Foundation France. GK is a scientific co-founder of everImmune, Samsara Therapeutics and Therafast Bio. GK is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis and metabolic disorders.

An early discrimination of survival probability is required for patients with diffuse large B cell lymphoma (DLBCL), which may identify patients that require other treatment options, for example clinical trials. To the best of our knowledge, the impact of interim evaluation with 18fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has not yet been determined in this type of neoplasia. The aim of the present study was to determine the role of changes in metabolic tumor volume (MTV) between baseline and interim 18F-FDG PET/CT scans, following three courses of chemotherapy in order to predict complete response (CR) and overall survival (OS) in patients with DLBCL. Patients with previously untreated DLBCL who had received the standard 6–8 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone were included in the present study. A predictive model was constructed using changes in MTV and other clinical factors including age, gender, East Cooperative Oncology Group (ECOG) status, clinical stage, B symptoms, the presence of bulky disease and elevated lactate dehydrogenase levels, and data were analyzed using logistic regression analysis. In total, 50 patients with DLBCL were included in the present study. The majority of patients presented with stage III/IV disease (64%), B symptoms (72%) and bulky disease (58%). According to the International Prognostic Index score, 44% of patients were in the intermediate-high or high-risk categories for risk of relapse, and therefore considered to have poor prognosis. In total, ≥94% of patients achieving a decrease in total MTV had a 2-year OS rate of 95%, compared with the 58% OS rate of those with a suboptimal response. A multivariate model, including a change in MTV (a decrease of ≥94%), the ECOG performance status ≥2, a change in leukocyte counts and age, was used to predict CR. This model was used to define two groups according to the predicted probability of recurrence (cutoff, 0.69). The 2-year survival rates of the two groups were 95 and 59%, respectively. Analysis of changes in MTV in the interim 18F-FDG PET/CT revealed significant prognostic value for the prediction of CR and OS in patients with DLBCL.

The hypomethylating agents azacytidine and decitabine are unaffordable for many patients with MDS. The combination of the DNA methyltransferase inhibitor hydralazine and the histone deacetylase inhibitor valproate has shown preliminary efficacy in MDS. The aim of this study is to evaluate the clinical efficacy and safety of hydralazine/valproate in a case series of MDS patients treated in a compassionate manner. Hydralazine was dosed according to the acetylation genotype of patients (slow acetylators 83 mg daily; fast acetylators 182 mg daily), and valproate was dosed at 30 mg/kg/day. Both drugs were given daily until disease progression. Response and toxicity were evaluated with the International Working Group criteria and CTCAE, version 4, respectively. Survival parameters were estimated with the Kaplan-Meier method. From 2009 to 2012, 14 patients were treated. The median age ± SD was 55.2 ± 19.52 (range 23-87) years. According to the IPSS, cases were graded as intermediate-1 (n = 8/14; 57.2%) or intermediate-2 (n = 6/14; 42.8%). Responses were as follows: five (35.7%) complete response, one (7.1%) partial response, and two (14.28%) became transfusion independent. The mean duration of response ± SD was 60 ± 35.28 months (range 5-94). Three patients progressed to AML. At a median follow-up of 57 months (range 1-106), the median OS was 27 months. At that point, five patients remained on the treatment, one with partial response and four with complete response. The median OS was not reached in the eight patients who saw a clinical benefit from the treatment, in comparison to an OS of 7 months in the six patients who had no treatment. The combination of hydralazine and valproate is safe and effective in MDS, and its further testing is highly desirable.

9533 Background: The gut microbiome has been shown to be a biomarker of response in patients (pts) with melanoma. Strategies to modify the microbiome are currently being investigated. We report the effects of Fecal Microbiota Transplantation (FMT) on safety and anti-PD-1 response in pts with melanoma from a phase I trial (NCT03772899). Methods: 20 pts with advanced melanoma with RECIST-evaluable disease, without prior anti-PD-1 treatment for advanced disease, were recruited from 3 Canadian academic centers. Pts with ECOG > 2, autoimmune diseases, immunosuppression or unstable brain metastases were excluded. Pts received 80-100 g of healthy donor stool via oral capsules and were treated with anti-PD-1 one week later. The primary objective was safety of combining FMT with anti-PD-1 therapy. Objective response rate (ORR) by RECIST 1.1 and correlative studies were secondary objectives. Flow cytometry and multiplex ELISA were performed on pts blood samples. Avatar mice were transplanted with stool samples obtained from participants on the trial before and after FMT. Mice were subsequently implanted with B-16 or MCA-205 tumors and received anti-PD-1 antibodies. Results: Median age was 75.5 years, 12 (60%) were male, 18 (90%) had stage 4 disease, and 5 (25%) pts harbored a BRAF mutation. Median follow-up was 11.2 months. FMT-related adverse events included grade 2 diarrhea (2 pts) and hypophosphatemia (1 pt), and 13 pts (65%) experienced grade 1 gastrointestinal toxicities. Grade 3 immune-related adverse events (irAE) were one each of myocarditis, nephritis, and fatigue. Anti-PD-1 therapy was discontinued for toxicity in 2 (10%) pts. No unexpected irAE or death on treatment occurred. ORR was 65% (13/20), of which 3 were CR. Clinical benefit rate (includes SD lasting > 6 months) was 75% (15/20). Median PFS was not reached, and one pt died from their disease. Translational analyses demonstrated upregulation of IL-17 post-FMT in responders, which correlated with upregulation of the frequency of Th17 cells in peripheral blood. In parallel, murine experiments showed that feces from pts pre-FMT did not sensitize tumors to anti-PD-1. In both tumor models, only feces obtained post-FMT from responders restored anti-PD-1 efficacy in mice, providing strong support that FMT contributed to the anti-tumor response observed in pts. Conclusions: FMT followed by anti-PD-1 treatment in melanoma pts undergoing therapy is safe and may lead to improved anti-tumor responses that can be reproduced in tumor mouse models. The gut microbiome plays an important role in responses to anti-PD-1 in patients with advanced melanoma, paving the way for future microbiome-based interventions. Clinical trial information: NCT03772899.

The microbiome is now regarded as one of the hallmarks of cancer and several strategies to modify the gut microbiota to improve immune checkpoint inhibitor (ICI) activity are being evaluated in clinical trials. Preliminary data regarding the upper gastro-intestinal microbiota indicated that Helicobacter pylori seropositivity was associated with a negative prognosis in patients amenable to ICI. In 97 patients with advanced melanoma treated with ICI, we assessed the impact of H. pylori on outcomes and microbiome composition. We performed H. pylori serology and profiled the fecal microbiome with metagenomics sequencing. Among the 97 patients, 22% were H. pylori positive (Pos). H. pylori Pos patients had a significantly shorter overall survival ( p = .02 ) compared to H. pylori negative (Neg) patients. In addition, objective response rate and progression-free survival were decreased in H. pylori Pos patients. Metagenomics sequencing did not reveal any difference in diversity indexes between the H. pylori groups. At the taxa level, Eubacterium ventriosum, Mediterraneibacter (Ruminococcus) torques , and Dorea formicigenerans were increased in the H. pylori Pos group, while Alistipes finegoldii, Hungatella hathewayi and Blautia producta were over-represented in the H. pylori Neg group. In a second independent cohort of patients with NSCLC, diversity indexes were similar in both groups and Bacteroides xylanisolvens was increased in H. pylori Neg patients. Our results demonstrated that the negative impact of H. pylori on outcomes seem to be independent from the fecal microbiome composition. These findings warrant further validation and development of therapeutic strategies to eradicate H. pylori in immuno-oncology arena.