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The clinical course of patients with recently diagnosed early stage chronic lymphocytic leukemia (CLL) is highly variable. We examined the relationship between CLL-cell birth rate and treatment-free survival (TFS) in 97 patients with recently diagnosed, Rai stage 0-II CLL in a blinded, prospective study, using in vivo 2H2O labeling. Birth rates ranged from 0.07 to 1.31% new cells per day. With median follow-up of 4.0 years, 33 subjects (34%) required treatment by NCI criteria. High-birth rate was observed in 44% of subjects and was significantly associated with shorter TFS, unmutated IGHV status and expression of ZAP70 and of CD38. In multivariable modeling considering age, gender, Rai stage, expression of ZAP70 or CD38, IGHV mutation status and FISH cytogenetics, only CLL-cell birth rate and IGHV mutation status met criteria for inclusion. Hazard ratios were 3.51 (P=0.002) for high-birth rate and 4.93 (P

Background: Genetic mutations drive the pathogenesis of the myelodysplastic syndrome (MDS) and are closely associated with clinical phenotype. Therefore, genetic mutations may predict clinical outcomes after allogeneic hematopoietic stem-cell transplantation.Methods: We performed targeted mutational analysis on samples obtained before transplantation from 1514 patients with MDS who were enrolled in the Center for International Blood and Marrow Transplant Research Repository between 2005 and 2014. We evaluated the association of mutations with transplantation outcomes, including overall survival, relapse, and death without relapse.Results: TP53 mutations were present in 19% of the patients and were associated with shorter survival and a shorter time to relapse than was the absence of TP53 mutations, after adjustment for significant clinical variables (P<0.001 for both comparisons). Among patients 40 years of age or older who did not have TP53 mutations, the presence of RAS pathway mutations was associated with shorter survival than was the absence of RAS pathway mutations (P=0.004), owing to a high risk of relapse, and the presence of JAK2 mutations was associated with shorter survival than was the absence of JAK2 mutations (P=0.001), owing to a high risk of death without relapse. The adverse prognostic effect of TP53 mutations was similar in patients who received reduced-intensity conditioning regimens and those who received myeloablative conditioning regimens. By contrast, the adverse effect of RAS pathway mutations on the risk of relapse, as compared with the absence of RAS pathway mutations, was evident only with reduced-intensity conditioning (P<0.001). In young adults, 4% of the patients had compound heterozygous mutations in the Shwachman-Diamond syndrome-associated SBDS gene with concurrent TP53 mutations and a poor prognosis. Mutations in the p53 regulator PPM1D were more common among patients with therapy-related MDS than those with primary MDS (15% vs. 3%, P<0.001).Conclusions: Genetic profiling revealed that molecular subgroups of patients undergoing allogeneic hematopoietic stem-cell transplantation for MDS may inform prognostic stratification and the selection of conditioning regimen. (Funded by the Edward P. Evans Foundation and others.). [ABSTRACT FROM AUTHOR]

Several vaccine strategies have been tested for the treatment of follicular lymphoma; however, none have proven successful. In a phase I dose-escalation protocol, we developed a vaccine consisting of lethally irradiated whole lymphoma cells admixed with K562 cells that constitutively secreted granulocyte-macrophage colony-stimulating factor (GM-K562)(ClinicalTrials.gov identifier: NCT00487305). Patients with grade 1, 2, or 3 A follicular lymphoma were divided into 2 study tiers based on prior treatment and received a maximum of 6 vaccines. Vaccines contained dose levels of 5 × 10 6 or 1 × 10 7 GM-K562 cells admixed with autologous tumor cells at doses ranging from 1 × 10 5 to 5 × 10 7 .Correlative studies did not demonstrate a significant immune response as assessed by delayed-type hypersensitivity reactions, B and T cell subsets, and natural killer cell subsets. Future vaccine studies should focus on identifying lymphoma-specific immunogenic proteins and modifying the vaccine immune adjuvant.

STOP-CA was a multicenter, double-blind, randomized, placebo-controlled trial comparing atorvastatin to placebo in treatment-naïve lymphoma patients receiving anthracycline-based chemotherapy. We performed a preplanned subgroup to analyze the impact of atorvastatin on efficacy in patients with diffuse large B-cell lymphoma (DLBCL). Patients received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at standard doses for six 21-day cycles and were randomly assigned to receive atorvastatin 40 mg daily ( n  = 55) or placebo ( n  = 47) for 12 months. The complete response (CR) rate was numerically higher in the atorvastatin arm (95% [52/55] vs. 85% [40/47], p  = .18), but this was not statistically significant. Adverse event rates were similar between the atorvastatin and placebo arms. In summary, atorvastatin did not result in a statistically significant improvement in the CR rate or progression-free survival, but both were numerically improved in the atorvastatin arm. These data warrant further investigation into the potential therapeutic role of atorvastatin added to anthracycline-based chemotherapies.

Black sexually minoritized men (SMM) and transgender women (TW) are subgroups with lower rates of substance use and comparable rates of condom use relative to White SMM and TW yet experience heightened vulnerability to HIV. This study sought to explore associations of substance use, including sex-drug use (i.e., drug or alcohol use during sex to enhance sex), and condomless sex among Black SMM and TW. Data were collected from Black SMM and TW living in Chicago, Illinois, enrolled in the Neighborhoods and Networks (N2) cohort study, from November 2018 to April 2019. We used bivariate analyses followed by a multilevel egocentric network analysis to identify factors associated with condomless sex. We conducted Spearman correlation coefficients to examine correlations between pairs of sex-drugs to enhance sex. We used a bipartite network analysis to identify correlates of sex-drug use and condomless sex. A total of 352 Black SMM and TW (egos) provided information about 933 sexual partners (alters). Of respondents, 45% reported condomless sex and 61% reported sex-drug use. In unadjusted analyses, marijuana (34%) and cocaine/crack (5%) sex-drug use were associated with condomless sex (p < 0.05). Condomless sex was positively associated with sex-polydrug use, or the use of 2+ drugs or 1 drug and alcohol (OR = 1.48; 95% CI: 1.02-2.14; p = 0.039), and negatively associated with sharing an HIV-negative serostatus with a sexual partner (OR = 0.57; 95% CI: 0.33-0.98; p = 0.041), having a different HIV serostatus with a sexual partner (OR = 0.37; 95% CI: 0.21-0.64; p < 0.001) or not knowing the HIV serostatus of a sexual partner (OR = 0.47; 95% CI: 0.26-0.84; p = 0.011). The following pairs of sex-polydrug use had Spearman correlation coefficients higher than 0.3: marijuana and alcohol, ecstasy and alcohol, cocaine/crack and ecstasy, and methamphetamine and poppers (p < 0.05). HIV prevention interventions for Black SMM and TW designed to reduce HIV transmission through egocentric sexual networks could address sex-drug use through sex-positive and pleasure-centered harm reduction strategies and provide and promote biomedical prevention and care options at supraoptimal levels., (© 2024. Society for Prevention Research.)

Advances in HIV prevention tools have outpaced our ability to ensure equitable access to these tools. Novel approaches to reducing known barriers to accessing HIV prevention, such as stigma and logistical-related factors, are urgently needed. To evaluate the efficacy of a randomized controlled trial with four intervention arms to address barriers to HIV/STI testing uptake (primary outcome) and PrEP use, depression, and HIV test results (secondary outcomes). We tested a 2 × 2 research design: main effect 1-stigma-focused vs. health information evaluation-focused counseling, main effect 2-offering HIV/STI testing appointments in person vs. at home with a counselor via video chat, and the interaction of the main effects. Participants (N = 474) residing in the southeastern USA were screened and enrolled in a longitudinal trial. Intervention efficacy was established using generalized linear modeling with binomial or Poisson distributions. Intervention efficacy demonstrated an increase in HIV/STI testing uptake when testing was made available at home with a counselor via video chat vs. in person (83% vs. 75% uptake, p < .05), and participants were also more likely to test positive for HIV over the course of the study in the at-home condition (14.5% vs. 9.4%, p < .05). Stigma-focused counseling resulted in lower depression scores and greater uptake of PrEP among participants < 30 years of age when compared with health information counseling (15.4% vs. 9.6%, p < .05). In order to prevent further disparities between HIV prevention advances and access to HIV prevention tools, we must prioritize improvements in linking people to care. Novel interventions, such as those proposed here, offer a practical, evidence-based path to addressing long-standing barriers to HIV prevention strategies. Trial registration: NCT03107910., (© 2023. Society for Prevention Research.)

Abstract: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition of multiple myeloma with few known risk factors. The emergence of mass spectrometry (MS) for the detection of MGUS has provided new opportunities to evaluate its risk factors. In total, 2628 individuals at elevated risk for multiple myeloma were enrolled in a screening study and completed an exposure survey (PROMISE trial). Participant samples were screened by MS, and monoclonal proteins (M-proteins) with concentrations of ≥0.2 g/L were categorized as MS-MGUS. Multivariable logistic models evaluated associations between exposures and MS outcomes. Compared with normal weight (body mass index [BMI] of 18.5 to <25 kg/m2), obesity (BMI of ≥30 kg/m2) was associated with MS-MGUS, adjusting for age, sex, Black race, education, and income (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.21-2.47; P = .003). High physical activity (≥73.5 metabolic equivalent of task (MET)-hours per week vs <10.5 MET-hours per week) had a decreased likelihood of MS-MGUS (OR, 0.45, 95% CI, 0.24-0.80; P = .009), whereas heavy smoking and short sleep had increased likelihood of MS-MGUS (>30 pack-years vs never smoker: OR, 2.19; 95% CI, 1.24-3.74; P = .005, and sleep <6 vs ≥6 hours per day: OR, 2.11; 95% CI, 1.26-3.42; P = .003). In the analysis of all MS-detected monoclonal gammopathies, which are inclusive of M-proteins with concentrations of <0.2 g/L, elevated BMI and smoking were associated with all MS-positive cases. Findings suggest MS-detected monoclonal gammopathies are associated with a broader range of modifiable risk factors than what has been previously identified. This trial was registered at www.clinicaltrials.gov as #NCT03689595., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Obesity is an established, modifiable risk factor of multiple myeloma (MM); yet, no lifestyle interventions are routinely recommended for patients with overweight or obesity with MM precursor conditions. Prolonged nightly fasting is a simple, practical dietary regimen supported by research, suggesting that the synchronization of feeding-fasting timing with sleep-wake cycles favorably affects metabolic pathways implicated in MM. We describe the design and rationale of a randomized controlled pilot trial evaluating the efficacy of a regular, prolonged nighttime fasting schedule among individuals with overweight or obesity at high risk for developing MM or a related lymphoid malignancy., Objective: We aim to investigate the effects of 4-month prolonged nightly fasting on body composition and tumor biomarkers among individuals with overweight or obesity with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or smoldering Waldenström macroglobulinemia (SWM)., Methods: Individuals with MGUS, SMM, or SWM aged ≥18 years and a BMI of ≥25 kg/m 2 are randomized to either a 14-hour nighttime fasting intervention or a healthy lifestyle education control group. Participants' baseline diet and lifestyle patterns are characterized through two 24-hour dietary recalls: questionnaires querying demographic, comorbidity, lifestyle, and quality-of-life information; and wrist actigraphy measurements for 7 days. Fasting intervention participants are supported through one-on-one telephone counseling by a health coach and automated SMS text messaging to support fasting goals. Primary end points of body composition, including visceral and subcutaneous fat (by dual-energy x-ray absorptiometry); bone marrow adiposity (by bone marrow histology); and tumor biomarkers, specifically M-proteins and serum free light-chain concentrations (by gel-based and serum free light-chain assays), are assessed at baseline and after the 4-month study period; changes therein from baseline are evaluated using a repeated measures mixed-effects model that accounts for the correlation between baseline and follow-up measures and is generally robust to missing data. Feasibility is assessed as participant retention (percent dropout in each arm) and percentage of days participants achieved a ≥14-hour fast., Results: The PROlonged nightly FASTing (PROFAST) study was funded in June 2022. Participant recruitment commenced in April 2023. As of July 2023, six participants consented to the study. The study is expected to be completed by April 2024, and data analysis and results are expected to be published in the first quarter of 2025., Conclusions: PROFAST serves as an important first step in exploring the premise that prolonged nightly fasting is a strategy to control obesity and obesity-related mechanisms of myelomagenesis. In evaluating the feasibility and impact of prolonged nightly fasting on body composition, bone marrow adipose tissue, and biomarkers of tumor burden, this pilot study may generate hypotheses regarding metabolic mechanisms underlying MM development and ultimately inform clinical and public health strategies for MM prevention., Trial Registration: ClinicalTrials.gov NCT05565638; http://clinicaltrials.gov/ct2/show/NCT05565638., International Registered Report Identifier (irrid): DERR1-10.2196/51368., (©David J Lee, Elizabeth K O'Donnell, Noopur Raje, Cristina Panaroni, Robert Redd, Jennifer Ligibel, Dorothy D Sears, Omar Nadeem, Irene M Ghobrial, Catherine R Marinac. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 11.03.2024.)

Uptake of HIV testing is a critical step in the HIV prevention and treatment care cascade. Barriers to HIV testing, however, remain and innovative research in this area is warranted to improve uptake of testing. As such, we investigated the role of HIV information avoidance - a novel construct potentially related to HIV testing. We analyzed this construct in relation to other factors known to impact HIV testing, namely HIV stigma and medical mistrust. Multiple linear regression analyses indicated that HIV information avoidance was negatively associated with HIV testing, while medical mistrust was positively associated with HIV testing. HIV testing stigma was not associated with HIV testing. This work contributes to the developing literature on HIV information avoidance and its relationships with HIV stigma and HIV testing uptake. Further, these findings can inform HIV testing interventions which often do not focus on HIV information avoidance. Future research on the mechanisms of information avoidance that are amenable to intervention, and the temporal ordering of the relationship between information avoidance and HIV testing is warranted., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Clonal hematopoiesis (CH) at time of autologous stem cell transplant (ASCT) has been shown to be associated with decreased overall survival (OS) and progression-free survival (PFS) in patients with multiple myeloma not receiving immunomodulatory drugs (IMiD). However, the significance of CH in newly diagnosed patients, including transplant ineligible patients, and its effect on clonal evolution during multiple myeloma therapy in the era of novel agents, has not been well studied. Using our new algorithm to differentiate tumor and germline mutations from CH, we detected CH in approximately 10% of 986 patients with multiple myeloma from the Clinical Outcomes in MM to Personal Assessment of Genetic Profile (CoMMpass) cohort (40/529 transplanted and 59/457 non-transplanted patients). CH was associated with increased age, risk of recurrent bacterial infections and cardiovascular disease. CH at time of multiple myeloma diagnosis was not associated with inferior OS or PFS regardless of undergoing ASCT, and all patients benefited from IMiD-based therapies, irrespective of the presence of CH. Serial sampling of 52 patients revealed the emergence of CH over a median of 3 years of treatment, increasing its prevalence to 25%, mostly with DNMT3A mutations., Significance: Using our algorithm to differentiate tumor and germline mutations from CH mutations, we detected CH in approximately 10% of patients with newly diagnosed myeloma, including both transplant eligible and ineligible patients. Receiving IMiDs improved outcomes irrespective of CH status, but the prevalence of CH significantly rose throughout myeloma-directed therapy., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Background: First-line treatment of diffuse large B-cell lymphoma (DLBCL) achieves durable remission in approximately 60% of patients. In relapsed or refractory disease, only about 20% achieve durable remission with salvage chemoimmunotherapy and consolidative autologous stem cell transplantation (ASCT). The ZUMA-7 (axicabtagene ciloleucel [axi-cel]) and TRANSFORM (lisocabtagene maraleucel [liso-cel]) trials demonstrated superior event-free survival (and, in ZUMA-7, overall survival) in primary-refractory or early-relapsed (high-risk) DLBCL with chimeric antigen receptor T-cell therapy (CAR-T) compared with salvage chemoimmunotherapy and consolidative ASCT; however, list prices for CAR-T exceed $400 000 per infusion., Objective: To determine the cost-effectiveness of second-line CAR-T versus salvage chemoimmunotherapy and consolidative ASCT., Design: State-transition microsimulation model., Data Sources: ZUMA-7, TRANSFORM, other trials, and observational data., Target Population: "High-risk" patients with DLBCL., Time Horizon: Lifetime., Perspective: Health care sector., Intervention: Axi-cel or liso-cel versus ASCT., Outcome Measures: Incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (iNMB) in 2022 U.S. dollars per quality-adjusted life-year (QALY) for a willingness-to-pay (WTP) threshold of $200 000 per QALY., Results of Base-Case Analysis: The increase in median overall survival was 4 months for axi-cel and 1 month for liso-cel. For axi-cel, the ICER was $684 225 per QALY and the iNMB was -$107 642. For liso-cel, the ICER was $1 171 909 per QALY and the iNMB was -$102 477., Results of Sensitivity Analysis: To be cost-effective with a WTP of $200 000, the cost of CAR-T would have to be reduced to $321 123 for axi-cel and $313 730 for liso-cel. Implementation in high-risk patients would increase U.S. health care spending by approximately $6.8 billion over a 5-year period., Limitation: Differences in preinfusion bridging therapies precluded cross-trial comparisons., Conclusion: Neither second-line axi-cel nor liso-cel was cost-effective at a WTP of $200 000 per QALY. Clinical outcomes improved incrementally, but costs of CAR-T must be lowered substantially to enable cost-effectiveness., Primary Funding Source: No research-specific funding., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-2276.

Data describing outcomes of chimeric antigen receptor (CAR) T-cell therapy in patients with secondary central nervous system (SCNS) involvement of mantle cell lymphoma (MCL) are limited. We identified 10 patients with MCL and SCNS involvement treated with anti-CD19 CAR T-cell therapy at three US academic centres. Frequent objective responses were observed in the CNS (86%) and systemically (90%), and the 1-year progression-free survival was 47%. Seven patients developed immune-effector-cell-associated-neurotoxicity-syndrome (n = 2 Grade 1, n = 5 Grade 3). Our results suggest that anti-CD19 CAR T-cell therapy in this setting is feasible and additional data regarding neurotoxicity in this population may be warranted., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Pre-exposure prophylaxis (PrEP) has demonstrated efficacy for HIV prevention, yet uptake of PrEP among populations in urgent need of prevention tools (eg, Black sexual minority men) is limited, and stigma and medical mistrust remain strong barriers to accessing PrEP., Purpose: To evaluate a test of concept brief intervention to address stigma and medical mistrust as barriers to PrEP uptake using novel latent profile analysis., Methods: Participants (N = 177) residing in the southeastern US were randomized to 1 of 4 arms to establish the potential impact of a brief, stigma focused counseling intervention (referred to as Jumpstart ) to increase PrEP uptake. We estimated intervention effect size (Cramer's V) for PrEP uptake and then explored differential intervention effects across latent profiles of psychosocial barriers to PrEP use., Results: The intervention resulted in small, but meaningful effect size, with self-reported PrEP uptake increasing across Jumpstart conditions with the control condition reporting 24% uptake and Jumpstart plus text/phone calls (the most intensive intervention arm) reporting 37% uptake, and a similar pattern emerging for biologically confirmed PrEP use. Among participants 30 and older, Jumpstart participants were more likely to move to a postintervention profile with fewer barriers than control participants and reported the highest uptake of PrEP., Conclusions: Addressing social/emotional barriers to PrEP uptake is an essential component of bridging the gap between advances being made in biomedical forms of HIV prevention, and establishing and supporting access to those advances., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Black sexual minority men (SMM) in the Deep South are heavily impacted by HIV; yet studies fail to consider discordance across aspects of sexual orientation (i.e., identity, attraction, behavior) or how a lack of concordance enhances vulnerability to HIV. We sought to explore the overlap across aspects of sexual orientation and examine associations between each aspect and the number of sexual partners who engaged in HIV vulnerability-enhancing behaviors, and HIV prevention and care outcomes. A total of 204 Black SMM completed surveys, reporting their sexual identity, attraction, and behavior (i.e., sex with men only vs. sex with men and women), number of condomless sex or transactional sex (e.g., buyers vs. sellers) partners in the past 6 months, and adherence to pre-exposure prophylaxis (PrEP) or antiretroviral therapy (ART) among users. Less than one in four participants (22.5%) reported overlap in same-sex sexual orientations, while 17.1% of bisexual men reported overlap across aspects. In multivariable models, differences were found in how aspects of sexual orientation were associated with the number of partners who bought or sold sex; as well as how often participants tested for HIV in the past 12 months. Results suggest different aspects of sexual orientation have implications for addressing HIV among Black SMM in the Deep South., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Individual-level behavior can be influenced by injunctive and descriptive social network norms surrounding that behavior. There is a need to understand how the influence of social norms within an individual's social networks may influence individual-level sexual behavior. We aimed to typologize the network-level norms of sexual behaviors within the social networks of Black sexual and gender minoritized groups (SGM) assigned male at birth. Survey data were collected in Chicago, Illinois, USA, between 2018 and 2019 from Black SGM. A total of 371 participants provided individual-level information about sociodemographic characteristics and HIV vulnerability from sex (i.e., condomless sex, group sex, use of alcohol/drugs to enhance sex) and completed an egocentric network inventory assessing perceptions of their social network members' (alters') injunctive and descriptive norms surrounding sexual behaviors with increased HIV vulnerability. We used Latent Profile Analysis (LPA) to identify network-level norms based on the proportion of alters' approval of the participant engaging in condomless sex, group sex, and use of drugs to enhance sex (i.e., injunctive norms) and alters' engagement in these behaviors (i.e., descriptive norms). We then used binomial regression analyses to examine associations between network-level norm profiles and individual-level HIV vulnerability from sex. The results of our LPA indicated that our sample experienced five distinct latent profiles of network-level norms: (1) low HIV vulnerability network norm, (2) moderately high HIV vulnerability network norm, (3) high HIV vulnerability network norm, (4) condomless sex dominant network norm, and (5) approval of drug use during sex dominant network norm. Condomless anal sex, group sex, and using drugs to enhance sex were positively and significantly associated with higher HIV vulnerability social network norm profiles, relative to low HIV vulnerability norm profiles. To mitigate Black SGM's HIV vulnerability, future HIV risk reduction strategies can consider using network-level intervention approaches such as opinion leaders, segmentation, induction, or alteration, through an intersectionality framework., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Drug development can be associated with slow timelines, particularly for rare or difficult-to-treat solid tumors such as glioblastoma. The use of external data in the design and analysis of trials has attracted significant interest because it has the potential to improve the efficiency and precision of drug development. A recurring challenge in the use of external data for clinical trials, however, is the difficulty in accessing high-quality patient-level data. Academic research groups generally do not have access to suitable datasets to effectively leverage external data for planning and analyses of new clinical trials. Given the need for resources to enable investigators to benefit from existing data assets, we have developed the Glioblastoma External (GBM-X) Data Platform which will allow investigators in neuro-oncology to leverage our data collection and obtain analyses. GBM-X strives to provide an uncomplicated process to use external data, contextualize single-arm trials, and improve inference on treatment effects early in drug development. The platform is designed to welcome interested collaborators and integrate new data into the platform, with the expectation that the data collection can continue to grow and remain updated. With such features, GBM-X is designed to help to accelerate evaluation of therapies, to grow with collaborations, and to serve as a model to improve drug discovery for rare and difficult-to-treat tumors in oncology., (©2023 American Association for Cancer Research.)

In the United States (U.S.), Black sexual minority men (BSMM) are disproportionately burdened by HIV. Prevention advances, such as HIV pre-exposure prophylaxis (PrEP), play a key role in reducing HIV transmission and improving our understanding of sexual expression and health. Despite these advances, little is known regarding the potential link between PrEP use and positive sexuality, including the benefits that BSMM see in accessing PrEP. We conducted a thematic analysis of 32 interviews with BSMM in the Southern U.S. regarding their PrEP beliefs. We developed five themes: (1) Sexual freedom , (2) Agency and empowerment , (3) Making PrEP normative , (4) Behavioral health practices , and (5) Committed relationship tensions . Our findings suggest that BSMM are increasingly concerned about freedom of choice and invested in sexual empowerment as related to their PrEP use. Further, unanticipated benefits, community support, and relationship tensions are salient factors in considerations of PrEP use among BSMM. These findings have implications for how we might understand a broader movement toward sexual empowerment and positivity, and the pivotal role that PrEP serves in this movement.

ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) with or without radiation has been the standard treatment for limited-stage Hodgkin lymphoma (HL) but carries risks of bleomycin lung injury and radiation toxicity. Brentuximab vedotin (BV) is approved with AVD for stage III-IV HL, but carries increased risks of peripheral neuropathy (PN) and neutropenic fever, likely due to overlapping toxicity between BV and vinblastine. We therefore evaluated BV in combination with AD for 4 or 6 cycles based on interim positron emission tomography response. Thirty-four patients with nonbulky stage I-II HL were enrolled. Risk was early favorable in 53% and unfavorable in 47%. The overall and complete response rates (CRRs) were 100% and 97%, respectively, with a 5-year progression-free survival (PFS) of 91%. No differences in outcome were observed based on stage (I vs II) or risk status (early favorable vs unfavorable). The most common adverse events were nausea (85%), peripheral sensory neuropathy (59%), and fatigue (56%). There were no cases of grade-4 neutropenia or neutropenic fever, and no patient received granulocyte-colony stimulating factor. Most cases of PN were grade 1, and no patient experienced grade ≥3 PN. BV-AD produced a high CRR and durable PFS with most patients requiring 4 cycles of therapy. Compared with BV-AVD, the toxicity profile appeared improved, with predominantly grade 1 reversible PN and no case of grade 4 neutropenia or neutropenic fever. This regimen warrants further study in HL and may serve as a backbone for the addition of novel agents. This trial is registered on clinicaltrials.gov (NCT02505269)., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Purpose: Intersecting experiences of stigma related to pre-exposure prophylaxis (PrEP) influence PrEP uptake among Black sexual minority men (BSMM) living in the southern United States; however, it is unclear what stigmatized identities and behaviors are impacted when accessing human immunodeficiency virus prevention options. To inform identity-specific PrEP interventions, this study examined stigma in BSMM's lives relating to intersecting experiences of PrEP stigma. Methods: We conducted 32 virtual, semistructured qualitative interviews with BSMM residing in the southeastern United States between February and April 2019. Results: We identified three themes (anticipated stigma, experiences of prejudice and stereotyping, and negative attitudes) and one subtheme within negative attitudes (othering social/sexual groups). Across all themes, PrEP stigma was often manifested through stigma against BSMM's sexual orientation or sexual behavior. BSMM in othering social/sexual groups displayed instances of cognitive dissonance by regularly expressing negative attitudes about and explicitly distancing themselves from social/sexual groups based on sexual orientation and sexual behavior. BSMM's race and gender were rarely mentioned as being stigmatized. Conclusions: Interventions focused on PrEP use could benefit from expanding their definition of PrEP stigma to include a stronger emphasis on intersecting identities and work to reduce cognitive dissonance in BSMM in the form of internalized homophobia.

Despite documented efficacy in reducing HIV transmission, pre-exposure prophylaxis (PrEP) uptake among Black sexual minority men (BSMM) is limited. One understudied factor which may impede PrEP uptake is PrEP-related interactive toxicity beliefs (i.e., believing it is hazardous to use alcohol/drugs while taking PrEP). Data from N = 169 HIV negative BSMM over 4 months showed high rates of agreement with at least one alcohol (78%) or drug (84%) interactive toxicity belief. Univariate analyses showed increased alcohol or drug interactive toxicity beliefs predicted lower PrEP uptake. Multivariable regression suggested those with PrEP-related alcohol or drug interactive toxicity beliefs were more likely to report high PrEP stigma, more negative PrEP beliefs (e.g., concern that taking PrEP disrupts life), and were more likely to use alcohol/drugs (respectively) prior to/during sex. Findings warrant intervention work targeting interactive toxicity beliefs with tailored messaging to mitigate PrEP stigma and correct concerns around substance use and PrEP.

Objective: The use of geosocial networking (GSN) apps to meet male sexual partners may contribute to HIV infection risk for Black men who have sex with men (MSM), but the psychosocial underpinnings of this behavior are not understood. In social psychology, the Rejection-Identification Model posits that identification with a socially stigmatized group emerges as a means of coping in response to perceived stigmatization-which can shape behavior. This study tested the Rejection-Identification process as a facilitator of increased use of GSN apps to meet male sexual partners among Black MSM who use these apps. Method: Black MSM ( N = 103; M age = 29.8) reporting a male sexual partner from a GSN app in the past year were recruited nationally from Grindr and Facebook. Participants completed an online survey in which they reported sociodemographic information, measures of racial stigma and Black identity, and characteristics of their past-year male sexual partners. Results: Participants in this sample reported that most of their past-year male partners came from GSN apps ( M percent = 82.3), and results from hypothesis testing showed that greater perceived devaluation of Black people in society (i.e., public racial stigma) was associated with an increased percentage of GSN-met partners. In line with the Rejection-Identification Model, this relationship was mediated by greater Black identity centrality. Conclusions: Findings highlight psychosocial correlates of increased GSN app use to meet male sexual partners among Black MSM, which may place Black MSM at increased risk for HIV infection. Results also point to the possibility that these factors may be harnessed to develop HIV prevention strategies for Black MSM. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Patients with precursors to multiple myeloma are dichotomised as having monoclonal gammopathy of undetermined significance or smouldering multiple myeloma on the basis of monoclonal protein concentrations or bone marrow plasma cell percentage. Current risk stratifications use laboratory measurements at diagnosis and do not incorporate time-varying biomarkers. Our goal was to develop a monoclonal gammopathy of undetermined significance and smouldering multiple myeloma stratification algorithm that utilised accessible, time-varying biomarkers to model risk of progression to multiple myeloma., Methods: In this retrospective, multicohort study, we included patients who were 18 years or older with monoclonal gammopathy of undetermined significance or smouldering multiple myeloma. We evaluated several modelling approaches for predicting disease progression to multiple myeloma using a training cohort (with patients at Dana-Farber Cancer Institute, Boston, MA, USA; annotated from Nov, 13, 2019, to April, 13, 2022). We created the PANGEA models, which used data on biomarkers (monoclonal protein concentration, free light chain ratio, age, creatinine concentration, and bone marrow plasma cell percentage) and haemoglobin trajectories from medical records to predict progression from precursor disease to multiple myeloma. The models were validated in two independent validation cohorts from National and Kapodistrian University of Athens (Athens, Greece; from Jan 26, 2020, to Feb 7, 2022; validation cohort 1), University College London (London, UK; from June 9, 2020, to April 10, 2022; validation cohort 1), and Registry of Monoclonal Gammopathies (Czech Republic, Czech Republic; Jan 5, 2004, to March 10, 2022; validation cohort 2). We compared the PANGEA models (with bone marrow [BM] data and without bone marrow [no BM] data) to current criteria (International Myeloma Working Group [IMWG] monoclonal gammopathy of undetermined significance and 20/2/20 smouldering multiple myeloma risk criteria)., Findings: We included 6441 patients, 4931 (77%) with monoclonal gammopathy of undetermined significance and 1510 (23%) with smouldering multiple myeloma. 3430 (53%) of 6441 participants were female. The PANGEA model (BM) improved prediction of progression from smouldering multiple myeloma to multiple myeloma compared with the 20/2/20 model, with a C-statistic increase from 0·533 (0·480-0·709) to 0·756 (0·629-0·785) at patient visit 1 to the clinic, 0·613 (0·504-0·704) to 0·720 (0·592-0·775) at visit 2, and 0·637 (0·386-0·841) to 0·756 (0·547-0·830) at visit three in validation cohort 1. The PANGEA model (no BM) improved prediction of smouldering multiple myeloma progression to multiple myeloma compared with the 20/2/20 model with a C-statistic increase from 0·534 (0·501-0·672) to 0·692 (0·614-0·736) at visit 1, 0·573 (0·518-0·647) to 0·693 (0·605-0·734) at visit 2, and 0·560 (0·497-0·645) to 0·692 (0·570-0·708) at visit 3 in validation cohort 1. The PANGEA models improved prediction of monoclonal gammopathy of undetermined significance progression to multiple myeloma compared with the IMWG rolling model at visit 1 in validation cohort 2, with C-statistics increases from 0·640 (0·518-0·718) to 0·729 (0·643-0·941) for the PANGEA model (BM) and 0·670 (0·523-0·729) to 0·879 (0·586-0·938) for the PANGEA model (no BM)., Interpretation: Use of the PANGEA models in clinical practice will allow patients with precursor disease to receive more accurate measures of their risk of progression to multiple myeloma, thus prompting for more appropriate treatment strategies., Funding: SU2C Dream Team and Cancer Research UK., Competing Interests: Declaration of interests This study was previously presented on April 12, 2022, at the 2022 American Association for Cancer Research Annual Meeting and on Aug 25, 2022, at the International Myeloma Society Annual Meeting. AC declares grants from the International Myeloma Society for travel and conference expenses. FF is employed by Biostatistics and Research Decision Sciences, Merck & Co. SSF declares that their salary is partly supported by research funding from International Business Machines (IBM) and has patent applications (EP14807512·0A and US16/084 890) and a provisional patent application (62/866 261). LA declares grants from the International Myeloma Society for travel and conference expenses. JR declares honoraria from Sanofi, Janssen, Amgen, GSK, and Bristol Myers Squibb; travel grants from BMS, Janssen, and Amgen; and funding from a consulting or advisory role from Sanofi, Janssen, Amgen, GSK, and BMS. EK reports honoraria from Amgen, Janssen, Takeda, Genesis Pharma, Pfizer, and GSK; travel grants from Janssen; and is an advisory board member at Janssen and Prothena. MAD declares honoraria from Amgen, BMS, Takeda, and Janssen and is an advisory board member at Amgen, BMS, Takeda, and Janssen. CRM reports research funding from GRAIL. GG declares honoraria for lectures from Society for Neuro-oncology, Society of Tumor Oncology, and MD Anderson; honoraria as a Paul C Zamecnik Chair in Oncology; research funding from IBM and Pharmacyclics; patents, royalties, other intellectual property as Inventor on patent applications related to MSMuTect, MSMutSig, MSIDetect, POLYSOLVER, and SignatureAnalyzer-GPU; and stock and other ownership interests from Founder as a consultant and has privately-held equity in Scorpion Therapeutics. IMG declares honoraria from Celgene, Bristol-Myers Squibb, Takeda, Amgen, Janssen, and Vor Biopharma; consulting or advisory roles at Bristol-Myers Squibb, Novartis, Amgen, Takeda, Celgene, Cellectar, Sanofi, Janssen, Pfizer, Menarini Silicon Biosystems, Oncopeptides, The Binding Site, GSK, AbbVie, Adaptive, and 10xGenomics; and a spouse who is the Chief Medical Officer at Disc Medicine and holds equity in the company. AC, FF, SSF, GG, LT, and IMG have applied for a patent for the application of the PANGEA models described in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

While most patients with follicular lymphoma (FL) have excellent outcomes with frontline chemoimmunotherapy (CIT), a subset of patients will experience early progression, which is associated with poor subsequent outcomes. Novel biomarkers are needed to identify high-risk patients earlier. We hypothesized that interim positron emission tomography (PET) would predict progression-free survival (PFS) in this population. We retrospectively identified 128 patients with grade 1-3A FL who had an interim PET after 2-4 cycles of frontline CIT at 2 academic centers. PET scans were analyzed using Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Interim PET DS was a significant predictor of PFS ( P < 0.003). Patients with a DS of 3 had outcomes similar to those of patients with a DS of 4, so were categorized as PET-positive for additional analyses. Interim PET remained a strong predictor of PFS (DS 3-5, hazard ratio [HR] 2.4, P = 0.006) in a multivariable analysis and was also an early predictor of both a positive end-of-treatment PET ( P < 0.001) and progression of disease within 24 months (POD24) ( P = 0.006). An optimal ΔSUVmax cutoff of 75% was selected using the bootstrap method. ΔSUVmax <75% was also a significant predictor of PFS on univariable and multivariable analyses (HR 2.8, P < 0.003). In a separate cohort of 50 patients with high-grade FL, interim PET interpreted using either DS ( P < 0.001) or ΔSUVmax75% ( P = 0.034) was also a significant predictor of inferior PFS. In conclusion, interim PET is an independent predictor of PFS and may be useful as a tool for response-adapted treatment strategies in FL., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)