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7029 Background: Mosun, a CD20xCD3 T-cell engaging bispecific antibody, is approved for relapsed/refractory follicular lymphoma after ≥2 prior lines of therapy. We report an interim analysis and PROs with Mosun SC in elderly/unfit patients with previously untreated DLBCL. Methods: MorningSun (NCT05207670) is a Phase 2, basket study of Mosun SC in patients with B-cell non-Hodgkin lymphoma. In the DLBCL cohort, eligible patients (aged ≥80 years, or 65–79 years and ineligible for chemoimmunotherapy) received outpatient Mosun SC: Day (D) 1 (5 mg), D8 (45 mg) and D15 (45 mg) of Cycle (C) 1, then 45 mg on D1 for up to 17 21-day cycles. Primary endpoint was progression-free survival (PFS) rate at 24 months. Other endpoints included overall survival (OS), objective response rate (ORR), complete response (CR) rate, change from baseline (CfB) in lymphoma symptoms as assessed by the Functional Assessment of Cancer Therapy-Lymphoma subscale (FACT-Lym LYMS; higher scores indicate improvement, a ≥3-point increase is considered clinically meaningful) and safety. Results: Forty-nine patients were enrolled, primarily from community sites (n=34). Median age was 83 years (range: 71–101). International Prognostic Index was 3–5 in 53.1% patients and 18.4% of patients had bulky disease. As of February 10, 2025, the median duration of follow-up was 12.5 months (range: 1.4–30.8). PFS and OS rates at 12 months were 71.3% (95% confidence interval [CI]: 54.8–82.7) and 74.7% (95% CI: 58.5–85.4), respectively. ORR was 73.5% and CR rate was 59.2%. Completion rates for FACT-Lym LYMS were ≥95% at baseline and remained ≥87% at each subsequent timepoint. Patients reported improvement in health-related quality of life (HRQoL) over time, demonstrated by increased mean CfB (standard deviation [SD]) in FACT-Lym LYMS scores: C4D1, 5.1 (9.8); C9D1, 5.6 (11.8); C17D1, 9.8 (11.4). Clinically meaningful improvements in lymphoma symptoms were observed in 53.1% (95% CI: 38.3–67.5) of patients. The most common any-grade adverse event (AE) was injection site reaction (53.1%; all Grade [Gr] 1/2). Gr 3/4 AEs were reported in 65.3% of patients and 8.2% experienced a Gr 5 AE (no Gr 5 AEs were Mosun related, per investigator assessment). Serious AEs occurred in 42.9% of patients. Infection AEs occurred in 49.0% of patients (Gr 1: 4.1%; Gr 2: 28.6%; Gr 3: 16.3%) and resolved in 91.7%. Cytokine release syndrome occurred in 12.2% of patients (Gr 1: 10.2%; Gr 2: 2.0%; all resolved). Updated data with around one additional year of follow-up will be presented. Conclusions: Mosun SC showed promising efficacy with manageable safety in elderly/unfit patients with previously untreated DLBCL in an outpatient setting. Clinically meaningful improvements in lymphoma symptoms suggest that Mosun SC improves aspects of HRQoL in this population. Clinical trial information: NCT05207670 .

5624 Background: Endometrial cancer (EC) is the most common gynecologic cancer and abnormal uterine bleeding (AUB) is the predominant presenting symptom. While <10% of AUB represents underlying EC, endometrial sampling is currently required to rule out EC. To develop an alternative, non-invasive rule-out strategy, we aimed to refine a previously reported EC-associated methylated DNA marker (MDM) panel in vaginal swabs. Methods: Patients ≥18 years old with AUB who met ACOG recommendations for endometrial sampling and those undergoing a hysterectomy for biopsy-proven EC or atypical hyperplasia (AH) were prospectively enrolled in a multicenter cohort study. A vaginal fluid specimen was collected via swab by a provider during a speculum exam. DNA was extracted from samples and bisulfite treated, followed by a target and signal amplification method to detect 8 previously identified MDMs. The cross-validated EC classification model used the mean of standardized MDMs. Clinical classification of benign endometrium (BE), EC, and AH was based on central pathology review. EC diagnoses were based on hysterectomy specimens. Endometrioid and mucinous constituted type 1 EC; serous, carcinosarcoma, clear cell, and mixed histology ECs were collectively analyzed as type 2. Results: Of 693 participants enrolled, 670 were evaluable with valid results: 524 in the AUB cohort and 146 in the suspected EC cohort. Within the AUB cohort, 16 had EC or AH. The final analysis cohort included 508 BE, 156 EC, and 6 AH. Of the evaluable participants 20% identified as Black, 3% Asian or Pacific Islander, 75% White, and 3% Other; 7% reported Hispanic ethnicity. Median age was 66 and 50 years for EC and BE AUB, respectively; 80% of those with EC and 43% with benign AUB reported being postmenopausal. Among participants with EC, 102 (65%), 17 (11%), 30 (19%), 6 (4%) were stage I, II, III, and IV, respectively; one EC was unstaged. Type 2 EC accounted for 42 (27%) of all EC cases. A 4-MDM panel yielded an AUC of 0.97 (0.96-0.99, 95% CI) for EC; models with 5-8 MDMs gave identical performance. All-stage EC sensitivity was 97, 97, 96, 95, and 92% at specificities ranging from 75, 80, 85, 90, and 95%, respectively. At the 85% (82-88%) specificity threshold, sensitivities across EC stage, type, and age were consistently high (Table). Sensitivity for AH was 33% (10-70%). Conclusions: An MDM panel demonstrated high sensitivity for EC across stage and EC type, supporting the potential for a non-invasive vaginal swab-based test to rule out EC. Future studies are necessary to finalize the panel and algorithm, prior to validating the test. Clinical trial information: NCT06294886 . EC Sensitivity (%, 95% CI) at 85% Specificity All Stages (n=156)* 96 (92-98) Stage I (n=102) 94 (88 - 97) II (n=17) 100 (82 - 100) III (n=30) 100 (89 - 100) IV (n=6) 100 (61 - 100) Type 1 (n=114) 95 (89 - 98) 2 (n=42) 100 (92 -100) Age ≤ 66 yrs (n=86) 95 (89 - 98) > 66 (n=70) 97 (90 - 99) *n=1 EC was un-staged.

536 Background: Folate receptor alpha (FRα) is overexpressed in ~80% of triple-negative breast cancers (TNBC). We previously demonstrated that patients (pts) with breast cancer naturally mount immune responses to FRα. In prior Phase I and II studies, a GM-CSF-adjuvanted FRα peptide vaccine (FRPV) was safe and induced durable FRα-specific T-cell immunity in 83–90% of pts with breast and ovarian cancer. Methods: Eligible pts were women ≥18 years with TNBC (ER/PR ≤10%) with 1+ of the following: stage ≥T1c disease, node-positivity, or residual disease after neoadjuvant chemotherapy. Pts were randomized 2:1 to receive FRPV or placebo (GM-CSF alone) every 28 days for cycles 2-7 and then every six months for 7 booster doses, with cycle 1 consisting of cyclophosphamide 50mg orally twice daily for days 1-7 and 15-21 (in both arms). Randomization was stratified by chemotherapy setting (adjuvant only vs neoadjuvant) and stage (I/II vs III). FRα expression was evaluated by immunohistochemistry. The study was designed to detect (at 30 months after the last pt enrolled) a disease-free survival (DFS) difference of 14% assuming a 3.5-year DFS rate of 70% in the control group and with 78% power. Results: 280 pts were enrolled (median age 52). The majority had stage I or II tumors (n = 219, 78%). There were numerically more node-positive tumors in the vaccine arm, 78 (41%) vs 27 (32%), p = 0.15. Median follow-up was 3.5 years, and 33 (FRPV: 25, placebo: 8) DFS events were observed; 3.5-year DFS rate was 88% with FRPV and 90% with placebo (HR 1.42, 95% CI 0.64–3.15; p = 0.39). Overall survival (OS) also did not differ by arm (HR 2.48, 95% CI 0.55–11.20; p = 0.22). Among node-positive pts (n = 105), DFS did not differ between arms (HR 0.95, 95% CI 0.34–2.66; p = 0.92). However, a numerical DFS event rate improvement (14% for vaccine vs. 26% for placebo) was observed in 61 patients with stage III disease (HR 0.51, 95% CI 0.16–1.68; p = 0.26). DFS did not differ by chemotherapy setting or by receipt of anthracycline, capecitabine, and/or an immune checkpoint inhibitor. FRPV was well tolerated, with predominantly grade 1–2 adverse events (AEs) and no vaccine-related grade ≥4 AEs. FRα expression was available from tumor in 230 pts, with 72% expressing > 0. Overall, DFS was not significantly associated with FRα expression (0 vs > 0; HR 0.55, 95% CI 0.21–1.44; p = 0.21), and no significant differences in DFS by FRα expression were observed between treatment arms. Conclusions: FRPV following oral cyclophosphamide was safe, with no vaccine-related high-grade AEs. While no significant improvement in DFS or OS was observed overall, a numeric trend toward improved DFS was observed in pts with stage III TNBC. This finding is hypothesis-generating and supports further evaluation of FRα-targeted vaccination in higher-risk TNBC. Immune correlative analyses are ongoing to better define vaccine immunogenicity and its relationship to clinical outcomes. Clinical trial information: W81XWH-15-1-0293.

4213 Background: Elraglusib (9-ING-41), a glycogen synthase kinase-3β (GSK-3β) inhibitor, has multimodal antitumor activity. In the international, open-label, randomized phase 2 1801 Part 3B study, elraglusib plus gemcitabine/nab-paclitaxel (GnP) was evaluated in previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC), with patients randomized 2:1 to weekly elraglusib/GnP or GnP alone. Primary endpoints were median overall survival (mOS) and 1-year survival. The GnP control arm demonstrated shorter mOS than contemporary randomized trials (7.2 months vs 9.2 months in NAPOLI-3 and 9.7 months in PASS-01), driven by higher early mortality (0–2 months: 23.1% vs 10.1% in NAPOLI-3). Given balanced randomization, similar early mortality was inferred in the elraglusib/GnP arm, prompting post-hoc analyses to contextualize efficacy and identify factors associated with early death. Methods: Efficacy and safety were summarized descriptively. Time-to-event endpoints were analyzed using Kaplan–Meier estimates, log-rank testing, and Cox proportional hazards models. Response rates were compared using the Cochran–Mantel–Haenszel test. Post-hoc subgroup, sensitivity, and machine-learning–based multivariate analyses explored clinical, demographic, and biomarker correlates of survival and early mortality. Results: In the full randomized population (elraglusib/GnP n=155; GnP n=78), elraglusib/GnP improved mOS by 2.9 months versus GnP (10.1 vs 7.2 months; HR 0.62; 95% CI 0.46–0.84; p=0.01), with 1-year survival rates of 44.1% versus 22.3%. Among patients receiving ≥1 full treatment cycle, mOS was 12.5 months with elraglusib/GnP and 8.5 months with GnP, comparable to contemporary registrational trials. Across multiple post-hoc sensitivity analyses—including evaluable patients, those matched to NAPOLI-3 baseline tumor burden, patients treated in the EU (early mortality 4%), and those achieving ≥20% CA19-9 decline within the first 1–2 cycles—elraglusib/GnP consistently demonstrated a ≥4-month OS advantage. Early death was associated with low baseline albumin (<3 g/dL), high CA19-9 (>800 U/mL), high tumor burden, and KRAS, TP53, and CDKN2A co-mutations. Conclusions: The elevated early mortality in the GnP control arm reflects enrollment of a heterogeneous, real-world mPDAC population with less restrictive eligibility than recent registrational trials. Post-hoc analyses identify key clinical and molecular drivers of early death and confirm a consistent survival benefit with elraglusib/GnP. These hypothesis-generating findings directly inform eligibility criteria, stratification, and endpoint assumptions for the planned phase 3 trial. Clinical trial information: NCT03678883 .

4122 Background: BTCs are rare and aggressive malignancies. The first-line standard of care regimen for advanced BTC (aBTC) is gemcitabine (GEM), cisplatin, and an immune checkpoint inhibitor. Although FOLFOX is a preferred second-line treatment, it is limited by neuropathy. Nal-IRI contains IRI free base in liposome nanoparticles, which shelter IRI from conversion to its active metabolite (SN-38) and increase intratumoral SN-38 compared with IRI alone. The NAPOLI-1 trial of FU/LV/nal-IRI vs. FU/LV in second-line advanced pancreatic adenocarcinoma showed an overall survival (OS) benefit. The NIFTY trial (South Korea) demonstrated median OS (mOS) benefit of FU/LV/nal-IRI over FU/LV in a second-line aBTC population (8.6 vs. 5.3 months [mo], HR 0.68, 95% CI 0.48-0.95); however, the NALIRICC trial (Germany) did not (6.9 vs. 8.2 mo, HR 1.08, 95% CI 0.68-1.72). We sought to characterize second-line FU/LV/nal-IRI efficacy in US patients (pts) with second-line aBTC. Methods: This was a single-arm, open-label, multicenter phase II study of pts with aBTC previously treated with GEM/platinum chemotherapy. Pts received nal-IRI 70 mg/m 2 IV over 90 minutes, LV 400 mg/m 2 IV over 30 minutes every 14 days, and FU 2400 mg/m 2 IV over 46 hours every 14 days. The primary objective was to determine progression-free survival rate at 4 mo (PFS 4mo ) using RECIST v. 1.1 criteria. Median PFS reported for pts receiving second-line 5-FU doublet chemotherapy was 3 mo with a PFS of 30%. FU/LV/nal-IRI was of interest if it could increase the PFS 4mo to 50% or higher. Using a one-sided α of 0.05 and 80% power, 17 of 39 evaluable pts had to be progression-free at 4 mo to detect a difference in PFS 4mo between 30% and 50%. Results: Forty-eight pts were enrolled: median age 64.5 years; 69% women; 27% gallbladder primary; 54% intra- and 19% extrahepatic. Ten pts came off study due to toxicity without disease progression before 4 mo on study and were replaced to evaluate the PFS 4mo endpoint. Of 38 evaluable pts, 18 pts (PFS 4mo 47%) were alive and progression-free at 4 mo, meeting the primary endpoint. With a median follow-up of 7.1 mo, median time to disease progression or study discontinuation due to toxicity for all pts was 2.3 mo (95% CI 1.8-4.6, PFS 4mo 38%), and for pts evaluable for the primary endpoint, median PFS was 3.5 mo (95% CI 1.8-5.5). Five pts (10%) had PFS beyond 12 mo. mOS for all pts was 7.9 mo (95% CI 5.7-11.7). Of 41 evaluable pts, the response rate was 2% (1 PR), and the disease control rate was 54%. Adverse events (AEs) were consistent with known toxicities from the FU/LV/nal-IRI regimen. Conclusions: FU/LV/nal-IRI is an effective second-line regimen for aBTC in US pts. There was significant early toxicity as 21% of pts came off study due to AEs before 4 mo. Correlative studies, including longitudinal analyses of circulating tumor DNA using banked blood specimens, are planned (NCT04005339). Clinical trial information: NCT04005339 .

4017 Background: First-line mCCA treatment is chemotherapy and immunotherapy. Based on the phase 2 FIGHT-202 trial, pemigatinib was the first FGFR1-3 inhibitor approved in second line and beyond for mCCA with FGFR2 rearrangement. Results from the phase 3, randomized, global FIGHT-302 trial evaluating pemigatinib as first-line therapy are reported here (NCT03656536). Methods: Patients (pts) aged ≥18 y with previously untreated mCCA with FGFR2 rearrangement were randomized 1:1 to receive oral pemigatinib (13.5 mg once daily q21) or intravenous chemotherapy (1000 mg/m 2 gemcitabine + 25 mg/m 2 cisplatin d1,8 q21 ≤8 cycles) stratified by previous receipt of 1 chemotherapy cycle, geographic region, and tumor burden. Pemigatinib crossover was allowed for control arm pts progressing on chemotherapy. Primary end point was progression-free survival (PFS). Secondary efficacy, safety, and exploratory end points were also analyzed. Results: After prescreening >4000 pts, only 196 had FGFR2 rearrangement and were screened; 167 were randomized to receive pemigatinib (n=83) or chemotherapy (n=84) before closing the study early due to slow accrual. Baseline characteristics and demographics were similar between arms. Median PFS (mPFS) with pemigatinib versus chemotherapy was 8.3 versus 6.8 mo, respectively (hazard ratio [95% CI], 0.58 [0.39-0.87]; nominal P =.0078); secondary efficacy endpoints generally supported primary results (Table). Median OS was similar, although these results are confounded by FGFR inhibitor administration as second-line treatment. In the crossover group (n=42, second-line pemigatinib), mPFS was 8.1 mo. Safety was consistent with previous results (Table). Exploratory analyses of genetic co-alterations associated with treatment response will be presented. Conclusions: FIGHT-302 was the first phase 3 trial of a targeted therapy for untreated mCCA. Pemigatinb demonstrated superior activity and prolonged mPFS compared with first-line chemotherapy. The results confirm the current management paradigm of pemigatinib administration after disease progression on chemotherapy. Clinical trial information: NCT03656536 . Pemigatinib Gemcitabine + cisplatin mPFS (95% CI), mo a 8.3 (6.5-12.2) 6.8 (6.1-8.3) Objective response rate, n/N (%) a 39/83 (47) 13/84 (15.5) Median duration of response (95% CI), mo a 14.2 (8.7-24.7) 6.3 (4.3-not estimable) Median overall survival (95% CI) a,b , mo 24.4 (18.6-35.9) 25.0 (18.7-34.2) Treatment related TEAEs, n/N c (%) 80/83 (96) 70/73 (96) Serious TEAEs, n/N (%) c,d 23/83 (28) 17/73 (23) Grade ≥3 TEAEs, n/N (%) c 65/83 (78) 49/73 (67) TEAEs leading to treatment discontinuation, n/N (%) c 5/83 (6) 8/73 (11) Fatal TEAE, n/N (%) c,d 3/83 (4) 0 a All randomized pts. b Interpretation limited by second-line treatment with FGFR inhibitor in gemcitabine + cisplatin arm. c Pts who received ≥1 study dose. d None deemed treatment related.

3109 Background: Poly(ADP-ribose) glycohydrolase (PARG) is an enzyme that catalyzes the removal of poly-ADP-ribose (PAR) chains from proteins during DNA damage repair. PARG inhibition leads to selective cell death in tumors with underlying replication fork defects, including BRCAm tumors, through a mechanism distinct from PARP inhibition. ETX-19477 is an oral, potent, and selective PARG inhibitor that shows robust preclinical activity in mouse models of ovarian, breast, and gastric cancers. Methods: ERADIC8 is an open-label, multicenter, Phase 1/2 study, consisting of two parts, dose escalation and dose expansion. A Bayesian Optimal Interval Design was used to enroll patients (pts) into dose escalation cohorts, with enrichment for pts with BRCAm high grade serous ovarian (HGSOC) and breast cancers. The primary objective is to assess safety/tolerability of ETX-19477 and define the maximum tolerated dose (MTD) and recommended Phase 2 dose(s). Secondary and exploratory objectives include pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity per RECIST v1.1. ETX-19477 is given orally once or twice daily in 21-day cycles. Results: As of Jan 6 2026, 45 pts were enrolled into the study across 11 dose levels (range: 80-750 mg QD, 190-350 mg BID). Tumor types included ovarian (n=24, BRCAm: 18), breast (n=8, BRCAm: 7), endometrial (n=6, BRCAm: 0), colorectal (CRC, n=3, BRCAm: 1), and other (n=4, BRCAm: 0) cancers. Treatment-related AEs (TRAEs; any grade) occurring in >20% of pts were nausea (53%), vomiting (38%), and fatigue (24%). The only Gr3 TRAE occurring in >5% of pts was neutropenia (16%). There was one Gr4 TRAE of neutropenia in 1 pt (2%) and no Gr5 TRAEs. ETX-19477 exposure is dose proportional, and the BID regimen achieves >85% PARG inhibition throughout the dosing interval in a blood-based PAR accumulation pharmacodynamic assay. As of the data cutoff, dose escalation is ongoing at 350 mg BID (MTD has not been defined) and dose expansion is ongoing at 200-300 mg BID. Among BRCAm, HGSOC pts enrolled at BID dose levels, there were 7 evaluable pts with a median of 4 prior lines of therapy (range 2–11): 2 pts achieved a partial response (PR, 29%) and 3 pts achieved stable disease (SD, 43%). Both pts with PRs were platinum-resistant and received prior PARP inhibitor treatment. 1 pt with BRCAm CRC remains on active therapy (250 mg BID) with SD for 7 months. Conclusions: ETX-19477 was well tolerated and showed anti-tumor activity in heavily pretreated pts with BRCAm, platinum-resistant HGSOC during dose escalation. These findings provide the first clinical proof-of-concept of PARG inhibition in HGSOC. ETX-19477 is being further evaluated in the dose expansion phase of the study. Clinical trial information: NCT06395519 .

2090 Background: A subset of meningiomas has an aggressive clinical course requiring multimodal therapies. Yet, treatment options beyond surgery and radiation are limited. Somatostatin receptor 2 (SSTR2) is uniformly expressed in meningiomas and can be targeted by the radiopharmaceutical agent [ 177 Lu]Lu-DOTA-TATE ( 177 Lu-Dotatate). [ 68 Ga]Ga-DOTA-TATE ( 68 Ga-Dotatate) PET is emerging as a promising imaging modality to assess treatment response in SSTR2-expressing tumors. However, prospective clinical data supporting the use of 177 Lu-Dotatate and 68 Ga-Dotatate in treatment-refractory meningiomas is limited. Methods: In this multicenter, open-label, phase 2 clinical study (NCT03971461), adult patients with progressive intracranial meningiomas received 177 Lu-Dotatate at 7.4 GBq (200 mCi) every 8 weeks for 4 doses. The primary endpoint was 6-month progression-free survival (PFS-6). Up to 5 meningioma lesions per patient were assessed by gadolinium-enhanced T1 MRI every 12 weeks. 68 Ga-Dotatate PET was obtained before/after 177 Lu-Dotatate treatments. Lesional 68 Ga-Dotatate PET activity was assessed relative to liver/spleen or superior sagittal sinus (SSS). Results: 32 patients (female = 21, male = 11) with progressive meningiomas (WHO grade 1 = 7, grade 2 = 24, grade 3 = 1) were enrolled. Median age was 65.5 (range 41-78) years. All patients had at least one prior tumor surgery and at least one course of radiation. Overall, 177 Lu-Dotatate was well tolerated and the most common grade 3/4 adverse events were transient cytopenia in 15 patients (47%). One patient (3%) discontinued treatment due to grade 4 thrombocytopenia. PFS-6 was reached in 22 patients (69%), which includes 5 of 7 (71%) with grade 1 and 17 of 24 (71%) with grade 2 meningiomas. Best radiographic response by MRI was partial response (PR) in 5 (16%) and stable disease (SD) in 20 (63%) patients. Eight patients (16 lesions) were evaluable by paired MRI and 68 Ga-Dotatate PET pre- and post-treatment. Referenced to SSS, 68 Ga-Dotatate avidity reduced by ≥50% in 2 lesions (PR), 25-49% (minor response, MR) in 3 lesions and remained stable ( < 25% reduction and < 25% increase) in 11 lesions. Using liver/spleen as a reference (6 patients, 14 lesions), 68 Ga-Dotatate uptake was reduced in 9 lesions and stable in 5 lesions. 68 Ga-Dotatate PET assessments were generally concordant with MRI-based treatment response assessments. Conclusions: The primary endpoint (PFS-6) was met in this phase 2 study with 69% of patients achieving PFS-6, thereby surpassing established historical benchmarks. 177 Lu-Dotatate was generally well tolerated and deserves further study in patients with advanced meningiomas. Exploratory 68 Ga-DOTATATE PET studies showed decreased uptake in a subset of lesions and bears promise as an imaging biomarker to assess treatment response. Clinical trial information: NCT03971461 .

Estimates of fibromyalgia prevalence vary widely worldwide due to differences in diagnostic criteria, study methodology, and population characteristics. Accurate estimates are essential to inform population-level surveillance, guide resource allocation, and highlight disparities in disease recognition and access to care. The objective of this systematic review and meta-analysis was to determine the global prevalence of fibromyalgia in the general population, and secondarily to identify factors moderating prevalence variation and to assess prevalence in defined at-risk subpopulations. Pooled prevalence estimates with 95% confidence intervals (CIs) were calculated using the inverse variance heterogeneity model with Freeman–Tukey transformation. Subgroup analyses were performed by sex, diagnostic criteria, country, and other study characteristics, and meta-regression assessed moderators including publication year and Human Development Index (HDI). Of 21,645 records identified, 1,728 underwent full-text review and 882 studies were included in the final analysis. Across 38 countries and 30,070,032 individuals (188 studies), the pooled fibromyalgia prevalence in the general population was 1.40% (95% CI, 0.49–2.47), with substantial heterogeneity (I 2 = 100%) and very low certainty of evidence. Among at-risk subpopulations (9,771,123 participants; 768 studies), prevalence was markedly higher in autoimmune and inflammatory conditions, such as chronic urticaria (37.1%), interstitial cystitis (30.8%), systemic sclerosis (20.6%), celiac disease (20.5%), and inflammatory bowel disease (19.9%), and elevated in chronic pain, rheumatologic, and post-infection cohorts. Meta-regression identified publication year (β = 0.008, P < .001) and HDI (β = 0.725, P = .002) as significant moderators of prevalence. In conclusion, fibromyalgia affects 1% to 2% of the global population, with substantially higher rates in at-risk subpopulations. Temporal and socioeconomic trends emphasize diagnostic inconsistency and global disparities in care.