Citations

Background Reductions in blood pressure (BP) control among patients with hypertension were observed early in the COVID‐19 pandemic. The degree to which BP control may have returned to prepandemic levels is unknown. Methods Individuals aged 18 to 85 years with hypertension from 17 health systems participating in the National Patient‐Centered Clinical Research Network were identified using electronic health record data collected as part of routine care. BP control (percentage of patients whose most recent BP measurement was <140/<90 mm Hg) was estimated in a series of 12‐month rolling measurement periods from 2017 through 2022 (January 1, 2017 through December 31, 2017; April 1, 2017 through March 31, 2018; … January 1, 2022 through December 31, 2022). Differences in average BP control between 2022 (January 1, 2022 through December 31, 2022) and 2019 (January 1, 2019 through December 31, 2019) were estimated overall (adjusted for age, sex, and race and ethnicity) and by race and ethnicity (adjusted for age and sex). Results Our sample included 1 193 314 persons with hypertension in 2019 (48.9% aged 65–85 years, 52.9% men, 66.2% non‐Hispanic White) and 1 499 418 individuals in 2022 (50.6% aged 65–85 years, 47.1% men, 62.7% non‐Hispanic White). The weighted average BP control dropped from 65.3% in 2019 to 61.8% in 2020 and then partially recovered to 62.6% in 2022 (adjusted mean difference, −2.6 percentage points [95% CI, −5.0 to −0.2]). Non‐Hispanic Asian individuals experienced the largest temporal drop in BP control, declining from 68.4% in 2019 to 63.9% in 2022. Conclusions BP control was disrupted during the COVID‐19 pandemic and had not fully rebounded to prepandemic levels by the end of 2022. Continued surveillance is needed to determine whether the decline in BP control will persist and will result in future adverse cardiovascular events.

Abstract Background: Multiple myeloma is the second most common adult blood cancer and remains incurable, despite recent advances. The IMWG/IMS recently published updated risk criteria, Consensus Genomic Staging (CGS), combining genomic events with clinical measures to identify high-risk patients (Avet-Loiseau, et al. JCO 2025). We applied CGS risk criteria to baseline samples from the Multiple Myeloma Research Foundation CoMMpass Study (NCT01454297), a prospective, longitudinal observational study that enrolled more than1100 participants between 2011-2017. Methods: We assessed patient risk following CGS criteria. Criteria 1: del(17p), with a cutoff of &gt;20% clonal fraction, and/or TP53 mutation. Criteria 2: an IgH translocation including t(4;14), t(14;16), or t(14;20) along with 1q+ and/or del(1p32). Criteria 3: monoallelic del(1p32) along with 1q+ or biallelic del(1p32). Criteria 4: beta-2 microglobulin &gt;= 5.5 mg/L with normal creatinine. Patients meeting one or more criteria were classified as High Risk. To test if risk showed association with genetic ancestry, we grouped patients into those with high African genetic ancestry and those with low African genetic ancestry. Genetic ancestry was measured using ADMIXTURE in comparison to 1000 Genomes. Results: We evaluated the CGS risk status of 877 CoMMpass patients, finding 69.2% (573/828) to be Standard Risk (SR) and 30.8% (255/828) to be High Risk (HR). HR patients showed worse progression-free survival (median PFS 26.3 months vs. 42.5 months; log rank test, p &lt; 0.0001) and overall survival (median OS 63.9 months vs. median not reached; p &lt; 0.0001). 10.6% (91/858) of patients met Criteria 1, 10.7% (93/873) met Criteria 2, 5.6% (49/877) met Criteria 3, and 8.7% (73/835) met Criteria 4. We found 14.2% (123/867) of patients to have high African-like genetic ancestry (AFR-high) and 85.8% (744/867) to have low African-like genetic ancestry (AFR-low). We observed significantly fewer HR patients within the AFR-high group (20%, 23/115) than in the AFR-low group (32.4%, 231/712) (Fisher’s exact test, p = 0.0065). The AFR-high group met HR criteria at a lower rate across all criteria, but only with Criteria 3 was the difference significant (p-value = 0.03). Higher levels of creatinine in AFR-high patients may have impacted meeting the normal creatinine requirement of Criteria 4. Conclusions: HR patients comprise 30.8% of CoMMpass subjects and show significantly worse PFS and OS than SR patients. AFR-high patients met HR criteria at a lower rate than AFR-low patients according to the CGS criteria. Clinical trials that utilize CGS criteria to determine patient eligibility may be challenged to enroll a representative patient population, including AFR-high patients. Screening and eligibility criteria should be carefully considered to mitigate potential enrollment disparities. Citation Format: Steven M. Foltz, Chaitanya R. Acharya, Alexander Gout, Yuxin Jin, David E. Avigan, Ravi Vij, Shaji Kunnathu Kumar, Sagar Lonial, Hearn Cho, Katie Wozniak, Jonathan J. Keats, Craig Cole, John D. Carpten, George J. Mulligan. Multiple myeloma risk classification of CoMMpass using Consensus Genomic Staging identifies differences between patients with high and low African genetic ancestry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3887.

ABSTRACT Background Secukinumab, a fully human, monoclonal antibody targeting interleukin‐17A, is approved for moderate‐to‐severe HS in adults. This study evaluated pharmacokinetics (PK), high‐sensitivity C‐reactive protein (hsCRP) changes, and safety of secukinumab over 52 weeks in SUNSHINE and SUNRISE Phase 3 trials. Methods An exploratory analysis of pooled Phase‐3 trials evaluated serum PK and safety of secukinumab 300 mg every 2 (SECQ2W) or 4 weeks (SECQ4W). A population PK model assessed the effects of body weight, disease severity, and baseline hsCRP on secukinumab serum concentration. Exposure–response analysis assessed the relationship between predicted PK and HS clinical response [HiSCR]. No confirmatory statistical testing was performed. Results Mean serum trough concentration at Weeks 16, 24, and 52 was ~2‐fold higher with SECQ2W vs. SECQ4W. At Week 16, exposure overlap was high, with an estimated numerical increase in HiSCR of ~3% for SECQ2W over SECQ4W. At Week 52, HiSCR levels plateaued. At Week 16, hsCRP decreased from 18.6 ± 26.3 mg/L to 12.8 ± 18.0 mg/L (SECQ2W), 15.9 ± 27.6 mg/L to 11.5 ± 18.4 mg/L (SECQ4W), and remained unchanged with placebo (14.4 ± 22.5 mg/L to 14.7 ± 23.8 mg/L); reductions were sustained through Week 52. Higher body weight, disease severity, and baseline hsCRP were associated with lower secukinumab serum concentrations. Secukinumab immunogenicity was low (< 1%), with no new safety signals. Conclusion Secukinumab serum concentrations in patients with HS varied with body weight, disease severity, and baseline hsCRP. SECQ2W may benefit certain patients. Secukinumab reduced hsCRP through Week 52. The safety profile of secukinumab was consistent with other approved indications, with no apparent dose–response relationship observed. Trial Registration NCT03713619 (Novartis study code CAIN457M2301). NCT03713632 (Novartis study code CAIN457M2302)

3011 Background: BMS-986504 selectively binds to the PRMT5-MTA complex, which represents a synthetic lethal target in MTAP -del cancer cells, while sparing MTAP– wild-type cells. In the first-in-human phase 1/2 CA240-0007 study in advanced, unresectable or metastatic solid tumors with homozygous MTAP -del, BMS-986504 was found to be well tolerated and demonstrated antitumor activity in multiple tumors. Here, we report clinical results and the first PK and PD analyses of BMS-986504 from the dose escalation and expansion phases of CA240-0007. Methods: Pts with measurable/evaluable disease and no available treatment (Tx) with curative intent were enrolled; 7 doses were evaluated (50 to 800 mg) in dose escalation. Objective response rate (ORR), disease control rate (DCR), duration of response (DOR), time to response (TTR), safety, PK, PD, including plasma SDMA were assessed. Results: As of 2 Dec 24, 152 heavily pretreated pts were enrolled across all doses: NSCLC (n = 34), PDAC (n = 41), cholangiocarcinoma (n = 12), and mesothelioma (n = 12) were the most common tumor types. With a median f/u of 9.0 mo (95% CI 7.6–9.9), continued durable antitumor activity and deepening tumor regression were seen across tumor types and doses (ORR = 23%, DCR = 70%, median DOR = 10.5 mo, TTR = 4.6 mo). No new safety signals were identified. Most Tx-related adverse events (TRAEs) were grade (Gr) 1 or 2; 13% had Gr ≥ 3 TRAEs (Gr 3 = 12%, Gr 4 = < 1%, Gr 5 = 0). Doses from 50 to 600 mg QD were assessed for PK/PD. The AUC (0-24) after multiple doses was approximately dose proportional at 200 to 600 mg, and the terminal t 1/2 after a single dose was approximately 24 h (table). There were dose-dependent reductions in predicted plasma SDMA, with the 400 and 600 mg doses approaching the plateau. Conclusions: With longer f/u, BMS-986504 continued to show increasingly durable antitumor activity. BMS-986504 demonstrated a favorable PK/PD profile, supporting QD dosing at 400 and 600 mg. These results support further investigation of BMS-986504 at 400 and 600 mg QD as a potential first-in-class synthetic lethal Tx option in pts with advanced solid tumors with MTAP -del. Clinical trial information: NCT05245500 . PK and PD. 50 mg QD 100 mg QD 200 mg QD 400 mg QD 600 mg QD PK after multiple doses t max a (min–max), h 2.0 (2.0–4.0)n = 3 2.0 (1.0–2.0)n = 3 2.0 (0.5–6.0)n = 8 2.0 (0.5–4.0)n = 10 2.0 (1.0–6.0)n = 10 C max , b ng/mL 107n = 3 377n = 3 685n = 8 1240n = 10 2110n = 10 AUC (0-24) , b h∙ng/mL 948 n = 3 3060 n = 3 7150 n = 7 11,800n = 10 26,700n = 9 AUC (0-24) , b,c h∙ng/mL/mg 19.0n = 3 30.6n = 3 35.8n = 7 29.5n = 10 44.6n = 9 Terminal t 1/2 after single dose, d h 21.7 n = 1 80.7 n = 1 21.5 n = 14 21.7 n = 14 24.1 n = 1 PD Translational exposure targets (C avgss ), X 0.08 0.21 0.5 1.1 1.7 Predicted plasma SDMA reduction, a % (90% PI) 30.0 (23.2–37.8) 38.8 (27.1–47.5) 48.3 (42.0–53.0) 55.0 (50.7–57.6) 57.4 (54.3–59.0) a Median. b Geometric mean. c Dose-normalized. d Arithmetic mean.

Abstract Background: Effective treatments (Tx) are needed for MTAP-del cancers (10-15% of all cancers). BMS-986504 (formerly MRTX1719) is a potential first-in-class MTA-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor that selectively binds to the PRMT5-MTA complex, a synthetic lethal target in MTAP-del but not MTAP-wild-type cells. In the first-in-human phase 1/2 CA240-0007 study, BMS-986504 was well tolerated and showed clinical activity in heavily pretreated pts across multiple advanced solid tumors with homozygous MTAP-del. Here, we report results of exploratory PD analyses of PRMT5 inhibition with BMS-986504 in CA240-0007. Methods: Pts with advanced, unresectable or metastatic solid tumors with homozygous MTAP-del received BMS-986504 (50 to 800 mg) in 3-wk cycles. Symmetric dimethylarginine (SDMA) and intron retention are known PD BMs of PRMT5 inhibition. Therefore, PD effects of BMS-986504 were assessed via changes in plasma and tumor SDMA levels (mass spec and IHC), intron retention, and gene expression (RNASeq) based on samples collected at baseline (BL) and cycle 2 day 1 (C2D1). Additional analyses correlating efficacy outcomes with PD results and select mutations at BL were performed in clinically evaluable pts as of 19-SEP-24. Results: Robust PD modulation of the PRMT5 pathway was observed with BMS-986504. Among pts with matched samples (n = 63), median plasma SDMA levels were reduced by 56% from BL (122.6 ng/mL) to C2D1 (53.8 ng/mL). There were dose-dependent reductions in median plasma SDMA with the greatest reductions at 400 mg QD (59.7% [n = 20]), 400 mg BID (61.9% [n = 9]) and 600 mg QD (59.1% [n = 14]). These PD effects were corroborated in the tumor. Median tumor SDMA levels decreased from an HScore of 285 at BL to 0 at C2D1. Consistent with the SDMA decreases, increased intron retention was observed in 9/11 pts with matched samples. BMS-986504 led to downregulation of several gene pathways including DNA repair and mitotic spindle formation, and MYC and E2F targets, as assessed by RNASeq. There was no significant change in expression of MAT2A, PRMT5, or other PRMT genes, suggesting a lack of compensation for PRMT5 inhibition through these genes. Responses were observed with BMS-986504 across EGFR, KRAS, and TP53 mutation subgroups. Additional correlative analyses among BMs and efficacy outcomes will be presented. Conclusions: BMS-986504 demonstrated robust PD effects across multiple doses and solid tumors which is consistent with the proposed mechanism of action. There was a trend of increasing plasma SDMA reduction across doses, with the greatest reductions observed at 400 mg QD and above. Together these results support further investigation of BMS-986504 at 400 mg QD and higher doses as a potential first-in-class synthetic lethal Tx option in pts with advanced solid tumors with MTAP-del. Citation Format: Jordi Rodón, Tyler Simpson, Ben George, Pasi A. Jänne, Kathryn C. Arbour, Konstantinos Leventakos, Kyriakos P. Papadopoulos, Melissa L. Johnson, Alexander I. Spira, Cesar A. Perez, Hani M. Babiker, Richard Zuniga, Candace L. Haddox, Tapsi Kumar, Yidi Qin, Wen-Chi Chou, Peter Olson, Kenna Anderes, Alice Wozniak, Curtis Chin, Ming Lei, Jason T. Henry. Pharmacodynamic (PD) and exploratory biomarker (BM) analysis of the PRMT5 inhibitor BMS-986504 in patients (pts) with advanced solid tumors with homozygous MTAP deletion (MTAP-del) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT079.

AbstractIntroductionThe International Hidradenitis Suppurativa Severity Score System (IHS4) is a validated tool that measures inflammatory lesions, including draining tunnels, in hidradenitis suppurativa (HS).ObjectiveTo evaluate secukinumab efficacy using IHS4 in patients with moderate to severe HS.MethodsData from the SUNSHINE and SUNRISE trials, which assessed subcutaneous secukinumab 300 mg every 2 (SECQ2W) and 4 (SECQ4W) weeks in adults with moderate to severe HS, were analyzed. Assessments included changes from baseline in IHS4 and severity classification up to Week 52; IHS4‐55, IHS4‐75, IHS4‐90 responses (55%, 75% and 90% reduction in IHS4) and concordance between IHS4‐55 and HS clinical response (HiSCR), at Weeks 16 and 52.ResultsIn total, 1084 patients (SECQ2W = 361; SECQ4W = 360; placebo = 363) were analyzed. At Week 16, SECQ2W and SECQ4W demonstrated a numerically higher reduction in IHS4 from baseline versus placebo (adjusted mean [95% CI]: −10.80 [−12.30 to −9.30] and −9.46 [−10.96 to −7.96] vs. −4.92 [−6.43 to −3.41]); the reduction was maintained until Week 52 in both dose regimens. A greater proportion of patients achieved IHS4‐55 with SECQ2W (43.4%) and SECQ4W (39.5%) versus placebo (31.5%) at Week 16, with further improvement at Week 52. Similar trends were observed for IHS4‐75 and IHS4‐90 responses. While no patients had mild disease based on IHS4 (80.7% had severe and 19.3% had moderate HS) at baseline, a greater proportion of patients were categorized as having mild disease at Week 16 in the SECQ2W (25.9%) and SECQ4W (24.0%) groups versus placebo (16.4%); this trend continued up to Week 52 in both dose regimens. Strong concordance (>85%) was observed between IHS4‐55 and HiSCR.ConclusionsBoth SECQ2W and SECQ4W demonstrated efficacy in improving treatment response as measured by IHS4 and reducing disease severity versus placebo at Week 16 and these improvements were sustained through Week 52. These findings support that the dynamic and dichotomous IHS4 can efficiently detect treatment response changes in clinical trial settings.Clinical Trials RegistrationSUNSHINE (NCT03713619); SUNRISE (NCT03713632).

Background: The COVID-19 pandemic resulted in reduced in-person clinic visits and declines in blood pressure (BP) control among patients with hypertension. The purpose of this study was to report on pre- to post-pandemic trends in BP control and related BP metrics through 2022. Methods: We utilized data from 17 US health systems with electronic health record data standardized to the PCORnet ® Common Data Model. Multiple BP control metrics were calculated as a series of quarterly, 12-month rolling measurement periods from 2017 to 2022 (i.e., 1/1/2017-12/31/2017, 4/1/2017-3/31/2018, …, 1/1/2022-12/31/2022). BP control was defined as the percentage of patients with hypertension whose most recent BP measurement at an ambulatory visit was <140/<90 mmHg. Improvement in BP was defined as the percentage of patients with a reduction of 10 mmHg in systolic BP or achievement of systolic BP <140 mmHg during the last 3 months of the measurement period in patients with previously uncontrolled hypertension. Results: In 2022, 1,499,418 persons with hypertension were included (50% 65-85 years old; 47% men; 11% Hispanic, 3% non-Hispanic Asian, 20% non-Hispanic Black, 63% non-Hispanic White). BP control was relatively stable within health systems prior to the COVID-19 pandemic. Worsening of BP control was seen for most health systems in the second quarter of 2020 coinciding with onset of the COVID-19 pandemic (Figure, left panel). The weighted average BP control was 65.3% in 2019, dropped to 61.8% in 2020, and increased to 62.9% in 2021 and 62.6% in 2022. Similar patterns were observed for the improvement in BP metric (Figure, right panel): weighted average 31.4% in 2019, 25.7% in 2020, 29.1% in 2021 and 28.6% in 2022. Conclusion: BP control and improvement in BP decreased substantially during the COVID-19 pandemic. While both metrics improved after 2020, they were still below pre-pandemic levels through 2022. These findings underscore the importance of continued surveillance of BP control and other health impacts of the COVID-19 pandemic.

Background: Multiple myeloma (MM) is characterized by somatic mutations involving cancer-associated genes. The MyDRUG trial was initiated to explore the efficacy of specific molecularly-targeted therapies in combination with a standard triplet combination in MM. Methods: MyDRUG (NCT03732703) is a genomically-guided umbrella trial for patients with functional high-risk MM, defined as early relapse following primary therapy (3 years for transplant with maintenance, 18 months without), with specific genetic abnormalities. Patients with no actionable mutation or mutations with allelic burden below 30% were randomly assigned to one of the “non-actionable” arms. Here we present the data for the Y3 arm which combines selinexor (60mg po days 1,8,15), ixazomib (4mg po days 1,8,15), pomalidomide (3mg po days 1-21) and dexamethasone (40mg po weekly) (Seli-IPD), given on a 28-day cycle. The primary objective of the Y3 sub-protocol was to evaluate the overall response rate (ORR) according to the International Myeloma Working Group consensus criteria. Secondary objectives included assessment of adverse events (AEs). Results: 17 patients were enrolled into the Y3 arm. The average age was 62 (51-79), 65% were male with a median of 29 months since initial diagnosis and a median of 2 prior lines of therapy. The ORR (&gt; PR) was 52.9% with a clinical benefit rate (&gt; MR) of 58.8%. The median progression free survival was 10.2 months ( 95% CI: 3.9; 12.9) with a median overall survival which has not yet been reached; with all 17 patients still alive at the current data cutoff. No dose-limiting toxicities were seen. Eight patients (47.1%) experienced a serious AE with 2 patients (11.8%) experiencing an AE leading to treatment discontinuation. Two patients (11.8%) required dose reductions. The most common non-hematologic AEs were fatigue, nausea and constipation; all of which were grade 1 and 2. Conclusions: In this platform study of patients with relapsed, functionally high-risk MM, patients who received Seli-IPd exhibited significant efficacy and a manageable AE profile. Furthermore, this provides an all-oral option for patients wishing to minimize their office visits and parenteral therapy administrations.

Objective: We aimed to characterize seasonal variation in US population-based blood pressure (BP) control and BP-related metrics and evaluate the association between outdoor temperature and BP control variation. Methods: We queried electronic health records (EHRs) from 26 health systems, representing 21 states, to summarize BP metrics by quarters of 12-month periods from January 2017 to March 2020. Patients with at least one ambulatory visit during the measurement period and a hypertension diagnosis during the first 6 months or prior to the measurement period were included. Changes in BP control, BP improvement, medication intensification, average SBP reduction after medication intensification across quarters and association with outdoor temperature were analyzed using weighted generalized linear models with repeated measures. Results: Among 1 818 041 people with hypertension, the majority were more than 65 years of age (52.2%), female (52.1%), white non-Hispanic (69.8%) and had stage 1/2 hypertension (64.8%). Overall, BP control and process metrics were highest in quarters 2 and 3, and lowest in quarters 1 and 4. Quarter 2 had the highest percentage of improved BP (31.95 ± 0.90%) and average SBP reduction after medication intensification (16 ± 0.23 mmHg). Quarter 3 had the highest percentage of BP controlled (62.25 ± 2.55%) and lowest with medication intensification (9.73 ± 0.60%). Results were largely consistent in adjusted models. Average temperature was associated with BP control metrics in unadjusted models, but associations were attenuated following adjustment. Conclusion: In this large, national, EHR-based study, BP control and BP-related process metrics improved during spring/summer months, but outdoor temperature was not associated with performance following adjustment for potential confounders.