Citations

Abstract Introduction: Epcoritamab (epco) and glofitamab (glofit) are bispecific antibodies (BsAbs) approved for the treatment of patients (pts) with multiply relapsed or refractory (r/r) large B-cell lymphoma (LBCL). Though response rates are relatively high, most patients (pts) eventually experience progression of disease (POD). We sought to investigate the treatment patterns and clinical outcomes following POD post-BsAb for r/r LBCL Pts, as this has not previously been described. Methods: We performed a multicenter retrospective study including 21 US centers evaluating pts with r/r LBCL receiving commercially available epco or glofit between 2023 and 2025. Baseline characteristics and outcomes were extracted from medical records. Efficacy and survival outcomes were assessed by site investigators and included overall response rate (ORR), complete and partial response (CR, PR) rates, progression-free survival (PFS) and overall survival (OS), analyzed using the Kaplan Meier method. Results: As of May 15, 2025, a total of 312 pts with r/r LBCLs were treated with BsAb, of whom a total of 168 (53.8%) pts experienced POD [104 of 193 (53.8%) treated with prior epco and 64 of 119 (53.8%) treated with prior glofit]. Pts with POD had a median age at BsAb start of 67 years (interquartile range [IQR] 58-76), most were male (68.4%), and the most common histology was diffuse large B-cell lymphoma not otherwise specified (n=122 [71.8%]). Sixty-seven of 168 pts (39.9%) with POD after BsAb had experienced primary refractory disease defined as failure to achieve PR or CR to frontline therapy. A total of 102 (60.7%) pts with POD to BsAb had received chimeric antigen receptor (CAR) T-cell therapy prior to BsAbs, with 33.3% of these pts being refractory to CAR T and 30.4% progressing within 6 months of CAR T-cell infusion. The median time to progression following BsAb start was 48 days. Following POD, 70 pts received no further anti-lymphoma therapy. Among 98 pts receiving subsequent therapy, 85 initially received systemic therapy and 13 initially received local therapy with radiation (concurrently with systemic therapy in 8 pts). The most commonly-used next line of systemic therapies included: loncastuximab tesirine in 19 pts (ORR 16.7%, all PR); commercial CAR T in 11 pts (ORR 50% [CR 36.4%, PR 18.2%); tafasitamab with lenalidomide in 7 (no responses); and other chemotherapy in 46 pts (ORR 27.6% [CR 24.1%]). The median follow-up time from POD was 9.2 months among survivors (95% confidence interval [CI] 7.8-13.3). Among those who initiated subsequent-line therapy following BsAbs, the median progression-free survival (PFS2) was 1.9 months (95% CI 1.5-2.4) and median overall survival (OS) from initiation of subsequent-line therapy was 3.9 months (95% CI 2.4-5.5). The estimated 1-year OS following initiation of next therapy was 12%. Conclusions: We report the outcomes of largest cohort of pts with POD post-BsAbs in r/r LBCL. Progression events occurred early after initiation of single agent BsAbs, and almost half of pts who progressed did not receive subsequent therapy. For those who received standard subsequent-line therapy after POD, response rates and survival outcomes were poor. Pts with POD after BsAB should be strongly considered for clinical trials of novel therapeutics or combination therapies.

Abstract Nucleophosmin mutations are among the most common aberrations in acute myeloid leukemia (AML). We previously uncovered a novel pivotal role for mutant NPM1 (NPM1c) in the nucleus, where it binds chromatin at key self-renewal gene loci, such as HOXA/B and MEIS1, directly regulating oncogenic transcription. How NPM1c regulates the transcriptional activity of its chromatin targets remains unclear. To identify potential nuclear cooperating partners of NPM1c, we employed TurboID proximity labeling of NPM1c and wild-type NPM1 (NPM1wt). Mass spectrometric analysis revealed an enrichment of nucleoporins in the NPM1c interactome, with Nucleoporin 98 (NUP98) emerging as a top candidate. NUP98, a key component of the nuclear pore complex (NPC), has been established as a critical oncogenic player in AML as part of oncogenic fusion proteins. In these oncofusions the N-terminal FG (phenylalanine-glycine) repeat domain of NUP98 is preserved and fused to a diverse set of partner genes. NUP98-fusion partners are believed to mediate the chromatin binding specificity of the oncoprotein while the NUP98 FG repeats have been shown to form biomolecular condensates that enhance transcriptional output. Interestingly, wild-type NUP98 (NUP98wt) itself has been linked to gene regulatory functions during embryonic development and normal hematopoiesis. However, the role of NUP98wt in transcriptional regulation in the context of leukemia remains unresolved. To explore a potential cooperation between NUP98wt and NPM1c we first validated their interaction by co-immunoprecipitation assays. We next wanted to determine whether NUP98 and NPM1c are recruited to the same chromatin sites. To this end, we performed ChIP-seq in an NPM1c endogenous degrader cell line. These experiments revealed co-occupancy of NUP98 at NPM1c target genes and a significant reduction of NUP98 binding upon degradation of NPM1c. These findings suggest that NPM1c is required for the recruitment of NUP98 to key oncogenic target loci. To dissect the functional role of NUP98wt in NPM1c AML, we performed loss of function studies. CRISPR mediated knock-out of NUP98 in NPM1 mutant (OCI-AML3) cells resulted in a significant repression of NPM1c target genes, including HOXA/B and MEIS1. Given the essential nature of NUP98, we also engineered an endogenous NUP98 degrader system in OCI-AML3 and NPM1wt (MV4-11) cells to allow for the study of the effects of rapid protein depletion. Upon degradation of NUP98, OCI-AML3 cells exhibited robust myeloid differentiation (~70% increase in CD11b) and increased apoptosis (~50% increase in Annexin V+). MV411 cells on the other hand did not show the same differentiation phenotype. To characterize the immediate transcriptional consequences of NUP98 depletion, we performed nascent RNAseq after 1 and 3 hours of degradation. In the first hours of degradation we observed a rapid and significant repression of NPM1c target genes such as HOXA/B cluster genes, MEIS1, SMC4, TNRC18, SATB1/2 and UNCX, thus demonstrating the strong dependency of the NPM1c-driven transcriptional program on the presence of NUP98. In contrast, in MV4-11 cells, NUP98 loss had no effect on HOXA/MEIS1 expression, suggesting a leukemia subtype-specific role of NUP98wt. To delineate the domains of NUP98 required for its chromatin function, we performed a CRISPR gene tiling screen of full-length NUP98 (635 sgRNAs) and based on this we generated several domain-deletion mutants for rescue experiments in the NUP98-degrader cell lines. Retroviral overexpression of the N-terminal FG-repeat containing domains of NUP98 was sufficient to rescue cell viability and prevent the differentiation phenotype typically observed upon NUP98 degradation. Strikingly, gene expression analysis showed that the NUP98 FG-repeats were sufficient to restore the expression of HOXA10, MEIS1, and HOXB9 expression. Overall, our study identifies NUP98wt as a critical cofactor for NPM1c-driven oncogenic transcription. NPM1c recruits NUP98 to its chromatin targets, functionally substituting for an oncogenic fusion partner to concentrate transcriptional condensates at oncogenic loci. This establishes a previously unrecognized, subtype-specific dependency on NUP98wt in leukemogenesis.

Abstract Introduction: CLL disease control and survival outcomes have improved since the introduction of Bruton tyrosine kinase inhibitors (BTKis). Since CLL often requires treatments, understanding patient preferences is critical in optimizing adherence and overall satisfaction. However, there are limited published data on how Korean patients prioritize treatment efficacy, safety and the convenience of administration. To address this gap, a discrete choice experiment (DCE) methodology was applied in a comprehensive quantitative analysis to evaluate patient preferences for BTKi treatment attributes among patients with CLL in Korea. Methods: Adult patients (≥18 years of age) with a confirmed diagnosis of CLL in Korea were recruited by The Korea Blood Disease & Cancer Association to participate in an online DCE survey questionnaire from April 30, 2025 to May 22, 2025. Treatment attributes and levels were identified based on published literature and clinical inputs. Efficacy attributes included progression-free survival (PFS); safety attributes included impacts of adverse events (AEs), including diarrhea, headache, atrial fibrillation and hypertension, on quality of life (QoL); convenience attributes included formulation type (including tablet or capsule) and dosing frequency (including once daily or twice daily). Preference data was analyzed using a conditional logistic regression. Relative importance of BTKi treatment attributes were calculated to measure the importance of each attribute in treatment decision-making. Additionally, subgroup analyses were conducted among patients aged <60 years and ≥60 years, those who received 2 or more lines (2L+) of treatments, and those who experienced AEs from CLL treatment. Results: A total of 57 patients completed the survey. The mean age was 61 years, with 46% aged <60 years and 54% aged ≥60 years. Female patients comprise 35% of the sample. Around 33% had a high school education or less, and 23% were employed full-time. More than half (54%) reported no comorbid conditions, and 70% were diagnosed ≥5 years ago (26% diagnosed 1 to <5 years ago; 4% diagnosed less than a year ago). In terms of treatment experience, 11% were treatment naive, while 89% received ≥1 treatment (61% first-line, 21% second-line and 7% third-line or later). In the context of CLL treatment preferences, patients showed a significant preference (P < .05) for therapies that minimized the impact of AEs on QoL, offered longer PFS, and required less frequent dosing. Formulation type did not have a statistically significant impact on treatment choice. Overall, patients placed greater importance on how treatment-related attributes affect their QoL and dosing frequency. The highest-ranked factors were the impact of headache (22%) and diarrhea (21%) on QoL, followed by dosing frequency (19%), the impact of atrial fibrillation (16%) and hypertension (14%) on QoL, PFS (7%), and formulation type (0.6%). Results from the subgroup analyses were generally consistent with the full sample analysis, with impacts of AEs on QoL being the most important factors for treatment decision-making, especially among older patients, although the relative ranking of impacts of AEs varied by age groups and treatment experience. Regarding efficacy, younger patients (<60 years of age) valued PFS slightly more than older patients (≥60 years of age), ranking it 4th and 6th out of the 10 attributes, respectively. Additionally, preference on dosing frequency was more important for 2L+ patients, reflecting the treatment burden experienced from previous regimens. Conclusions: This study provides valuable insights into the treatment preferences of Korean patients with CLL, highlighting the importance of QoL considerations for treatment decision-making. Among the evaluated attributes, patients placed the greatest weight on minimizing the impacts of AEs, particularly headache and diarrhea, on daily functioning, followed by dosing frequency. These preferences underscore the need for patient-centered care that prioritizes not only clinical efficacy but also tolerability and convenience. These insights can inform shared decision-making and support the development of personalized treatment strategies that better align with patient needs and expectations in Korea.

Abstract Introduction Approximately 40% of patients with DLBCL will experience relapse after initial treatment with standard-of-care chemo-immunotherapy. Effective treatment options are limited for patients who experience first-line treatment failure, particularly for those with R/R disease following CAR T-cell therapy or those not able to receive CAR T-cell therapy (Sehn et al, N Engl J Med. 2021). GOLCA is a potential, first-in-class, oral CELMoD agent designed for the treatment of lymphoma, with preferential distribution to lymphoid organs and enhanced activity in lymphoma cell lines. GOLCA drives the closed, active conformation of cereblon to induce rapid and deep degradation of Ikaros and Aiolos, leading to direct cell killing (agnostic of cell of origin) and immunomodulatory activity. In the two-part, multicenter, first-in-human Phase 1/2 study (CC-99282-NHL-001; NCT03930953), GOLCA was well tolerated and effective in patients with R/R DLBCL (Bachy et al, ICML 2025, #148). Here, we provide longer follow-up in patients with R/R DLBCL from Part B of the study. Methods Patients with R/R DLBCL and disease progression after ≥ 2 lines of therapy or transplant-ineligible patients after ≥ 1 line of therapy were included in the study. Patients received GOLCA monotherapy orally, once daily at different dosing schedules in Part A. In Part B, GOLCA was dosed at 0.2 or 0.4 mg (14 days on/14 days off) ± R. Total GOLCA treatment duration was up to 2 years or until progressive disease (PD)/unacceptable toxicity. Primary objectives included safety and recommended Phase 2 dose determination. Results As of April 3, 2025, a total of 77 patients with R/R DLBCL were enrolled in Part B Cohort C (GOLCA 0.2 mg + R, n = 39; GOLCA 0.4 mg + R, n = 38). Median age was 66 years (range, 20–86). Patients were heavily pre-treated; median number of prior treatments was 4 (range, 1–11), 55% of pts had prior CAR T-cell therapy, 38% had prior bispecific antibody treatment, and 44% were refractory to last treatment. Ten patients (13%) were ongoing, 4 completed 2 y of treatment, and 63 (82%) had discontinued treatment, mostly due to PD (n = 48 [62%]). The most common any-grade (G) treatment-emergent adverse events (AEs) in the 0.2- and 0.4-mg cohorts, respectively, were neutropenia (54% and 84%), an on-target side effect of GOLCA, and anemia (44% and 45%). G3/4 neutropenia was reported in 49% of patients with 0.2 mg and 79% with 0.4 mg, and febrile neutropenia (FN) in 5% and 16%, respectively. Granulocyte colony-stimulating factor was used in 81% and 88% of patients with neutropenia and 50% and 100% of patients with FN in the 0.2-mg and 0.4-mg cohorts. Dose interruptions (mainly due to infections/neutropenia) occurred in 49% and 53% of patients and discontinuations due to AEs occurred in 10% and 3% with 0.2 and 0.4 mg. One G5 pneumonia was considered related to study treatment (0.2 mg). The median follow-up was 11.8 months (range, 3.1–35.1) with 0.2 mg and 16.2 months (range, 3.8–31.4) with 0.4 mg. The overall response rate (ORR) in efficacy evaluable patients was 34% (complete response rate [CRR], 20%) with 0.2 mg (n = 35) and 58% with 0.4 mg (n = 36), including a CRR of 44% with this dose. In patients with prior T-cell–redirecting treatment, the ORR was 33% (CRR, 22%) with 0.2 mg (n = 18) and 56% (CRR, 38%) with 0.4 mg (n = 16). Seven of 35 (0.2 mg) and 14 of 36 (0.4 mg) patients experienced durable response > 12 months. The median time to response with both 0.2 and 0.4 mg was 1.8 months. In patients with durable responses (remained in response [CR or partial response] for more than two consecutive efficacy assessments) to GOLCA, circulating tumor DNA reduction from baseline continues to deepen over time. Response was similar across clones/tumor variants. Conclusions With additional follow-up, GOLCA + R continued to demonstrate a predictable and manageable safety profile, with no new safety signals observed at longer follow-up. Durable responses were shown in heavily pretreated patients with R/R DLBCL, including those with prior T-cell–redirecting therapy. GOLCA + R induced a decrease in circulating tumor DNA across tumor variants. These data support the ongoing development of GOLCA + R in patients with R/R non-Hodgkin lymphoma.

Abstract Introduction: Epcoritamab (epco) and glofitamab (glofit) are bispecific antibodies (BsAbs) approved for the treatment of patients (pts) with relapsed or refractory (r/r) large B-cell lymphomas (LBCLs). Their use is associated with relatively high response rates, with some patients experiencing prolonged remission. It is unclear whether continuous treatment beyond 12 months for pts in remission is beneficial, as continued immunosuppression may result in additional toxicity. We sought to report the outcomes of pts with prolonged remission and survival following BsAb administration. Methods: We performed a multicenter retrospective study including 21 US centers evaluating pts with r/r LBCLs receiving commercially available epco or glofit between 2023 and 2025. Baseline characteristics and outcomes were extracted from medical records. Efficacy and survival outcomes were assessed by site investigators and included overall response rate (ORR), complete and partial response (CR, PR) rates. Pts who responded to BsAbs and had ≥365 days of follow-up from initiation of BsAb treatment were included in the analysis. Results: As of May 15, 2025, a total of 312 pts with r/r LBCLs were treated with BsAbs (epco n=193, glofit n=119) with a median age of 66 years (interquartile range [IQR] 59-73) at BsAb start. Most were male (64.5%), had advanced stage disease (77.4%) and had ECOG performance status of ≤1 (93.3%) at BsAb start. Of 207 pts who had initiated treatment with BsAb ≥12 months prior to data cutoff, we identified 31 pts (15.0%) who had a response to BsAbs (19 epco, 12 glofit) and were alive without progression at 12-months post-BsAb initiation and included them in this landmark analysis. Of the cohort of 19 pts treated with epco, 6 discontinued due to reasons other than disease progression including CAR-T cell therapy (n=2), secondary malignancy (n=2), allogeneic transplant (n=1), or other reasons (n=1). Thirteen of 19 pts received ≥12 months of epco treatment, and, with a median follow-up of 16 months from the start of BsAb, 12 of 13 pts continued receiving epco beyond 12 months with one pt discontinuing after 12 months (observed for an additional 41 days prior to censoring). Of the cohort of 12 pts treated with glofit, 8 pts were observed after completing all planned therapy and 4 patients underwent allogeneic transplant. Among all 31 BsAb-treated patients alive and in remission at 12 months, at the time of data cutoff, 5 pts (12.9%) had progressed (2 previously treated with epco and 3 with glofit). Three of the 4 pts who underwent allogeneic transplant after prior glofit treatment experienced disease relapse. A total of 24 pts (77.4%) were alive at the time of last follow-up, with the causes of death being disease progression (n=1), secondary malignancy (n=1), infection (n=1), and unknown cause (n=4). Conclusions: In this large cohort of r/r LBCL pts treated with BsAbs monotherapy in the standard of care setting, a relatively small proportion of pts (15%) achieve the 12 month PFS landmark. In the absence of robust evidence for what constitutes best practice, different strategies are employed, including continuation of BsAb, observation as well as consolidation with allogeneic transplant or CAR T-cell therapy. Additional follow-up will be reported to help guide clinical decision making regarding the optimal management strategy for this high risk pt population.

Abstract Introduction: Bruton tyrosine kinase inhibitors (BTKis) have transformed the treatment landscape for CLL, offering significant improvement in patient outcomes. Despite the widespread adoption of BTKis and their proven clinical benefits, data on the treatment preferences and priorities of patients with CLL in Asia, particularly in Japan, are limited. Understanding patient preference is critical for optimizing clinical decision-making and tailoring treatment strategies for Japanese patients. A comprehensive quantitative analysis was conducted to evaluate patient preferences for covalent BTKi treatment attributes and trade-offs among these attributes. Methods: An online survey applying discrete choice experiment (DCE) methodology was administered between April 29 and June 30, 2025 to Japanese adults (≥18 years of year) diagnosed with CLL. The design of DCE attributes and levels was informed by literature review and clinical consultations. Treatment attributes included efficacy (i.e., progression-free survival [PFS]), safety (i.e., impacts of diarrhea, headache, atrial fibrillation, and hypertension on quality of life [QoL]), and convenience (i.e., formulation type including tablet or capsule, and dosing frequency including once daily or twice daily). A conditional logistic regression was applied to estimate preference weights, which were used to calculate the relative importance as well as willingness-to-tradeoff between BTKi treatment attributes. Results: The study included 50 patients (mean age: 62 years; 30% female; 38% employed full-time; 60% reported no comorbid conditions). More than half (60%) were diagnosed ≥5 years ago. Around one quarter (24%) were treatment naive, and 76% received ≥1 treatment (40% first-line, 26% second-line and 10% third-line or later). Most patients (82%) reported living with or near their caregiver. In terms of travel time to obtain CLL medication, 46% reported travel time of one hour, 40% traveled less than 30 minutes, and 14% traveled more than two hours. The majority of patients (66%) were using High-Cost Medical Expense Benefit, while an additional 10% were either currently applying or planning to apply. In general, patients preferred treatments with less impact of AEs on QoL, higher efficacy, and less dosing frequency (P<.05). The top three treatment attributes with the highest relative importance were the impact of atrial fibrillation (24.7%) and diarrhea (21.0%) on QoL, and PFS (15.8%), followed by impact of headache (15.7%) and hypertension (14.1%) on QoL, dosing frequency (7.8%), and formulation type (capsule or tablet) (0.9%). Patients were willing to trade off PFS for improved quality of life: accepting reductions of 3.1 years for less impact from atrial fibrillation, 2.7 years for diarrhea, 2.0 years for headache, and 1.8 years for hypertension (none or mild vs. significant impact). Additionally, they were willing to accept a reduction of 1.0 years of PFS to receive a treatment given once daily rather than twice daily.Conclusions: This is the first quantitative assessment of treatment preferences among Japanese patients with CLL using a DCE approach. Findings from this study provide valuable Japan-specific insights, highlighting that although efficacy is important, patients prioritize safety factors, such as the impact of atrial fibrillation and diarrhea on QoL. These findings support the integration of patient perspectives into treatment planning to enhance shared decision-making, personalize care, and promote better adherence to long-term therapies in CLL management.

Introduction Registrational trials are clinical trials which are used to justify regulatory approval of a new medication by the FDA. However, clinical trials may not be designed around patient-centred outcomes, like overall survival (OS) or quality of life. This disconnect raises concerns about whether current trial designs are truly aligned with the long-term needs and priorities of patients. A comprehensive analysis of trial designs and endpoints is necessary to ensure that future oncological therapies deliver meaningful clinical improvements. Our objective was to describe types of clinical trial design and primary endpoints used for registrational trials, and their trends over time. Research design and methods In this cohort study, the HemOnc database was used to identify registrational trials supporting cancer drug approval from 2004 through 2023. Clinical trial design (escalation, de-escalation, in-class switch, out-of-class switch) and primary endpoint (OS; time-to-event including progression-free survival; response-based endpoint) were characterized. Results Escalation trial designs were more common than in-class switches or out-of-class switches. De-escalation and mixed designs were exceedingly rare. The most common primary endpoint was a composite time-to-event endpoint. Conclusion Most clinical trials leading to FDA approval for cancer-directed therapies employ escalation designs with composite time-to-event endpoints. Designs reflecting paradigm shifts in therapy (in-class switches and out-of-class switches) are sparsely used. This approach raises the concern that trials may increase therapeutic toxicity without delivering meaningful improvements in OS or quality of life.

OBJECTIVE Objective values on procedural risk are essential to facilitate informed consent and optimize clinical decision-making in patients with unruptured intracranial aneurysms (UIAs). While robust heuristics, such as the PHASES (population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage, and site of aneurysm) score, are established for predicting rupture risk, contemporary and granular benchmarks for procedural safety remain scarce. The multinational Prediction of Adverse Events After Microsurgery for Intracranial Unruptured Aneurysms (PRAEMIUM) study aims to comprehensively characterize contemporary adverse event rates following microsurgical treatment at high-volume expert centers, stratified by aneurysm location, morphology, and complexity factors to better inform individual risk/benefit analyses. METHODS A cohort study among 20 participating expert centers from 9 countries was established. Patients treated microsurgically for UIAs were included. The authors describe the epidemiology of treated patients and UIAs and a comprehensive adverse event profile using 3 outcomes measured at hospital discharge: 1) poor neurological outcome (modified Rankin Scale score ≥ 3), 2) new sensorimotor neurological deficits, and 3) all-cause adverse events (Clavien-Dindo grade ≥ 1). Subgroup reports were given for aneurysm location, morphology, and complexity factors (prior aneurysm treatment, calcifications, complex angioanatomy involving critical branch vessels or perforators, and thrombosis). The authors purposely chose discharge as the time point to capture early postoperative risks and complications in patients with asymptomatic UIAs, for whom preserving neurological function is paramount. RESULTS The cohort included 3705 patients (mean age 56 [SD 12] years, 28% male). Overall, at discharge 13.9% of patients (95% CI 12.8%–15.0%) had poor neurological functional outcomes, 14.4% (95% CI 13.3%–15.5%) had new sensorimotor deficits, and 24.1% (95% CI 22.8%–25.5%) experienced all-cause adverse events. Poor neurological outcomes ranged from 8.5% (M1 aneurysms) to 37.4% (posterior circulation aneurysms), neurological deficits from 9.3% (distal anterior cerebral artery [ACA] aneurysms) to 34.2% (posterior circulation aneurysms), and all-cause adverse events from 21.2% (distal ACA aneurysms) to 31.3% (posterior circulation aneurysms). Dissecting and fusiform aneurysms showed notably high rates of poor neurological outcomes (22.0%–33.3%), new deficits (25.4%–26.7%), and adverse events (26.7%–37.0%). Complexity factors significantly influenced outcomes, with prior treatment (22.9%, 19.7%, and 30.1%), calcification (16.3%, 18.1%, and 30.5%), complex angioanatomy (13.1%, 15.9%, and 26.9%), and thrombosis (19.6%, 23.9%, and 39.6%) notably increasing the risks for poor neurological outcomes, deficits, and adverse events, respectively. CONCLUSIONS This large international cohort provides contemporary benchmarks for microsurgical treatment of UIAs, emphasizing variability in outcomes based on aneurysm location, morphology, and complexity. The presented granular and quotable adverse event rates support informed patient counseling and individualized risk/benefit assessments in comparable high-volume centers.

Abstract Purpose: Colorectal Cancer (CRC) is a leading cause of death from cancer globally. Surgery is the mainstay of treatment for localized CRC; however, little is known about survival outcomes following CRC surgery in low- and middle-income countries (LMICs). In this study, we examine the published literature for data on long-term outcomes following CRC resections in LMICs. Methods: We systematically reviewed PubMed, Web of Science, Embase, and Global Index Medicus for original research articles reporting survival data after CRC resection with curative intent in LMICs, published between January 2005 and May 2022. LMICs were defined according to the 2020 World Bank categories. We excluded studies without English full text or involving pediatric populations (<18 years), non-primary colorectal, benign disease, and endoscopic/transanal resection only. Studies from China dominated the published literature and were excluded. Abstracts and full texts were reviewed by two independent reviewers, and a third reviewer resolved conflicts. Disease-free survival (DFS) and overall survival (OS) data were extracted, and random effects modelling was used to estimate the pooled survival rates. Results: Our search returned 32,261 articles. After deduplication, 20,729 abstracts were assessed for eligibility, with 154 articles meeting inclusion criteria, representing a total of 20,589 CRC patients. 98 (63.6%) studies were from upper-middle-income (UM) countries, 55 (35.7%) from lower-middle-income (LM) countries and only one was from a low-income (L) country. Notably, only 27 (20%) of the 137 LMICs were represented in the literature. Turkey accounted for the highest frequency (29%) of included articles. Most (60%) of the studies were retrospective cohort design, and only three (3) were randomized controlled trials. The pooled 5-year OS estimate was 88% (95% CI: 77–95) for Stage I disease, 76% (69–81) for Stage II, and 57% (49–64) for Stage III. 5-year DFS estimates were 82% (71–90), 76% (67–84), and 59% (51–65) for stages I, II and III respectively. Survival rates varied considerably between income groups, with the strongest disparity seen with Stage III OS data at 18 months: 89% in UM, 86% in LM, and 50% in L (p=0.0005). Conclusion: With the rising incidence of CRC in LMICs, our work highlights the dearth of data on long-term outcomes following CRC operations in LMICs and emphasizes the urgent need for research capacity building, especially in low-income countries. Citation Format: Oluwasegun Afolaranmi, Thomas M. Diehl, Sehar Salim Virani, Qiuyu Yang, Kenechukwu Okwunze, Adel H. Khan, Nabiha Akhlaq Mughal, Daniel Schroeder, Sheida Pourdashti, Leslie Christensen, Sadaf Khan, Syed Nabeel Zafar. Survival Following Colorectal Cancer Surgery in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis [abstract]. In: Proceedings of the 13th Annual Symposium on Global Cancer Research; 2025 Sep 16. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(12_Suppl):Abstract nr 84.