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Introduction: Teclistamab (Tec) is the first approved BCMA x CD3 bispecific antibody for the treatment of triple-class-exposed patients with relapsed/refractory multiple myeloma (RRMM) based on the pivotal MajesTEC-1 study. Tec was associated with high overall response rate (ORR) of 63% in heavily pretreated patients. After a longer follow-up of 30.4 months, CR rate was 46.1%, median duration of response (DOR) was 24 months (95% CI, 17.0 - not estimable), and median progression-free survival (PFS) was 11.4 months (95% CI, 8.8 - 16.4). Herein, we present updated analysis of real-world outcomes and safety with tec in RRMM with extended follow-up of more than 12 months. Methods: This is an international multicenter retrospective study of patients with RRMM treated with tec on-label at 9 academic centers from 5 countries (United States, United Kingdom, Greece, Spain, and Canada) through the International Myeloma Working Group (IMWG) Immunotherapy Committee. Patients with RRMM treated with commercial tec at the respective institutions between May 24, 2022 to January 4, 2024 were included. Median follow-up was 14 months with data collected until July 15, 2024. High-risk cytogenetic abnormalities (HRCA) was defined as 1q+, t(4;14), t(14;16), t(14;20), and/or del(17p). Response was assessed using the IMWG consensus criteria. Patient characteristics were summarized by frequency (percentage) or median (interquartile range [IQR] or range). PFS, overall survival (OS), DOR were evaluated using the Kaplan-Meier method. Results: There were 223 patients included in this analysis with the following characteristics: median age of 67 (range 33-91) with 24% ≥75 years; 45% female; 74% White, 10% Black, 9% Asian, and 7% other/unknown; 86 of 176 (49%) with high risk cytogenetics, including del(17p), t(4;14), t(14;16), t(14;20), and gain/amp 1q; 29.4% (37/126) with known extramedullary disease; 14% with creatinine clearance ≤30 ml/min. Patients received a median of 6 (IQR, 4-8) prior lines of therapy with 52% (107/206) being penta-drug refractory. Among 212 patients with available data, 161 (75.9%) patients would have been ineligible for MajesTEC-1. There were 94 (42%) patients who received prior BCMA-directed therapy (29.8% antibody-drug conjugate [ADC] alone; 45.7% CART alone; 6.3% bispecific antibody alone; 17.0% ADC and CART). Median time from diagnosis to tec initiation was 6.1 (range 0.6-29.2) years. For the 206 response-evaluable patients, ORR was 66%, including 25.2% ≥CR, 33.5% VGPR, and 7.3% PR. ORR for the 90 response-evaluable patients with prior BCMA-directed therapy was 54.5% (21.1% ≥CR, 26.7% VGPR, 6.7% PR). After a median follow-up of 14 (95%CI, 13-14) months, median PFS and OS were 8.8 (95% CI, 5.5-14) and 20 (95% CI, 18-not reached [NR]) months, respectively. 12-month PFS estimate was 46% (95% CI, 40%-54%), and 12-month OS rate was 65% (95% CI, 59%-72%). Median DOR was 17 (95% CI, 17-NR) months with 12-month estimate of 68% (95% CI, 60%-77%). Tec step-up dosing occurred in the outpatient setting for 57 (25.6%) patients. CRS occurred in 119 out of 222 (53.6%) patients with almost all being grade 1-2, except for 1 grade 4 event. ICANS occurred in 18 out of 216 (8.3%) patients (grade 1-2: 5.1%; grade 3-4: 2.8%). Any grade infection occurred in 130 (58.3%) patients; 25.1% of patients had grade ≥3 infection, including 10 patients with grade 5 infection. While receiving teclistamab, 79 (35.4%) patients had ≥2 infections. IVIG was given in 114 out of 164 (69.5%) patients. Conclusion: In this multicenter international real-world analysis of outcomes and safety associated with tec, ORR was high at 66% with 25.2% of patients achieving ≥CR. CR rates may be underestimated due to infrequent bone marrow confirmation in the real-world datasets. Encouragingly, ORR was 54.5% in BCMA exposed RRMM patients, including 21.1% with ≥CR. After a median follow-up of 14 months, heavily pretreated patients including patients with prior BCMA therapy had durable responses with median PFS of 8.8 months and median DOR of 17 months. There were no new safety signals noted in this real-world study. This is the largest real-world study to date of teclistamab with long-term follow-up of more than 12 months. Additional data including more patients, longer follow-up and results from difficult to treat subgroups will be presented at the meeting.

Introduction: Clonal hematopoiesis (CH) is a common age-related premalignant condition defined by the presence of an acquired somatic mutation in a gene frequently mutated in myeloid malignancies characterized by a variant allele frequency (VAF) of ≥2%, without fulfillment of other diagnostic criteria for myeloid neoplasm. Incidence of CH increases with age and found in 10%-30% of people > 70 years of age. CH-related mutations confer an increased risk of myeloid neoplasms, cardiovascular diseases, and are linked to inferior survival in solid tumor patients treated with chemo/radiation therapy. Such mutations can act as a driver/amplifier of inflammation, especially through myeloid cells. To distinguish true disease drivers from background genetic events related to aging or environmental factors, we need a deeper understanding of the impact of CH in different tissue microenvironments and under therapeutic pressure for better risk stratification of CH carrier patients. Recent reports suggested high prevalence of CH-related mutations in lymphoma. Current analyses aimed to investigate: i) the prevalence of CH-related mutations in two real-world lymphoma cohorts from Molecular Epidemiology Resource (MER) MER-FL and MER-DLBCL, ii) CH-related mutational landscape in DLBCL and FL, iii) the impact of CH-related mutations on clinical outcomes. Methods: Whole exome sequencing (WES) derived from blood/PBMC from lymphoma patients with paired tumor samples was analyzed to identify CH-related myeloid drivers in 42 previously reported genes. We used Sention-Tnhaplotype2 somatic pipeline with a custom panel of normals from whole blood samples. To avoid tumor contamination, we filtered variants for which VAF in the tumor was higher than that in the germline sample. Other filtering criteria included HIGH/MODERATE impact; read count > 1 in both forward and reverse reads; gnomAD_AF < 0.01. We used the R “survival” package Cox regression implementation for outcome and other statistical analysis. Results: Genomic and clinical data of 507 patients from MER-FL and 383 patients from MER-DLBCL cohorts, with median age of 60 and 64 respectively, were available for analysis. CH-related mutations were present in 17.16% (87/507) in FL and 18.28% (70/383) in DLBCL cohorts with a VAF cut off >2%. The most common CH-related mutations were DNMT3A (5%), CREBBP (2%), TET2 (1%), ASXL1 (1%) and PPM1D (1%) in MER-FL while DNMT3A (5%), TET2 (3%), TP53 (3%), ASXL1 (2%) and PPM1D (1%) in MER-DLBCL cohort. Both the prevalence of CH-related mutations and their average VAF increased with age, consistent with literature. Finally, cox regression analysis suggested that CH-related mutations were associated with significantly inferior overall survival (OS) in both FL and DLBCL cohorts (HR 1.6 p=0.028 and HR 2.3 p=<0.001 respectively); however only in DLBCL this association was significant after age correction (HR 1.8 p=0.008). When separated by individual gene mutations, genes of interest with inferior OS included TP53 (n=4, HR 3.1, p=0.057) in FL and PPM1D (n=3 HR 2.6 p=0.1), TP53 (n=8 HR 2.1 p=0.1) and DNMT3A (n=14, HR=2.0, p=0.048) in DLBCL; however, these estimates did not quite reach statistical significance. Conclusions: Taken together, our exploratory analysis indicates that CH-related mutations associate with worse OS in lymphoma patients, supporting the rationale for evaluation of CH for the risk assessment in lymphoma. Furthermore, DLBCL displays of larger size effect, which may be related to different treatment regimes. Additional studies will be needed to elucidate the interaction between high dose chemotherapy regimes and CH-associated adverse events.

Introduction: Talquetamab (Talq) is a GPRC5D targeting bispecific antibody recently approved for the treatment of relapsed refractory multiple myeloma (MM) based on the MonumenTAL-1 study. Real World Evidence (RWE) is needed to understand the safety and efficacy of Talq in patients treated outside of a clinical trial as they may have different outcomes and toxicities. Here we report outcomes of 118 patients treated with Talq. Methods: Patients treated with standard-of-care Talq were included. Data was collected through a retrospective chart review from 01/2023 until 7/2024 from 7 International Myeloma Foundation (IMF) associated MM academic centers. Results: 118 patients were included in the analysis. The median age was 64, 37% had HR disease, 22% had EMD at presentation. The median LOT was 6, median number of immunotherapies before TAL was 2 (range 1,4) and 71% received prior BCMA therapy. 72% were triple refractory and 44% were penta refractory. 25% (n=60) would not have been eligible for TAL clinical trial due to exclusion criteria and15% had an ECOG of 2 or greater. 18% (n=97) received TAL as an outpatient and the median number of hospital days was 9 (0,37) for inpatients. CRS during Step up Dose (SUD) 1 was present in 30% Gr 1 (57%), Gr2 (11%), Gr 3 (6%), CRS during SUD 2 was present in 31%, Gr 1 (65%), Gr 2 (11%), CRS during SUD 3 when administered was present in 14% , Gr 1 (82%), Gr 2 (6%) and with first full dose was 12% , Gr 1 (71%), unknown (29%). ICANS occurred in 6% (7/97), Gr 1 (14%), Gr 2 (29%), Gr 3 (14%) and unknown in 43% there was no evidence of HLH. Skin toxicity was present in 62% of patients (n=105/118) with 4% needing dose interruptions and presented as rash (20%), dryness (42%) and itching (20%). Nail toxicity was present in 20% (n=65/118), with 9% needing dose interruptions. Dysgeusia was present in 51% (n=97/118), with 10% needing dose interruptions. Oral toxicity manifest as stomatitis (10%), glossitis (1%), ulcerations (2%), dry mouth (27%), was present in 34% (n=61/118), with 12.5% needing dose interruptions. Infections were present in 34% (n=82/118) and CMV reactivation in 23% while only 1 patient needed treatment for CMV. The Overall Response Rate (ORR) was 64.9% with a VGPR rate or higher of 43.3% in this population. Updated efficacy data including PFS will be reported at the time of presentation Conclusions: This is the first largest RWE of the safety and efficacy of Talq in a heavily pretreated population with a high prior BCMA exposure. The ORR is consistent with a prior study by Jakubowiak et al which showed an ORR OF 65.7% after prior T cell engagers. The safety profile - CRS, ICANS, skin and oral toxicities was similar to the MonumenTAL study, CMV reactivation was higher and this may be related to treatment with prior immunotherapies and should be monitored in the future. This report shows that Talq has a similar safety and efficacy profile in the real world when sequenced after prior BCMA therapies.

Introduction: Diffuse large B cell lymphoma (DLBCL) patients experience favorable outcomes following frontline immunochemotherapy, however, 30-40% of patients will exhibit primary refractory disease or relapse (rrDLBCL). Recent studies have expanded upon well-defined characteristics of newly diagnosed DLBCL (ndDLBCL) to elucidate genomic landscapes underlying rrDLBCL; yet, high-throughput examination of resistance and relapse mechanisms within rrDLBCL subtypes, including the newly defined dark zone signature (DZsig) addition to cell of origin (COO), have yet to be described. To expand upon the current tumor etiology and define subtype-specific driving mechanisms, we describe a multi-omic analysis leveraging clinical and biologic variables in rrDLBCL. Methods: Tumor biopsies (N=228) collected at the time of relapse were obtained from n=85 participants in the Mayo Clinic/University of Iowa Lymphoma Molecular Epidemiology Resource (MER), n=73 in the Mayo Clinic Biobank, and n=38 from CC-122-DLBCL-001 or n=32 CC-122-ST-001 trials. Tumor samples were analyzed by WES (n=158) or WGS (n=70) and by RNAseq (n=145). Comparative analysis against ndDLBCL MER samples (N=444) utilized WES (n=404) and RNAseq (n=321). Chi Square or Fisher's exact test was used for enrichment analysis of categorical variables, while Wilcoxon or Kruskal-Wallis test was used for continuous variables. Results: rrDLBCL samples were enriched for ABC (46% vs 33% in ndDLBCL, p=0.01), and fewer GCB (27% vs 40%, p=0.006). Amongst rrDLBCL patients, variance in overall survival (from time of original diagnosis; log-rank p=0.001) was observed between COO subtypes, with poor outcomes in patients with DZsig (median 15.0 mo) and GCB (36.5 mo) compared to ABC tumors (74.4 mo). Patients with progression or relapse within 6 months featured a more even COO distribution (ABC - 22%, GCB - 34%, DZsig - 28%) than patients with early (6-24 mo; 51%, 22%, 22%) or late relapses (>24 mo; 62%, 19%, 4%), which were predominantly ABC. Comparing mutation frequency within subtypes, rrDLBCL GCB tumors were enriched for B2M (41% vs 15% in ndDLBCL, p=0.002), EP300 (19% vs 7%, p=0.059), CIITA (19% vs 5%, p=0.02), PRKCB (11% vs 2%, p=0.035), CD79B (11% vs 0%, p=0.004), and CD83 (8% vs 1%, p=0.049) mutations, and CNV events including gains at 8q24.21 (MYC locus; 48% vs 14%, p<0.001) and 18q21.33 (BCL2, TCF4 locus; 36% vs 15%, p=0.021), and losses at 17p13.1 (TP53 locus; 40% vs 19%, p=0.035). rrDLBCL DZsig tumors featured enrichment for BCL6 (22% vs 3%, p=0.025), and SPEN (17% vs 3%, p=0.062) mutations and 2q22.2 losses (LRP1B locus; 20% vs 0%, p=0.019). Despite differential mutation and CNV profiles, gene expression analysis revealed minimal variance within COO subtypes in rrDLBCL and ndDLBCL, however upregulation of lymphoma driving genes including MYBPC2 (LogFC=1.68, FDR<0.001), MYOM2 (LogFC=1.33, FDR=0.007), MYC (LogFC=0.61, FDR=0.04), and CELSR2 (LogFC=0.53, FDR=0.02) were observed in ABC rrDLBCL. Increased frequency of LymphGen classifier A53 was observed in ABC (43% vs 17%, p=0.005) and GCB (40% vs 14%, p=0.009) rrDLBCL. Using CIBERSORTx to infer lymphoma microenvironment (LME) cell type abundance, an LME-depleted class was evident in rrDLBCL tumors, including reduction of CD8+ T cells (effect size (r)=-0.78, p<0.001) and T follicular helper cells (r=-0.48, p=0.012) in GCB rrDLBCL and reduction of T follicular helper cells (r=-0.43, p=0.023) and Tregs (r=-0.32, p=0.065) in DZsig rrDLBCL. Significance: We present an update to the genomic landscape of rrDLBCL, highlighting GCB and DZsig tumors with differential biology and advanced clinical course. Our data supports increased implementation of sequencing efforts in rrDLBCL to more broadly evaluate relapse mechanisms, with optimism that a more detailed understanding of r/r disease may guide trials for targeted treatment strategies. For example, rrDLBCL patients may be strong candidates for MYC pathway targeting agents (BETi), or a Lenalidomide-based regimen (R2 or Tafa-Len), as Lenalidomide has been shown to reprogram the LME via PD-L1 expression in addition to downregulation of MYC and MYC target genes. Or, due to enrichment of variants affecting anti-apoptotic proteins including BCL6 or BCL2 in DZsig and GCB rrDLBCL, a venetoclax-based therapeutic may be considered. Further targeted strategies should be considered as development of a more personalized approach remains an unmet need.

Introduction: Hypereosinophilic syndrome (HES) is a group of rare diseases characterized by persistent hypereosinophilia in the blood and/or tissues, causing organ damage and dysfunction. This retrospective observational cohort study described the real-world disease burden and clinical characteristics of patients with idiopathic HES (I-HES) or lymphocytic HES (L-HES). Methods: Records of patients with I-HES or L-HES were collected from the TriNetX Linked Electronic Health Records (EHR) plus Claims Network, a database of de-identified EHR-derived data linked to closed claims data from healthcare organizations throughout the United States. Included patients had a first diagnostic record of HES (ICD-10-CM D72.11) between January 1st 2022 and September 12th 2023 and had continuous 12-month enrollment prior to their first HES diagnosis (index date), with gaps of up to 45 days permitted. Patients were excluded if they had myeloprolifertive or secondary reactive variant of HES, or an eosinophilic granulomatosis with polyangiitis diagnosis after their HES diagnosis. Baseline was defined as the 12-month period prior to the index date, and Year 1 was defined as the 12-month period after the index date. Analyses were descriptive. Results: At the index date, patients with I-HES or L-HES (N=53) had a mean (standard deviation [SD]) age of 41.6 (21.4) years, with nine (17.0%) patients aged less than 18 years, 15 (28.3%) of Black or African American race, and 27 (50.9%) of White race. The proportion of males was 60.4% (n=32). Prior to receiving an I-HES or L-HES diagnosis, 47.2% of patients either had an asthma diagnosis or were receiving inhaled corticosteroids or short-acting β2-agonist treatment but without a diagnosis of chronic obstructive pulmonary disease. Other common morbidities prior to I-HES/L-HES diagnosis were dorsalgia (28.3%), gastroesophageal reflux disease (20.8%), and hypertensive disease (20.8%). Amongst eosinophilic conditions, unspecified eosinophilia was recorded in 35.8% of patients and eczema was recorded in 18.9% of patients. In patients at baseline (N=53) and during Year 1 (n=19), the mean (SD) number of organ systems with HES signs and/or symptoms was 3.2 (2.3) and 2.7 (1.8), respectively. At baseline, 15.1% and 37.7% of patients had 3 or ≥4 organ systems, respectively, with I-HES or L-HES signs and/or symptoms; during Year 1, the proportion of patients with 3 or ≥4 organ systems with I-HES or L-HES signs and/or symptoms was 31.6% each. At baseline, I-HES and L-HES signs, symptoms and morbidities were most prevalent in the pulmonary system (60.4%), followed by the ears, nose and throat (41.5%), cardiovascular (35.8%), gastrointestinal (34.0%), cardiac (30.2%), and cutaneous (30.2%) systems. Compared with baseline, the proportion of patients during Year 1 with I-HES or L-HES signs, symptoms and morbidities was slightly higher for the pulmonary (63.2%) and cutaneous (36.8%) systems, and lower in the ears, nose and throat (36.8%), cardiovascular (31.6%), gastrointestinal (21.1%), and cardiac (26.3%) systems. Common I-HES and L-HES signs, symptoms and morbidities at the index date included: runny nose (34.0%), chest pain (32.1%), cough (32.1%), asthma (30.2%), dyspnea (28.3%), abdominal pain (24.5%), arthralgia (22.6%), eczema (18.9%), and heart palpitations (18.9%). Conclusion: I-HES and L-HES were associated with multiple morbidities and organ system involvement, indicating a high disease burden at the time of diagnosis. While I-HES and L-HES are primarily hematological disorders of hypereosinophilia, many other clinical specialties may diagnose and manage patients with these disorders.

Abstract Background The SUNSHINE and SUNRISE phase III trials demonstrated sustained clinical efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa (HS) through 52 weeks. Patients completing the core trials could enter a 4-year extension trial. Objectives To evaluate the long-term efficacy, safety/tolerability and maintenance of clinical response to secukinumab through week 104 in the extension trial. Methods Patients with a hidradenitis suppurativa (HS) clinical response (HiSCR) at week 52 of the core trials (extension trial baseline visit) entered a randomized withdrawal period. HiSCR responders receiving subcutaneous secukinumab 300 mg every 2 or 4 weeks (SECQ2W/SECQ4W) through week 52 in the core trials were randomized 2 : 1 to continue secukinumab (SECQ2W-R-Q2W or SECQ4W-R-Q4W) or receive placebo (SECQ2W-R-PBO or SECQ4W-R-PBO) through week 104. The primary endpoint was time to loss of response (LOR; newly defined for this trial) through week 104 in week 52 HiSCR responders (SECQ2W-R-Q2W vs. SECQ2W-R-PBO and SECQ4W-R-Q4W vs. SECQ4W-R-PBO). Time to LOR was tested at 1.25% (one-sided) for each comparison (one-sided familywise alpha of 2.5%) through week 104. If LOR was met, patients could remain in the trial on open-label secukinumab treatment. Additional endpoints included safety and HiSCR. The trial was registered with ClinicalTrials.gov (NCT04179175). Results Overall, 84.3% of patients who completed the core trials entered the extension trial; 55.9% were week 52 HiSCR responders. The primary endpoint was not met for either secukinumab dosing regimen. The estimated risk reduction for LOR was 13% (SECQ2W-R-Q2W vs. SECQ2W-R-PBO; one-sided P = 0.25) and 30% (SECQ4W-R-Q4W vs. SECQ4W-R-PBO; one-sided P = 0.04). The median time to LOR was numerically longer in the secukinumab arms vs. placebo {SECQ2W-R-Q2W [283 days; 95% confidence interval (CI) 176, –] vs. SECQ2W-R-PBO [239 days; 95% CI 120, –]; SECQ4W-R-Q4W [365 days 95% CI 225, –] vs. SECQ4W-R-PBO [171 days; 95% CI 113–337]}. In week 52 HiSCR responders reporting LOR, 44% (SECQ2W-R-Q2W), 58% (SECQ2W-R-PBO), 40% (SECQ4W-R-Q4W) and 34% (SECQ4W-R-PBO) were achieving HiSCR at the time of LOR. Overall, the safety of secukinumab was consistent with the core trials. Conclusions The primary endpoint of this trial was not met. HiSCR was maintained in many patients at the time of LOR. The safety of secukinumab was consistent with the previously characterized safety profile in the core trials.

Abstract Background Anal squamous cell carcinoma is a rare cancer with increased occurrence of multiple cancers before and after the anal squamous cell carcinoma diagnosis. However, there are limited data on this aspect. This multi-institutional analysis aimed to define the occurrence of malignancies before and after anal squamous cell carcinoma, time trends, and impact on survival and to identify prognostic factors. Methods Initial primary malignancy was defined as a malignancy occurring before the anal squamous cell carcinoma. Second primary malignancy was defined as a distinct primary cancer that developed after anal squamous cell carcinoma diagnosis. Retrospective multi-institutional chart review was done. Progression-free survival (PFS), overall survival, and prognostic factors were evaluated. Results A total of 647 patients with anal squamous cell carcinoma treated with curative intent were analyzed. Median age was 61.2 years with 72% as females. Of these, 150 (23.3%) patients had multiple malignancies with initial primary malignancy in 16% and second primary malignancy in 8%. Patients without prior cancer had better 5-year PFS (81.2% vs 67.2%, P = .011) and overall survival (81% vs 69%, P = .008) compared with those with prior cancer. Second primary malignancies had a statistically significant adverse impact on PFS (hazard ratio [HR] = 4.22) and overall survival (HR = 3.56). Females had better 5-year PFS (82% vs 70%, P = .016) as compared with males. The median time interval for developing anal squamous cell carcinoma (as second primary malignancy) after initial primary malignancy was 9.32 years. Conclusions Anal squamous cell carcinoma patients have an increased risk of multiple malignancies. These patients who have prior cancers have inferior outcomes. Second primary malignancy is a poor prognostic factor in patients with anal cancer. Second primary malignancy can develop years after treatment of primary anal squamous cell carcinoma.

Investment in physical space is a key strategic decision for healthcare managers. Understanding the current utilisation of clinical space is a significant input for this decision. Historically, direct observation or analysis of electronic health record (EHR) timestamps has been used to assess ambulatory space utilisation. Manual observation is prohibitively expensive, prospective and infeasible for large spaces. EHR data is limited to electronically captured workflows and to the quality of data capture. Two pilots explored the efficacy of real-time location systems (RTLS) to assess outpatient space utilisation to assist healthcare management professionals to make space allocation decisions. RTLS was shown to be viable, with accuracy that was not different from EHR-derived utilisation. RTLS had the following benefits: (a) more granular information, (b) data coverage in areas without EHR timestamps and (c) real-time assessment of utilisation. RTLS is an option for ambulatory care managers to understand the needed space for clinical operations.

INTRODUCTION: Gastroparesis is a debilitating gastroduodenal disorder for which gastric peroral endoscopic myotomy (GPOEM) has emerged as an efficacious treatment option. However, response to GPOEM varies between 50% and 80%, such that preoperative predictors of treatment success are needed to guide patient selection. METHODS: We performed a systematic review to identify predictors of clinical and functional response to GPOEM among adult patients with gastroparesis (PROSPERO: CRD42023457359). MEDLINE, Embase, and CENTRAL databases were searched systematically for studies reporting outcomes after GPOEM in September 2023. A narrative synthesis of predictive factors on univariable and multivariable analysis was performed with consideration of response rates through meta-analysis and evaluation of discrimination if prognostic models were developed. Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E) was used for risk of bias assessment. RESULTS: Of 1899 articles reviewed, 30 were included. The GPOEM response rate was 63.1% (95% confidence interval 56.3%–69.5%) with most studies defining clinical success on the basis of improvement in gastroparesis cardinal symptom index (87%, 26/30). Older age, shorter duration of gastroparesis, nondiabetic etiology, lower body mass index, and response to intrapyloric botulinum toxin were associated with positive response to GPOEM on multivariable analyses. Predictors on physiological tests such as EndoFLIP or gastric emptying scintigraphy were inconsistent. No prognostic models underwent external validation. DISCUSSION: Currently, there are limited reproducible predictors of response to GPOEM among patients with refractory gastroparesis. Robust prospective studies investigating scalable, reproducible, and actionable biomarkers of treatment response are required.