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Treatment of relapsed/refractory multiple myeloma (RRMM) is challenging as patients exhaust all available therapies and the disease becomes refractory to standard drug classes. Here we report the final results of LocoMMotion, the first prospective study of real-world clinical practice (RWCP) in triple-class exposed (TCE) patients with RRMM, with a median follow-up of 26.4 months (range, 0.1–35.0). Patients (N=  248) had received median 4 prior LOT (range, 2–13) at enrollment. 91 unique regimens were used in index LOT. Overall response rate was 31.9% (95% CI, 26.1–38.0), median progression-free survival (PFS) was 4.6 months (95% CI, 3.9–5.6) and median overall survival was 13.8 months (95% CI, 10.8–17.0). 152 patients (61.3%) had subsequent LOTs with 134 unique regimens, of which 78 were used in first subsequent LOT. Median PFS2 (from start of study through first subsequent LOT) was 10.8 months (95% CI, 8.4–13.0). 158 patients died on study, 67.7% due to progressive disease. Additional subgroup analyses and long-term safety summaries are reported. The high number of RWCP treatment regimens utilized and poor clinical outcomes confirm a lack of standardized treatment for TCE patients with RRMM, highlighting the need for new treatments with novel mechanisms.

IntroductionIn ESCAPE-TRD (NCT04338321), a randomized, open-label, rater-blinded, long-term, phase 3b trial, augmentation with esketamine nasal spray (ESK) demonstrated increased probability of achieving meaningful clinical benefit versus quetiapine extended release (QUE XR) in patients (pts) with treatment-resistant depression (TRD). This subgroup analysis of ESCAPE-TRD evaluated the incidence, duration, and impact of treatment-emergent adverse events (TEAEs) on treatment discontinuation in adults with TRD treated with ESK or QUE XR according to US prescribing information.MethodsPts aged 18-64 years were randomly assigned to receive flexibly dosed ESK (56 or 84 mg) or QUE XR (150-300 mg), both consistent with US label dosing and in combination with an ongoing oral antidepressant. The incidence and duration of the most commonly occurring TEAEs, as well as the most common TEAEs leading to treatment discontinuation, were summarized descriptively. All randomly assigned participants receiving ≥1 dose of study drug were included in the safety analyses.ResultsAmong the 636 pts included in the subgroup analysis, 316 and 320 were randomly assigned to ESK and QUE XR, respectively; 314 and 316 were included in the safety population. In the combined acute and maintenance phases, TEAEs occurred in 92.0% of pts in the ESK group and 78.5% of pts in the QUE XR group. The most commonly reported TEAEs with ESK or QUE XR in the combined acute and maintenance phases were dizziness (47.1% and 7.9%, respectively), headache (25.5% and 13.0%, respectively), somnolence (15.0% and 23.4%, respectively), and nausea (29.9% and 3.2%, respectively). Across all TEAE events reported in >5% of pts in either arm, 91.8% (5831 of 6351) resolved within 1 day in the ESK arm compared to 11.6% (90 of 776) with QUE XR. For specific TEAE events of clinical interest for ESK, same-day resolution rates for increased blood pressure, sedation, and dissociation in the ESK group were 93.5% (116 of 124), 96.2% (127 of 132), and 99.6% (740 of 743), respectively. The majority of TEAEs of clinical interest in the ESK group that occurred on the same day of dosing resolved within the first 2 hours after dosing. For the most frequently reported TEAEs with QUE XR, same-day resolution rates for somnolence, headache, and fatigue were 7.8% (8 of 103), 49.2% (29 of 59), and 9.5% (4 of 42), respectively. Fewer pts treated with ESK discontinued treatment due to TEAEs compared to QUE XR (4.4% versus 10.6%).ConclusionsSafety data from this subgroup analysis were consistent with the overall study population as well as the known tolerability profile of each treatment. TEAEs were reported at higher incidence with ESK than with QUE XR; however, the majority of TEAEs occurring with ESK were transient in nature and did not result in a higher rate of treatment discontinuation compared to QUE XR.FundingJanssen Scientific Affairs, LLC

Objectives Gonococcal infections with a higher bacterial load may pose a higher risk of transmission. We assessed the association between gonococcal bacterial load and coinfection with Mycoplasma genitalium.Methods From September 2015 until May 2018, 200 men and transgender women who have sex with men participated in an HIV pre-exposure prophylaxis (PrEP) demonstration trial in Antwerp, Belgium. They underwent 3-monthly 3-site (anus, urine, and pharynx) molecular testing for N. gonorrhoeae and C. trachomatisand M. genitalium, irrespective of symptoms. Gonococcal bacterial load was determined on remnant DNA extracts using an in-house quantitative PCR. Results were expressed as log10transformed copies/mL and analyzed with a linear regression model.Results Gonococcal bacterial load could be determined for 82 (80.4%) of 102 anal, 17 (73.9%) of 23 urine, and 64 (90.1%) of 71 pharyngeal samples. M. genitaliumwas detected in five of these anal, two urine, and two pharyngeal samples and C. trachomatiswas detected in 16 anal, one urine, and two pharyngeal samples. Gonococcal bacterial load was significantly higher in the presence of M. genitalium(difference 0.92 log copies/mL, 95% CI 0.16–1.67).Conclusions Gonococcal bacterial load was higher with M. genitaliumcoinfection. M. genitaliummay thus be a cofactor in gonococcal transmission.

Background: Nail psoriasis is a common, physiologically, and psychologically disruptive, and yet often under-treated manifestation of psoriasis. The objectives of this analysis were to investigate the trajectory of nail psoriasis, a risk factor for psoriatic arthritis (PsA), with guselkumab vs adalimumab treatment followed by withdrawal, and determine characteristics associated with nail response in patients treated with guselkumab. Methods: This post hocanalysis of the phase III trial VOYAGE 2 included patients with moderate-to-severe plaque psoriasis and baseline nail involvement. Nail Psoriasis Severity Index (NAPSI) and Psoriasis Area and Severity Index (PASI) were analyzed through week 48 in patients randomized to guselkumab or adalimumab. Multiple logistic regression analyzed factors associated with NAPSI 0/1 at week 24/week 48 following guselkumab treatment. In a separate analysis, patients were stratified by prior biologic experience. Results: Overall, 272 vs 132 patients receiving guselkumab vs adalimumab had nail psoriasis at baseline. Lower baseline NAPSI and week 16 PASI were associated with achieving NAPSI 0/1 at week 24 (NAPSI, odds ratio 0.685 [95% confidence interval: 0.586, 0.802]; week 16 PASI, 0.469 [0.281, 0.782]) and week 48 (NAPSI, 0.784 [0.674, 0.914]; week 16 PASI, 0.557 [0.331, 0.937]) with guselkumab. Previous biologic experience did not impact NAPSI response. Following treatment withdrawal at week 28, mean NAPSI was maintained in the guselkumab arm (week 24 1.7, week 48 1.9) and increased slightly in the adalimumab arm (week 24 1.4, week 48 2.3). Mean PASI increased across both treatment arms. Conclusions: Higher skin efficacy at week 16 was associated with better nail responses during guselkumab treatment. Nail psoriasis improvements reflected skin improvements. Following guselkumab withdrawal, nail response was maintained longer than skin response. Future studies should investigate whether such improvements in nail response reduce patients’ risk of later PsA development. Trial registration: ClinicalTrials.gov, NCT02207244. Registered July 31, 2014.

Introduction:Patients (pts) with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM) represent a particularly difficult-to-treat population. A pooled analysis of the prospective, non-interventional, multinational LocoMMotion (NCT04035226) and MoMMent (NCT05160584) studies previously demonstrated suboptimal outcomes in pts with TCE RRMM. Extramedullary disease (EMD) is an aggressive feature of multiple myeloma characterized by the presence of plasmacytomas that have spread beyond the bone marrow. A recent systematic literature review (Bladé et al, 2022) found that the prognosis of pts with EMD is poor, as most current treatment (tx) options are notably less efficacious in pts with EMD than in those without EMD. The review also found that there are few prospective studies evaluating tx approaches in pts with EMD. Additional prospective data are needed to better understand current txs and outcomes for pts with EMD. In this analysis, we describe current txs and outcomes in pts with TCE RRMM with EMD over the past 3 years in LocoMMotion and MoMMent.

CD4 counts are currently used to assess HIV patients for treatment eligibility and to monitor antiretroviral response to treatment. The emerging point‐of‐care devices could fill an important gap in resource‐limited settings. However, the accuracy of CD4‐counting instruments is diverse and data on how CD4 measurement errors have an impact on clinical decisions are lacking. Clinicians were queried on the use of CD4 results in their clinical setting. Subsequently, the effect of CD4 measurement errors on treatment initiation was put in a statistical model. Based on clinical CD4 databases from Belgium, Cambodia, and Senegal, the percentage of unchanged clinical decisions was calculated (treatment initiation should start within a 3‐month delay [one visit]) for escalating CD4 measurement errors, taking into account the strict or preventive application of CD4 thresholds at 350 or 500 cells/µl used by clinicians. To ensure that the treatment was initiated appropriately for at least 95% of patients, an error of 5 − 10 cells/µl was allowed. This is significantly smaller than the bias of ±50 cells/µl most clinicians considered acceptable. For limits of agreement (LOA, 1.96 x error) of 100 cells/µl, corresponding to most CD4 instrument evaluations, the misclassification rate of patients was found to be 3 − 28% at the threshold of 350 cells/µl (strict or flexible), and 13 − 20% at 500 cells/µl. The maximum allowed CD4 bias on results from new CD4 technologies should not exceed 50 cells/µl (LOA 100 cells/µl) when applied for treatment initiation, to ensure at least 72% of correct clinical decisions. © 2016 International Clinical Cytometry Society

ObjectivesThe study aimed to test if there was an association between prevalent bacterial vaginosis (BV) and women reporting that their partner had other partners at the same time (partner concurrency). This association has not been assessed in a longitudinal cohort.MethodsThe Longitudinal Study of Vaginal Flora recruited a cohort of 3620 non-pregnant women aged 15–44 years who presented for routine primary healthcare at 12 clinics in Birmingham, Alabama. Behavioural questionnaires and vaginal smears were obtained quarterly for a year and BV was defined by a Nugent score 7 or higher as well as Amsel criteria. Mixed effects logistic regression was used to assess the relationship between prevalent BV and reporting that one's partner had other partners in the preceding 3–6 months time interval.ResultsNugent score prevalent BV was associated with both reporting that one's partner definitely (adjusted OR (aOR) 1.5; 95% CI 1.2 to 1.8) and possibly (aOR 1.5; 95% CI 1.2 to 1.8) engaged in partner concurrency in the preceding 3–6 months time period. Prevalent BV diagnosed by Amsel criteria was similar.ConclusionsA diagnosis of prevalent BV was associated with reporting that one's partner possibly or definitely engaged in partner concurrency.