomes included emergency department visits and hospitalizations. Results Five patterns of multimorbidity emerged from the latent class analysis, and survival varied across these patterns (log-rank 2-sided P Conclusions Our findings demonstrate the need to move beyond count-based measures of comorbidity and consider cancer in the context of multiple chronic conditions.

Background Emerging data suggest variability in susceptibility and outcome to coronavirus disease 2019 (COVID-19) infection. Identifying risk factors associated with infection and outcomes in cancer patients is necessary to develop healthcare recommendations. Methods We analyzed electronic health records of the US Veterans Affairs Healthcare System and assessed the prevalence of COVID-19 infection in cancer patients. We evaluated the proportion of cancer patients tested for COVID-19 who were positive, as well as outcome attributable to COVID-19, and stratified by clinical characteristics including demographics, comorbidities, cancer treatment, and cancer type. All statistical tests are 2-sided. Results Of 22 914 cancer patients tested for COVID-19, 1794 (7.8%) were positive. The prevalence of COVID-19 was similar across age. Higher prevalence was observed in African American (15.0%) compared with White (5.5%; P < .001) and in patients with hematologic malignancy compared with those with solid tumors (10.9% vs 7.8%; P < .001). Conversely, prevalence was lower in current smokers and patients who recently received cancer therapy ( Conclusion Preexistence of cancer affects both susceptibility to COVID-19 infection and eventual outcome. The overall COVID-19–attributable mortality in cancer patients is affected by age, comorbidity, and specific cancer types; however, race or recent treatment including immunotherapy do not impact outcome.

BackgroundEmerging data suggest variability in susceptibility and outcome to Covid-19 infection. Identifying the risk-factors associated with infection and outcomes in cancer patients is necessary to develop healthcare recommendations.MethodsWe analyzed electronic health records of the US National Veterans Administration healthcare system and assessed the prevalence of Covid-19 infection in cancer patients. We evaluated the proportion of cancer patients tested for Covid-19 and their confirmed positivity, with clinical characteristics, and outcome, and stratified by demographics, comorbidities, cancer treatment and cancer type.ResultsOf 22914 cancer patients tested for Covid-19, 1794 (7.8%) were positive. The prevalence of Covid-19 was similar across all ages. Higher prevalence was observed in African-American (AA) (15%) compared to white (5.5%; PConclusionPre-existence of cancer affects both susceptibility to Covid-19 infection and eventual outcome. The overall Covid-19 attributable mortality in cancer patients is affected by age, co-morbidity and specific cancer types, however, race or recent treatment including immunotherapy does not impact outcome.FundingsVA Office of Research and Development and National Institutes of Health.

Objective To evaluate whether there is an increased risk of neurologic diagnoses in children who are HIV-exposed but uninfected (CHEU) exposed in utero to specific antiretroviral medications. Design Prospective cohort study of CHEU enrolled from 2007 to 2017. Methods We evaluated children for neurologic case status, including microcephaly, febrile seizures, seizure disorders, ophthalmologic disorders, and other neurologic disorders. Adjusted relative risks (aRRs) were estimated for the association between in-utero antiretroviral exposure and neurologic case using log-binomial regression, accounting for potential confounders. Sensitivity analyses were conducted to evaluate robustness of findings. Results Among 3747 eligible CHEU, 231 (6.2%) met neurologic case criteria (95% CI 5.4--7%). Most eligible children (86%) were exposed in utero to combination antiretroviral regimens. In adjusted models, children exposed to efavirenz at any time during pregnancy had higher risk of neurologic case status (aRR = 1.53, 95% CI 0.94--2.51). This association was stronger when comparing efavirenz exposure at conception to no exposure during pregnancy (aRR = 1.92, 95% CI 1.09--3.36) and considering follow-up and case diagnosis only through age 2 (aRR = 2.14, 95% CI 1.11--4.12). Children exposed to didanosine at conception and during the first trimester had increased risk of neurologic case status (aRR = 2.28, 95% CI 1.07--4.87 and aRR = 2.02, 95% CI 1.01--4.04, respectively), compared with didanosine-unexposed children. Children with dolutegravir exposure had some suggestion of increased risk of neurologic case (aRR = 2.43, 95% CI 0.75--7.84), which was observed consistently across several sensitivity analyses. Conclusion Efavirenz and didanosine exposure during pregnancy were associated with higher risk of neurologic abnormalities in CHEU, and dolutegravir exposure showed some suggestive associations, which warrant further monitoring.

Introduction : Multiple myeloma (MM) is a heterogeneous disease with diverse clinical outcomes. Although survival in MM has improved, high risk patients still experience early relapses and shorter survival. Current methods for risk stratification in MM are useful at diagnosis but need to be refined as our knowledge of disease pathobiology evolves. Tumor-associated macrophages, derived from peripheral blood monocytes, support malignant plasma cell proliferation in the bone marrow (BM) microenvironment. Since peripheral blood absolute monocyte count (AMC) could reflect the BM microenvironment, we evaluated the prognostic significance of AMC in MM at diagnosis and during the disease course. Methods: We used the nationwide Veterans Affairs electronic health records to include treatment-naïve MM patients diagnosed between 2000 and 2019 without concomitant aplastic anemia, myelodysplastic syndrome, myeloproliferative neoplasm, and acute or chronic leukemia. We obtained AMC (x10 3) closest to and within 90 days from diagnosis and every 3 months thereafter up to 2.5 years. Patients were stratified into 4 AMC groups: low (AMC < 0.2), normal (AMC 0.2 to < 0.8), elevated (AMC 0.8-1.25), and severely elevated (AMC > 1.25). Our selection criteria excluded any treatment-related change in AMC. Overall survival (OS) was evaluated using the Kaplan-Meier estimator and logrank tests. Cox proportional hazard models were used for multivariable analysis. Results: We analyzed 10,822 patients, median age 70 years (interquartile range [IQR] 63-77) with a median follow up of 2.9 years (IQR 1.3-5.3). At diagnosis, 25.3% of patients (2737 of 10,822) presented with abnormal AMC; with 5% having low, 16.7% elevated, and 3.6% severely elevated AMC. Patients with monocytosis (elevated or severely elevated AMC) were younger and more likely to have higher median levels of beta-2-microglobulin and lactate dehydrogenase (LDH) and lower median levels of albumin (p < 0.001) than those without monocytosis. Abnormal AMC at diagnosis significantly impacted overall survival (p < 0.001) . Patients with low, severely elevated, elevated, and normal AMC at diagnosis had median OS of 2.3, 2.7, 3.1, and 3.5 years (p < 0.001), respectively (Figure 1). Persistent AMC abnormality also impacted outcomes. Abnormal AMC > 1 year after diagnosis was also associated with inferior OS (median OS at 2.5 years - 2.0, 2.6, 3.4, and 3.9 years in patients with low, severely elevated, elevated, and normal AMC respectively [p < 0.001]) (Figure 2). If patients with normal AMC at diagnosis developed an abnormal AMC > 1 year after diagnosis, median OS was reduced relative to if they maintained normal AMC (Figure 3). Notably, median OS improved across all AMC groups in patients with MM diagnosed after 2012 when modern therapies became standard of care. However, the adverse survival impact of low, elevated, or severely elevated AMC persisted in all time periods. After adjusting for known prognostic factors (age, ISS Stage, LDH), multivariable analysis showed similar results, with a significant association of OS with AMC at diagnosis (Figure 4) and AMC measured up to 2.5 years after diagnosis. Hazard Ratios (HR) at diagnosis were 1.28 (95% confidence interval [CI] 1.16-1.41; p < 0.001), 1.10 (95%CI 1.04-1.17; p = 0.002), and 1.19 (95%CI 1.06-1.34; p = 0.004), and HRs at 2.5 years after diagnosis were 1.53 (95%CI 1.22-1.93; p < 0.001), 1.11 (95%CI 1.00-1.23; p = 0.043, 1.58 (95%CI 1.22-2.04; p < 0.001) for low, elevated and severely elevated AMC, respectively. Conclusion : Abnormal AMC is frequently observed in MM and is a powerful, easily attainable prognostic biomarker. Abnormal AMC at diagnosis or follow up of MM is significantly associated with inferior OS, independent of established prognostic factors. Survival was also inferior for patients who had normal AMC at diagnosis but then developed abnormal AMC, possibly suggesting changes in the BM microenvironment over time. Given the improved prognosis of patients with severely elevated AMC in patients diagnosed with MM after 2012, our data potentially highlights the mechanism of action of novel treatments interacting with the tumor microenvironment. Whether these findings reflect disease biology, a consequence of disease progression, or both warrants further in vitro, prospective studies. Overall, AMC is a readily available metric that could be included in the risk stratification of MM at diagnosis and beyond. Figure 1 Figure 1. Disclosures Munshi: Takeda: Consultancy; Bristol-Myers Squibb: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Legend: Consultancy; Novartis: Consultancy; Adaptive Biotechnology: Consultancy; Pfizer: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Abbvie: Consultancy.

Youth with perinatal HIV infection (PHIV) are at increased risk for neurocognitive impairment. Prospective memory (PM) is a complex neurocognitive function that has been shown to be impaired in adults with HIV disease and independently associated with poorer daily living skills, including medication non-adherence. The current study sought to determine the presence and extent of PM deficits in youth with PHIV. Participants included 173 youth with PHIV and 85 youth HIV-exposed but uninfected (PHEU), mean age 14.1 years, 75% black, 18% Hispanic. Among youth with PHIV, 26% had a past AIDS-defining condition (Centers for Disease Control and Prevention [CDC], Class C), 74% did not (non-C). Adjusted generalized estimating equation models were used to compare groups (PHIV/C, PHIV/non-C, and PHEU) on the Naturalistic Event-Based Prospective Memory Test (NEPT) and the Prospective Memory Assessment for Children & Youth (PROMACY). Secondarily, subgroups defined by HIV serostatus and global neurocognitive impairment (NCI) were compared (PHIV/NCI, PHIV/non-NCI, PHEU). PHIV/C had significantly lower NEPT scores than PHEU, with decreases of 40% in mean scores, but did not differ from PHIV/non-C. PHIV/NCI had 11–32% lower PROMACY scores and 33% lower NEPT scores compared to PHIV/non-NCI (all p

Introduction : Multiple myeloma (MM) is an incurable hematologic malignancy caused by the neoplastic proliferation of plasma cells within the bone marrow. The tumor microenvironment within the bone marrow consists of a diverse array of immune cells which regulate MM cell proliferation and survival. Specifically, tumor-associated macrophages (TAMs) derived from peripheral blood monocytes migrate to the bone marrow where they support MM cell growth and promote resistance to apoptosis. Several studies suggest that the amount of bone marrow TAMs directly correlates with disease activity and worse clinical outcomes in MM. Considering that peripheral blood absolute monocyte count (AMC) could reflect the burden of bone marrow TAMs, we sought to determine the prognostic significance of AMCs at diagnosis of MM. Methods: Using the integrated nationwide VA electronic health records and VA Corporate Data Warehouse, patients were identified by International Classification of Diseases (ICD) codes for MM. Patients were required to have at least 3 visits with an MM ICD code on separate days, have received at least one MM drug with the exception of corticosteroids after the date of diagnosis and have 2 or more absolute monocyte counts measured by automated or manual differential at separate visits within 18 months before and 7 days after MM diagnosis. We further confirmed the date of diagnosis using the VA Cancer Registry. We excluded patients with aplastic anemia, myelodysplastic syndrome, chronic myelomonocytic leukemia and other myeloproliferative neoplasms. In this cohort, monocytosis was defined based on the institution's cut-off as a sustained absolute increase in monocyte count of 0.8 (800/mm3) or greater with extreme monocytosis being greater than 1.25 (1250/mm3). Patients were stratified into three groups according to AMC at diagnosis, namely AMC 1.25. To avoid extreme values significantly affecting the analysis, the Kruskal-Wallis test was used to compare continuous variables between the groups. Chi-squared tests were used to compare categorical variables. Hazard estimates for the prognostic analysis were obtained via adjusted Cox proportional hazard models. Overall survival was estimated using the Kaplan-Meier method and log-rank tests were used to compare the survival of each group. Results: A total of 5,265 patients with MM were included in the final analysis with a median follow up of 2.9 years (range 1.3 - 5.2). At diagnosis of MM, 39.3% of patients presented with monocytosis. Patients with monocytosis were younger and more likely to have abnormal levels of prognostic markers known to be associated with increased tumor burden and worse outcomes in MM. Notably, patients with monocytosis had higher median levels of β2-microglobulin and lactate dehydrogenase (p 1.25 groups respectively (p 1.25 HR of 1.312, p Conclusion : The results of our study suggest that an elevated absolute monocyte count at MM diagnosis is associated with worse overall survival independent of known poor prognostic factors. The role of peripheral blood monocyte count as a surrogate biomarker for the state of the bone marrow microenvironment in MM warrants further in vitro, prospective studies. Disclosures Munshi: AbbVie: Consultancy; Amgen: Consultancy; Legend: Consultancy; Adaptive: Consultancy; Janssen: Consultancy; C4: Current equity holder in private company; OncoPep: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Karyopharm: Consultancy; Takeda: Consultancy; BMS: Consultancy.

10507 Background: In the recent decade, novel therapies have led to significant improvements in overall survival (OS) in symptomatic multiple myeloma (MM). With this increase in OS, there is an increase in the incidence of second primary malignancies (SPM) in patients with MM. This is related to multiple factors; we hypothesize that racial disparities also play a role. There is a paucity of studies with large, high quality datasets evaluating racial disparities in SPMs in MM. Our goal is to explore patterns of incidence of SPMs in US Veterans with MM, focusing on racial disparities. Methods: We conducted a retrospective cohort study based on electronic health record (EHR) and cancer registry data recorded in the VA’s Corporate Data Warehouse (CDW) between January 1, 1999 and January 1, 2018. We compared incidence of SPMs (defined as malignancies occurring after the diagnosis and treatment initiation of MM) using the standardized incidence rate ratio (IRR). Univariate and multivariable analyses were performed, using a Cox model adjusting for age, race, gender, treatment era, smoking status, and stage at MM diagnosis. Results: There were 8467 Veterans (97.4% male) with MM identified with self-reported race: White, 5029 (59.4%); AA, 2178 (25.7%); and other or unknown, 1260 (14.9%). At 7.5 years of follow up, 430 (5.1%) MM patients developed SPM while 8037 did not. 982 had received HSCT (Hematopoietic Stem cell transplant) of whom 65 (6.62%), a significantly higher proportion developed SPM versus those without HSCT (n = 7485) of whom 365 (4.87%) developed SPM (p = 0.024). Among those Veterans who had SPM 380 (88.3%) had solid tumors, 50 (11.6 %) had hematological malignancies. Of 88.3% with solid SPM the distribution was: prostate cancer, 113 (29.7%); digestive tract cancers, 63 (16.6%); lung cancer, 55 (14.4%); and GU (bladder/renal/testicular), 48(12.6%). The cumulative incidence of developing SPM increased steadily over time for the duration of this study period of 7.5 years from diagnosis. The median age of diagnosis for Whites was 68.2 years and for AA was 64.3 years, (p < 0.001) demonstrating that MM occurred earlier in AA. The hazard ratio for AA versus whites to develop SPMs was 1.21 (0.975-1.505) (p = 0.0823). However, the risk of prostate cancer was significantly higher in AA with an adjusted hazard ratio of 1.81 (1.196-2.739) (p = 0.005). No racial disparities were observed in the incidence of other types of SPMs. Conclusions: Our study suggests that the risk of SPMs does not plateau over a patient’s lifetime. HSCT was found to be an independent predictor of SPM, while smoking and agent orange were not. Our cohort is one of the largest groups of AA with MM in published literature. AA did not have a higher incidence of SPMs overall; but had a significantly higher incidence of prostate cancer than whites. We hope to develop an individualized predictive model for SPM in patients with MM.

BACKGROUND Perinatally acquired HIV (PHIV) confers risk for neurocognitive impairment, which potentially affects school performance and functional independence of infected children. In this study, we examined the associations of 2 key neurocognitive domains, memory and executive function (EF), with academic and adaptive skills among youth with PHIV and perinatally HIV-exposed but uninfected (PHEU) youth. METHODS Participants ages 9 to

BACKGROUND Executive functions (EFs) are critical for management of life activities, but few studies have evaluated EFs in children and adolescents with perinatally acquired HIV (PHIV), who are at risk for problems in academics, behavior, and medication adherence. We compared EFs in youth with PHIV and in perinatally HIV-exposed but uninfected (PHEU) youth. METHODS Four Delis-Kaplan Executive Function System (D-KEFS) subtests were administered to 173 youth with PHIV and 85 PHEU youth, aged 9 to

OBJECTIVE To evaluate the safety of in-utero antiretroviral exposure in children born to mothers with HIV, using a trigger-based design. DESIGN The Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites to evaluate safety of in-utero antiretroviral drug exposure in HIV-uninfected children born to HIV-infected mothers. Children meeting predefined clinical or laboratory thresholds have more intensive evaluations to determine whether they meet criteria for adverse events. METHODS Adverse event "cases" were defined for the following domains: growth, hearing, language, neurology, neurodevelopment, metabolic, hematologic/clinical chemistry and blood lactate. We used adjusted log-binomial models to calculate relative risks (RR) of case status overall and within individual domains for various antiretroviral exposures during pregnancy. RESULTS Among 2680 youth enrolled between 2007 and 2012 (48% female, 66% black, 33% Hispanic), 48% met a trigger and 25% were defined as a case in at least one domain. Language (13.2%) and metabolic (11.4%) cases were most common. After adjustment for birth cohort and other factors, there was no association of any antiretroviral regimen, drug class, or individual drug with meeting overall case criteria (case in any domain). Within individual domains, zidovudine (74% exposed) was associated with increased risk of metabolic case [RR = 1.69, 95%confidence interval (CI) 1.08-2.64] and didanosine plus stavudine (

BACKGROUND Little is known regarding effects of perinatally acquired HIV infection (PHIV) on longitudinal change in memory and executive functioning (EF) during adolescence despite the importance of these skills for independence in adulthood. METHODS PHIV (n = 144) and perinatally HIV-exposed uninfected youth (PHEU, n = 79), ages 12-17, completed standardized tests of memory and EF at baseline and 2 years later. Changes from baseline for each memory and EF outcome were compared between PHEU and PHIV youth with (PHIV/C, n = 39) and without (PHIV/non-C, n = 105) history of CDC class C (AIDS-defining) diagnoses. Among PHIV youth, associations of baseline and past disease severity with memory and EF performance at follow-up were evaluated using adjusted linear regression models. RESULTS Participants were primarily black (79%); 16% were Hispanic; 55% were female. Mean memory and EF scores at follow-up generally fell in the low-average to average range. Pairwise comparison of adjusted mean change from baseline to follow-up revealed significantly greater change for PHIV/non-C compared with PHEU youth in only one verbal recognition task, with a difference in mean changes for PHIV/non-C versus PHEU of -0.99 (95% CI: -1.80 to -0.19; P = 0.02). Among youth with PHIV, better immunologic status at baseline was positively associated with follow-up measures of verbal recall and recognition and cognitive inhibition/flexibility. Past AIDS-defining diagnoses and higher peak viral load were associated with lower performance across multiple EF tasks at follow-up. CONCLUSIONS Youth with PHIV demonstrated stable memory and EF during a 2-year period of adolescence, allowing cautious optimism regarding long-term outcomes.

Background: In the recent decade, there have been dramatic improvements in multiple myeloma (MM) survival, owing principally to developments in therapeutic options. However, these developments have also raised concerns as to increase in second primary malignancies (SPMs) attributable to these therapies. For example, a Swedish study showed an increased risk of developing acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) in MM patients (11.51 fold), along with 1.19-fold increased risk of non-hematologic malignancies. However, it is presently unclear whether this increase is related to therapy or other factors such as host, environment or behavioral patterns. Here, we study incidence of SPM and association with demographics, exposure, and therapy in a large population in the US Veterans Affairs (VA) healthcare system. Methods: We used the VA's nationwide Corporate Data Warehouse to identify patients diagnosed with MM from 1999 to 2017, as well as their age, race, therapy at induction, stem-cell transplant status, and exposure status. For each patient, we identified the first SPM after MM treatment initiation using the VA Central Cancer Registry. We excluded patients who had records of malignancies prior to MM treatment initiation. Results: We identified 14,261 patients meeting the inclusion criteria, of whom 552 (3.9%) had SPMs, consistent with prior literature. Median age at MM diagnosis was 69.22 years overall (95% CI 51.98-84.76), 66.7 years (52.03-83.86) for those with SPM, and 69.32 years (51.99-) for those without SPM. Median age at diagnosis of SPM was 70.2 years (55.43-86.75). Median time from MM treatment initiation to SPM was 2.38 years (0.09-9.37). Of the 552 observed SPMs, 69 (12.4%) were hematologic (25 MDS, 19 lymphoma, 15 acute leukemia, 6 chronic leukemia, 4 MPN) while 84.5% (466) were oncologic. Prostate cancer was the most common SPM (n=125, 22.6%). We did not observe statistically significant differences in incidence of SPM by smoking status (4.1% among current/former smokers vs 3.7% among never smokers; P=0.347), or Agent Orange exposure (4.2% among those exposed vs 3.8% among those not exposed; P=0.476). We also examined the relationship of common treatments to SPM. SPM is more common among those exposed to lenalidomide (4.3% vs 3.4%, p=0.003), bortezomib (4.8 vs 3.3%, p Conclusion: In comparison to data from the VA Central Cancer Registry on cancer incidence at the VA in general, the incidence of SPM (3.9%) that we report among MM patients is substantially higher than the overall incidence of malignancy in the VA (0.78%). Moreover, we find that common risk factors for developing malignancy, including smoking status and exposure to Agent Orange, are not significantly associated with developing SPM after MM diagnosis. In contrast, we find that therapy utilization, particularly transplant, is associated with significant increases in susceptibility to SPM. Better understanding of these risk factors is needed to appropriately assess the tradeoff of decreased myeloma-related mortality, but potentially increased risk of secondary malignancies with common myeloma therapy options. Disclosures Yellapragada: Novartis: Employment, Other: Spouse Employment ; Celgene: Research Funding; BMS: Research Funding; Takeda: Research Funding. Munshi:Abbvie: Consultancy; Adaptive: Consultancy; Adaptive: Consultancy; Amgen: Consultancy; Amgen: Consultancy; Celgene: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Takeda: Consultancy; Oncopep: Consultancy; Oncopep: Consultancy; Abbvie: Consultancy.

The Pediatric HIV/AIDS Cohort Study’s Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites between 2007 and 2011 that was designed to evaluate the safety of in utero antiretroviral drug exposure in children not infected with human immunodeficiency virus who were born to mothers who were infected. This ongoing study uses a “trigger-based” design; that is, initial assessments are conducted on all children, and only those meeting certain thresholds or “triggers” undergo more intensive evaluations to determine whether they have had an adverse event (AE). The authors present the estimated rates of AEs for each domain of interest in the Surveillance Monitoring of ART Toxicities Study. They also evaluated the efficiency of this trigger-based design for estimating AE rates and for testing associations between in utero exposures to antiretroviral drugs and AEs. The authors demonstrate that estimated AE rates from the trigger-based design are unbiased after correction for the sensitivity of the trigger for identifying AEs. Even without correcting for bias based on trigger sensitivity, the trigger approach is generally more efficient for estimating AE rates than is evaluating a random sample of the same size. Minor losses in efficiency when comparing AE rates between persons exposed and unexposed in utero to particular antiretroviral drugs or drug classes were observed under most scenarios.

Importance Most studies examining the association of prenatal antiretroviral (ARV) exposures with congenital anomalies (CAs) in children born to human immunodeficiency virus (HIV)–infected women have been reassuring, but some evidence suggests an increased risk with specific ARV agents. Objective To evaluate the association of in utero ARV exposures with CAs in HIV-exposed uninfected children. Design, Setting, and Participants Prospective cohort study design. The Pediatric HIV/AIDS Cohort Study’s Surveillance Monitoring of ART Toxicities (SMARTT) Study was performed at 22 US medical centers among 2580 HIV-exposed uninfected children enrolled in the SMARTT Study between March 23, 2007, and June 18, 2012. Exposures First-trimester exposure to any ARV and to specific ARV medications. Main Outcomes and Measures The primary end point was a CA based on physician review of infant physical examinations according to the Antiretroviral Pregnancy Registry modification of the Metropolitan Atlanta Congenital Defects Program. Rates of CAs were estimated overall and by birth year. Logistic regression models were used to evaluate the association of CAs with first-trimester ARV exposures, adjusting for demographic and maternal characteristics. Results Congenital anomalies occurred in 175 of 2580 children, yielding a prevalence of 6.78% (95% CI, 5.85%-7.82%); 242 major CAs were confirmed, including 72 musculoskeletal and 55 cardiovascular CAs. The prevalence of CAs increased significantly among successive birth cohorts (3.8% for children born before 2002 and up to 8.3% for those born 2008-2010). In adjusted models, no association of first-trimester exposures with CAs was found for any ARV, for combination ARV regimens, or for any drug class. No individual ARV in the reverse transcriptase inhibitor drug classes was associated with an increased risk of CAs. Among protease inhibitors, higher odds of CAs were observed for atazanavir sulfate (adjusted odds ratio [aOR], 1.95; 95% CI, 1.24-3.05) and for ritonavir used as a booster (aOR, 1.56; 95% CI, 1.11-2.20). With first-trimester atazanavir exposure, risks were highest for skin (aOR, 5.23) and musculoskeletal (aOR, 2.55) CAs. Conclusions and Relevance Few individual ARVs and no drug classes were associated with an increased risk of CAs in HIV-exposed infants after adjustment for calendar year and maternal characteristics. While the overall risk remained low, a relative increase was observed in successive years and with atazanavir exposure. Given the low absolute CA risk, the benefits of recommended ARV therapy use during pregnancy still outweigh such risks, although further studies are warranted.

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