Citations

Abstract 9-ING-41 (elraglusib) is a potent and selective GSK-3 inhibitor that has shown anti-tumor activity in patient-derived xenograft models and phase1/2 clinical studies in patients (pts) with advanced solid tumors. Preclinical studies have demonstrated that elraglusib downregulates PD-1, TIGIT and LAG-3, upregulates expression of MHC class I proteins in tumor cells from “cold tumors”, and shows synergy when combined with PD-1 blockade in mouse xenografts. Clinical activity has been observed both as a single agent and in combination with standard of care chemotherapies in several advanced cancer histologies. Here we present initial ‘omics data from our phase 1/2 study (NCT03678883; ACT1801) spanning >100 pts with advanced cancer evaluating both single agent and chemotherapy combinations. The patients (pts) included in this study received elraglusib as a ≥3rd line therapy for advanced disease. Most pts with melanoma treated with elraglusib monotherapy (8/9; 89%) stayed on study for >2 cycles. One patient with melanoma refractory to checkpoint inhibitors achieved a confirmed and durable CR. Clinical benefit was also observed among pts with colorectal cancer with 4/12 (33.3%) pts treated with monotherapy and 12/15 (80%) that received elraglusib plus irinotecan rechallenge stayed on study >2 cycles reaching median overall survival of 106 and 211 days, respectively. Based on emerging in vivo and in vitro results demonstrating that elraglusib activates T and NK cells promoting anti-tumor immune responses, we hypothesize immunomodulation by elraglusib may be contributing to anti-tumor immune response in the 1801 trial. We have acquired TCRseq and RNAseq profiles of PBMC samples from seven patients in 1801 during the first two weeks of treatment with elraglusib monotherapy. In these pts, reduced TCR clonality was observed and specific TCR clonotypes expanded after treatment, indicating T cell activation and expansion. These pts also showed changes in PBMC populations during elraglusib therapy as measured by immune deconvolution of PBMC RNAseq. Taken together, these data support a novel, previously unrecognized immunomodulatory mechanism of action for elraglusib and could provide rationale for future clinical development of elraglusib in pts with advanced malignancies. Additional analysis from TCRseq, immune profiling and cytokine analysis from expanded cohort of pts is ongoing. Citation Format: Taylor Weiskittel, Joseph McDermott, Daniel Billadeau, Hu Li, Anwaar Saeed, Devalingam Mahalingam, Solmaz Sahebjam, Pamela Munster, Ludimila Cavalcante, Frank J. Giles, Andrew Mazar, Benedito Carneiro. Multimodal mechanism of action of the GSK-3 inhibitor 9-ING-41 (elraglusib) includes an immunomodulatory component: preliminary results from the 1801 phase 1/2 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT222.

The demand for genetic testing (GT) for prostate cancer (PCa) is expanding, but there is limited knowledge about the genetic counseling (GC) needs of men. A strong-to-moderate inherited genetic predisposition causes approximately 5–20% of prostate cancer (PCa). In men with prostate cancer, germline testing may benefit the patient by informing treatment options, and if a mutation is noticed, it may also guide screening for other cancers and have family implications for cascade genetic testing (testing of close relatives for the same germline mutation). Relatives with the same germline mutations may be eligible for early cancer detection strategies and preventive measures. Cascade family testing can be favorable for family members, but it is currently unutilized, and strategies to overcome obstacles like knowledge deficiency, family communication, lack of access to genetic services, and testing expenses are needed. In this review, we will look at the genetic factors that have been linked to prostate cancer, as well as the role of genetic counseling and testing in the early detection of advanced prostate cancer.

AbstractPlasmablastic lymphoma (PBL) is a rare entity, commonly associated with immunosuppressed states such as human immunodeficiency virus (HIV) infection or solid organ transplant. The clinical course is characterized by high relapse rates and a poor prognosis, leading some clinicians to recommend aggressive frontline therapy. However, a specific review of limited stage (LS) PBL patients is not available to evaluate outcomes and justify treatment recommendations. We performed a retrospective review of LS PBL cases to provide insight into this rare disease. Our cohort consisted of 80 stage I or II PBL patients from 13 US academic centers. With a median follow up of 34 months (1–196), the 3‐year progression‐free survival (PFS) and overall survival (OS) of the entire cohort were 72% (95% CI 62, 83) and 79% (95% CI 70, 89), respectively. The 3‐year PFS and OS of patients treated with frontline chemotherapy alone was 65% (95% CI 50, 84) and 71% (95% CI 56, 89), respectively, compared to 85% (95% CI 72, 100) and 96% (95% CI 89, 100), respectively, in patients treated with combined frontline chemotherapy with radiation consolidation. Our data demonstrate favorable outcomes in LS PBL with no improvements in outcome from aggressive frontline treatment including Hyper‐CVAD or auto‐SCT consolidation. Multivariate regression analysis (MRA) demonstrated improved PFS for patients receiving EPOCH based frontline therapy versus CHOP (HR: 0.23; p = 0.029). Frontline chemotherapy followed by radiation consolidation versus chemotherapy alone appeared to be associated with improved relapse and survival outcomes but did not show statistical significance in MRA.

BACKGROUND: Although the safety of laparoscopic redo ileocolonic resection for Crohn’s disease has been described before, the safety of robotic redo ileocolonic resection is still unelucidated. OBJECTIVE: This study aimed to share our preliminary experience regarding the safety of robotic redo ileocolonic resection for Crohn’s disease. DESIGN: Retrospective analysis. SETTING: Tertiary care center. PATIENTS: All consecutive adult patients who underwent robotic ileocolonic resection for Crohn’s disease at our institution between 2014 and 2021 were included. Patients were divided into redo ileocolonic resection and primary ileocolonic resection groups. PRIMARY OUTCOME MEASURES: Baseline demographics, preoperative risk factors, and intraoperative details were compared between both groups. The primary outcome was conversion to an open approach, and secondary outcomes were 30-day postoperative complications. RESULTS: A total of 98 patients were included. Of them, 18 (18.4%) had a redo ileocolonic resection. Patients who had a redo ileocolonic resection were more likely to have a longer duration of disease, associated anoperineal disease, a higher number of previous lines of medical treatments, received total parental nutrition before the operation for correction of malnutrition, and longer time for adhesiolysis. Patients who had redo ileocolonic resection had a higher risk for conversion to open ileocolonic resection [3 (16.7%) versus 2 (2.5%); p value = 0.04]. There was no statistically significant difference regarding the overall length of stay and the 30-day morbidity between both groups. No 30-day mortality or anastomotic leaks occurred in either group. LIMITATIONS: Retrospective nature of the analysis. CONCLUSIONS: Robotic redo ileocolonic resection showed similar short-term postoperative outcomes to robotic primary ileocolonic resection for Crohn’s disease. However, conversion rates are higher in robotic redo ileocolonic resection yet seem lower than previously published results in laparoscopic surgery. See Video Abstract at http://links.lww.com/DCR/C77. RESECCIÓN ILEOCÓLICA ROBÓTICA REDO PARA LA ENFERMEDAD DE CROHN: INFORME PRELIMINAR DE UN CENTRO DE ATENCIÓN TERCIARIA ANTECEDENTES: Si bien la seguridad de la resección ileocolónica laparoscópica para la enfermedad de Crohn se ha descrito antes, la seguridad de la resección ileocolónica robótica aún no se ha dilucidado. OBJETIVO: Este estudio tuvo como objetivo compartir nuestra experiencia preliminar con respecto a la seguridad de la resección ileocolónica robótica para la enfermedad de Crohn. DISEÑO: Análisis retrospectivo. AJUSTE: Centro de atención terciaria. PACIENTES: Se incluyeron todos los pacientes adultos consecutivos que se sometieron a resección ileocolónica robótica por enfermedad de Crohn en nuestra institución entre 2014 y 2021. Los pacientes se dividieron en grupos de resección ileocolónica reconfeccionada y resección ileocolónica primaria. MEDIDAS DE RESULTADO: Se compararon los datos demográficos iniciales, los factores de riesgo preoperatorios y los detalles intraoperatorios entre ambos grupos. El resultado primario fue la conversión a abierto y los resultados secundarios fueron las complicaciones posoperatorias a los treinta días. RESULTADOS: Se incluyeron un total de 98 pacientes. De ellos, 18 (18,4%) tuvieron resección ileocolónica. Los pacientes que se sometieron a una nueva resección ileocolónica tenían más probabilidades de tener una mayor duración de la enfermedad, enfermedad anoperineal asociada, un mayor número de líneas previas de tratamientos médicos, más probabilidades de haber recibido nutrición parental total antes de la operación para la corrección de la desnutrición y más tiempo tiempo de adhesiolisis. Los pacientes que se sometieron a una nueva resección ileocolónica tuvieron un mayor riesgo de conversión a cirugía abierta [3 (16,7 %) frente a 2 (2,5 %); valor p 0,04]. No hubo diferencia estadísticamente significativa con respecto a la duración total de la estancia y la morbilidad a los treinta días entre ambos grupos. No hubo mortalidad a los treinta días ni fugas anastomóticas en ninguno de los grupos. LIMITACIONES: Naturaleza retrospectiva del análisis. CONCLUSIÓN: La resección ileocolónica robótica mostró resultados postoperatorios a corto plazo similares a la resección ileocolónica primaria robótica para la enfermedad de Crohn. Sin embargo, las tasas de conversión son más altas en la resección ileocolónica robótica, pero parecen más bajas que los resultados publicados previamente en la cirugía laparoscópica. Consulte Video Resumen en http://links.lww.com/DCR/C77. (Traducción—Dr Yolanda Colorado)