Progression and hyperprogression after anti-PD1 therapy for unresectable stage III or IV melanoma patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21021-e21021
Author(s):  
Elise Colle ◽  
Stéphane Dalle ◽  
Laurent Mortier ◽  
Bernard Guillot ◽  
Caroline Dutriaux ◽  
...  
Keyword(s):  
Survival Rates ◽  
Real Life ◽  
Advanced Melanoma ◽  
First Line ◽  
Best Response ◽  
Unresectable Stage ◽  
Group A ◽  
Similar Survival ◽  
Group B ◽  
Response Group

e21021 Background: Primary progression (PP) and secondary progression (SP) to anti-PD1 therapy (APD) are poorly described in advanced melanoma in real life practice. Hyperprogression with a deleterious effect is reported in many cancers but is poorly assessed in advanced melanoma. Methods: Characteristics of 793 patients treated by APD (nivolumab or pembrolizumab) between July 2014 and May 2018 were collected from MelBase, a prospective French biobank (NCT02828202).We considered: group A (progressive disease as best response), group AHP (hyperprogression) within group A patients (progression/death within 3 months with normal initial LDH and ECOG at baseline, and either ECOG increased from 0 to 3-4, either LDH increased from normal to elevated or both), group B SP (response or stable disease then progression). Characteristics for all and survival for patients alive at progression (AAP) were also described. Results: Median follow-up was 11.3 months (Q1-Q3 4.8–23.6). Characteristics at baseline are in the table. In group A, 14% patients died at progression; within 262 patients AAP, 17% continue APD (the same or switch), 15.1% (CI95 11.1-20.6) were alive 1-year after progression (1YAP); 20.5% for patients in first line and 11.5% for pretreated. In group AHP, 41% patients died at progression; within 48 patients AAP, 12% continue APD, 11.1% (CI95 7.8-13.6) were alive 1YAP. In group B, 11% patients died at progression; within 88 patients AAP, 36% continue APD, 10.3% (CI95 5.2-20.1) were alive 1YAP, 15.9% for patients in first line and 7.0% for pre-treated. Conclusions: Our study shows that PP and SP to APD differ at baseline, but have similar survival rates at progression, while mechanisms involved might be different, providing important landmarks to build second line trials. This study thus highlights the existence of hyperprogressors among which 41% patients died within 3 months, as well as describes their associated characteristics. [Table: see text]

scholarly journals Effectiveness and safety of secukinumab in 608 patients with psoriatic arthritis in real life: a 24-month prospective, multicentre study

RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001519
Author(s):  
Roberta Ramonda ◽  
Mariagrazia Lorenzin ◽  
Antonio Carriero ◽  
Maria Sole Chimenti ◽  
Raffaele Scarpa ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Adverse Events ◽  
Disease Activity ◽  
Biological Treatment ◽  
Retention Rate ◽  
Real Life ◽  
Drug Retention ◽  
Group A ◽  
Group B ◽  
Drug Retention Rate

ObjectivesTo evaluate in a multicentric Italian cohort of patients with psoriatic arthritis (PsA) on secukinumab followed for 24 months: (1) the long-term effectiveness and safety of secukinumab, (2) the drug retention rate and minimal disease activity (MDA), (3) differences in the outcomes according to the biological treatment line: biologic-naïve patients (group A) versus multifailure (group B) patients.MethodsConsecutive patients with PsA receiving secukinumab were evaluated prospectively. Disease characteristics, previous/ongoing treatments, comorbidities and follow-up duration were collected. Disease activity/functional/clinimetric scores and biochemical values were recorded at baseline (T0), 6(T6), 12(T12) and 24(T24) months. Effectiveness was evaluated overtime with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug-discontinuation and MDA at T6. Infections and adverse events were recorded.Results608 patients (41.28% men; mean (SD) age 52.78 (11.33)) were enrolled; secukinumab was prescribed as first-line biological treatment in 227 (37.34%) patients, as second (or more)-line biological treatment in 381 (62.66%). Effectiveness of secukinumab was shown with an improvement in several outcomes, such as Ankylosing Spondylitis Disease Activity Score (T0=3.26 (0.88) vs T24=1.60 (0.69) ;p=0.02) and Disease Activity Index for Psoriatic Arthritis (T0=25.29 (11.14) vs T24=7.69 (4.51); p<0.01). At T24, group A showed lower Psoriasis Area Severity Index (p=0.04), erythrocyte sedimentation rate and C reactive protein (p=0.03 ;p=0.05) and joint count (p=0.03) compared with group B. At T24, MDA was achieved in 75.71% of group A and 70.37% of group B. Treatment was discontinued in 123 (20.23%) patients, mainly due to primary/secondary loss of effectiveness, and in 22 due to adverse events. Retention rate at T24 was 71% in the whole population, with some difference depending on secukinumab dosage (p=0.004) and gender (p=0.05).ConclusionsIn a real-life clinical setting, secukimumab proved safe and effective in all PsA domains, with notable drug retention rate.

scholarly journals Prospective Parallel Randomized, Double-Blind, Double-Dummy Controlled Clinical Trial Comparing Clomiphene Citrate and Metformin as the First-Line Treatment for Ovulation Induction in Nonobese Anovulatory Women with Polycystic Ovary Syndrome

2005 ◽  
Vol 90 (7) ◽  
pp. 4068-4074 ◽  
Author(s):  
Stefano Palomba ◽  
Francesco Orio ◽  
Angela Falbo ◽  
Francesco Manguso ◽  
Tiziana Russo ◽  
...  
Keyword(s):  
Polycystic Ovary ◽  
Clomiphene Citrate ◽  
Controlled Clinical Trial ◽  
Line Treatment ◽  
First Line ◽  
Ovary Syndrome ◽  
Double Blind ◽  
Group A ◽  
Group B ◽  
First Line Treatment

Abstract Context: Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients. Objective: The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS. Design: We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial. Setting: The study was conducted at the University “Magna Graecia” of Catanzaro, Catanzaro, Italy. Patients: One hundred nonobese primary infertile anovulatory women with PCOS participated. Interventions: We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each. Mean outcome measures: The main outcome measures were ovulation, pregnancy, abortion, and live-birth rates. Results: The subjects of groups A (n = 45) and B (n = 47) were studied for a total of 205 and 221 cycles, respectively. The ovulation rate was not statistically different between either treatment group (62.9 vs. 67.0%, P = 0.38), whereas the pregnancy rate was significantly higher in group A than group B (15.1 vs. 7.2%, P = 0.009). The difference found between groups A and B regarding the abortion rate was significant (9.7 vs. 37.5%, P = 0.045), whereas a positive trend was observed for the live-birth rate (83.9 vs. 56.3%, P = 0.07). The cumulative pregnancy rate was significantly higher in group A than group B (68.9 vs. 34.0%, P &lt; 0.001). Conclusions: Six-month metformin administration is significantly more effective than six-cycle CC treatment in improving fertility in anovulatory nonobese PCOS women.

scholarly journals 819 Radiomic markers associated with clinical benefit in advanced uveal melanoma patients with radiographic progression on tebentafusp

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A857-A857
Author(s):  
Volkan Beylergil ◽  
Laura Collins ◽  
Lawrence Schwartz ◽  
Thomas Eche ◽  
Binsheng Zhao ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Tumor Heterogeneity ◽  
High Probability ◽  
Radiographic Progression ◽  
Best Response ◽  
Reduction Group ◽  
Group A ◽  
Lesion Analysis ◽  
Group B ◽  
Ct And Mri

BackgroundTebentafusp, a bispecific fusion protein consisting of affinity-enhanced T cell receptor targeting a gp100 derived peptide fused to anti-CD3 effector, has shown overall survival (OS) benefit in untreated metastatic uveal melanoma (mUM). The OS benefit derives from all RECIST response categories, even progressive disease (PD). In Ph2 trial of previously treated mUM (NCT02570308), one-third (35%) of 48 evaluable patients with best response of PD had ctDNA reduction (³0.5 log reduction) and longer OS (median 16.9 months) compared to the group without ctDNA reduction (median OS 8.5 months).Methods34 of 127 mUM patients from Ph2 trial1 were selected based on best response of PD and no ctDNA reduction (Group A, n=17) or 0.5 log ctDNA reduction (Group B, n=17). One patient per group were excluded due to poor image quality or limited CT/MRI sequences. Tumor lesions were manually segmented on CT and MRI. Radiomics features were extracted at baseline and Week-8 (first assessment). The objective was to use unsupervised machine-learning to develop two signatures using 16 features to classify the two groups. The per-patient analysis signature (n=32) combined 8 volumetric features on CT-scan at baseline and change by Week-8. The per-lesion analysis signature (n=148) combined 4 features (volume and 3 radiomics features previously associated with outcome to checkpoint immunotherapy in cutaneous melanoma) at two timepoints using CT and MRI. Performance was evaluated using area under the receiver operating characteristic curve (AUC).ResultsThe median OS for Groups A and B were 8.5 and 16.9 months, respectively. In the per-patient analysis, a volumetric signature classified patients into the groups with AUC 0.71 (95%CI: 0.53–0.90) with 63% specificity and 81% sensitivity at the optimal threshold (0.57). In the per-lesion analysis, a radiomic signature reached an AUC of 0.70 (95%CI: 0.58–0.81) with 66% specificity and 74% sensitivity at the optimal threshold (0.53). Group B had lower baseline tumor lesion volume (AUC=0.65), distinct baseline tumor heterogeneity (AUC=0.66), and distinct change in tumor heterogeneity by week 8 (AUC = 0.66/0.69 on CT/MRIConclusionsA radiomic analyses of a subset of PD patients was able to predict Group B, patients with ctDNA reduction and longer OS, at a patient and lesion level. The strongest radiomic predictor by CT/MRI was decrease on treatment in tumor heterogeneity. Confirmation in a larger dataset of these signatures is needed to identify which patients may be benefiting from tebentafusp despite radiographic progression.Trial RegistrationNCT02570308Reference1. Sacco JJ, Carvajal R, Butler MO, et al. A phase (ph) II, multi-center study of the safety and efficacy of tebentafusp (tebe) (IMCgp100) in patients (pts) with metastatic uveal melanoma (mUM). Ann Oncol 2020;31:S1442–S1143.Abstract 819 Figure 1Percent change in tumor measurement from baseline at week 8 per independent review committee by Group A and BAbstract 819 Figure 2Kaplan-Meier plot comparing overall survival rates in group A and group B patientsAbstract 819 Figure 3Blue color represents a high probability of the patient being in Group A while red color indicates high probability of being in Group B

scholarly journals The Clinical Outcome in Patients with Peritoneal Metastasis

2020 ◽  
pp. 1-3
Author(s):  
Spiliotis J ◽  
◽  
Farmakis D ◽  
Raptis A ◽  
Kopanakis N ◽  
...  
Keyword(s):  
Systemic Chemotherapy ◽  
Treatment Options ◽  
Survival Rates ◽  
Peritoneal Metastases ◽  
Mortality And Morbidity ◽  
Chemotherapy Group ◽  
Significant Difference ◽  
Group A ◽  
Group B ◽  
Group D

Cytroreductive surgery (CRS) and HIPEC are controversial effective treatment options for selected patients with peritoneal metastases. We retrospectively examined 4.500 patients with peritoneal metastases from different tumors from 2005 to 2020. Patients were divided in 4 groups, surgery plus HIPEC and then systemic chemotherapy: Group A n=730, Group B n=700, R0 surgery plus systemic chemotherapy, Group C n=870, palliative surgery plus systemic chemotherapy and Group D n=2.200, palliative care and best support. The postoperative outcomes, morbidity, mortality were compared between the 4 groups. The mean survival rates Group A=24,4+10,2m, Group B= 18,4+6,3m, Group C=12,3+5,7m, Group D=5,8+2,3m (p<0.05 between Gr A vr Gr B). There was no statistically significant difference in the 30-day mortality and morbidity. In conclusion CRS + HIPEC are feasible in 16% of our patients with peritoneal metastases and are associated with pro-longed survival.

scholarly journals LETROZOLE WITH OR WITHOUT GONADOTROPIN AS A FIRST-LINE OVULATION INDUCTION IN ANOVULATORY INFERTILE WOMEN DUE TO POLYCYSTIC OVARY SYNDROME

2018 ◽  
Vol 11 (8) ◽  
pp. 129
Author(s):  
Fadia J Alizzi
Keyword(s):  
Pregnancy Rate ◽  
Ovulation Induction ◽  
Polycystic Ovary ◽  
Endometrial Thickness ◽  
Ovulation Rate ◽  
First Line ◽  
Cycle Number ◽  
Group A ◽  
Group B ◽  
Ovarian Syndrome

Objectives: The objective is to evaluate the clinical outcome of using letrozole alone or with gonadotropin as first-line ovulation induction in anovulatory infertile polycystic ovary women. Methods: A prospective single-arm study. 80 infertile polycystic ovarian syndrome (PCOS) women had been recruited between January and October 2017. Letrozole on day 2–3 of the cycle was given. The women are sorted into two groups according to the size of the dominant follicle on day 7 or 8, Group A (letrozole only group) and Group B (letrozole plus gonadotropin).Results: In our study, the overall pregnancy rate was (67.5%) and ovulation rate was 91.3%. The ovulation rate was significantly higher in Subgroup A than B (97.9% vs. 81.3%). Pregnancy rate was higher in Subgroup A (72.9% vs. 59.4%), but it was statistically not significant. The number of follicles was significantly higher in Subgroup B. Endometrial thickness, miscarriages, ovarian hyperstimulation syndrome, and multiple pregnancies were not statistically significant. Lower cycle number independently and significantly predict clinical pregnancy, while body mass index has a modest effect.Conclusions: Letrozole alone or in combination with gonadotropin as a first-line treatment in PCOS may be reasonable since this approach may improve the success rate and minimize the overall costs and risks. 

Mechanical ventricular support using pulsatile Abiomed BVS 5000 and centrifugal Biomedicus-pump in postcardiotomy shock

1994 ◽  
Vol 17 (9) ◽  
pp. 492-498 ◽  
Author(s):  
K. Minami ◽  
H. Posival ◽  
A. El-Bynayosy ◽  
M.M. Körner ◽  
H. Schrofel ◽  
...  
Keyword(s):  
Artery Bypass ◽  
Survival Rates ◽  
Valve Surgery ◽  
Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Postcardiotomy Shock ◽  
Group A ◽  
Group B ◽  
Long Term Survivors

Since we started using ventricular assist devices (VAD) in July 1987 up to August 1993, 63 of 15,650 (0.4%) patients (pts) who underwent open heart sugery were supported postoperatively by VAD at out institution. Forty-three were male and 20 female, mean age 55.5 years. In 49 pts coronary artery bypass grafting (CABG), in 8 pts valve surgery, in 3 pts combined CABG and valve surgery and in 3 pts corrective procedures for congenital heart disease were performed. Perioperative myocardial infarction was the most frequent indication (73%). In 37 of the 63 pts (58.7%) a centrifugal (Biomedicus pump (group A) was used and in 26 pts (41.3%) a pulsatile Abiomed BVS 5000 (group B). Fourteen of 37 pts (38%) in group A were weaned from the VAD and all of them were discharged. Twenty-three pts were unable to be weaned and 19 of these pts died. The remaining 4 pts were transplanted successfully and subsequently 3 died and 1 was discharged. In all, 15 pts (39%) were long-term survivors. Sixteen of 26 pts (62%) in group B were weaned from VAD and 13 (50%) of them were discharged of whom 3 died. Ten patients were unable to be weaned and 7 of these died. The remaining 3 pts were transplanted successfully. In all, 16 pts (61.5%) were long-term survivors. The shorter the interval between beginning resuscitation and application of VAD the better the outcome. Younger age, VAD installation in OR, support time between 2 and 7 days and Abiomed pump, influence the survival rate positively. Because of higher recovery and survival rates in patients assisted by Abiomed compared to the Biomedicus pump, we recommend the Abiomed pump in postcardiotomy cardiac failure.

Gallium scans in the evaluation of residual masses after chemotherapy for seminoma.

1995 ◽  
Vol 13 (11) ◽  
pp. 2784-2788 ◽  
Author(s):  
G P Warren ◽  
L H Einhorn
Keyword(s):  
False Negative ◽  
Fibrous Tissue ◽  
Salvage Chemotherapy ◽  
First Line ◽  
Chemotherapy Group ◽  
Computed Tomographic ◽  
Group A ◽  
Residual Masses ◽  
Group B

PURPOSE To assess the ability of gallium scans to determine whether residual masses consist of viable tumor or necrotic fibrous tissue after chemotherapy for seminoma. PATIENTS AND METHODS Thirty-two patients were enrolled and 27 were assessable. Patients receiving first-line or salvage chemotherapy had gallium scans performed during their first and last scheduled course of chemotherapy and results were compared with restaging computed tomographic (CT) scans and subsequent clinical outcome. RESULTS Of 27 assessable patients, 22 received first-line chemotherapy (group A) and five salvage chemotherapy (group B). Eight patients were not gallium-avid before chemotherapy despite obvious clinical and radiographic evidence of metastatic seminoma. Eighteen of 19 gallium-positive patients had a persistent mass postchemotherapy on abdominal CT. Of 16 patients in group A whose tumors were gallium-avid, all 16 had normalized gallium scans after chemotherapy. However, two of these 16 patients recurred in their original disease site. In group B, there were three patients with gallium-avid tumors and all three had normalized scans postchemotherapy. Two patients who were not gallium-avid (one each in group A and B) also developed recurrent disease. Twenty-four of 27 patients are alive with no evidence of active disease at a median follow-up time of 18 months, including 20 with more than 1 year of follow-up data. CONCLUSION Eight of 27 patients had false-negative gallium scans at the time of diagnosis. All nineteen gallium scans that were initially positive reverted to normal after chemotherapy. Two of 19 patients' follow-up gallium scans were false-negative. We therefore feel that gallium scans have minimal value in the prechemotherapy or postchemotherapy evaluation of metastatic seminoma.

scholarly journals Superior Mesenteric-Portal Vein Resection in Patients With Pancreatic Adenocarcinoma Is Safe and May Increase Survival

2017 ◽  
Vol 102 (7-8) ◽  
pp. 356-361
Author(s):  
Wei-Ding Wu ◽  
Hong-Guo Yang ◽  
Jia Wu ◽  
Kai Jiang ◽  
Kun Guo ◽  
...  
Keyword(s):  
Portal Vein ◽  
Pancreatic Adenocarcinoma ◽  
Survival Rates ◽  
Vein Wall ◽  
Venous Resection ◽  
Group A ◽  
Tumor Involvement ◽  
Artery First ◽  
Vein Resection ◽  
Group B

Extension of pancreatic adenocarcinoma into adjacent vasculature often necessitates resection of the portal vein (PV) and or superior mesenteric vein (SMV) during pancreaticoduodenectomy (PD). Our study describes the surgical technique and results of PV/SMV resection in pancreatic adenocarcinoma patients. Between January 2008 and October 2013, 252 patients underwent PD for pancreatic malignancy. A total of 42 PV/SMV resections were performed (28 men, 14 women). Patients were categorized into 2 groups according to the degree of invasion into the portal vein wall: Group A (n = 16), extended compression of the portal vein wall by the surrounding carcinoma without true invasion, and Group B (n = 26), true invasion including intramural and transmural invasion. Morbidity of the 42 patients was 35%; there was no operative mortality, and overall 1-, 3-, and 5-year survival rates were 60%, 21%, and 12%, respectively. No differences in tumor size, margin positivity, nodal positivity, or survival rates were observed between groups. Resection of the PV/SMV is safe and does not increase morbidity or mortality. Tumor involvement of the PV/SMV is not associated with histopathologic signs that are predictive of a poor prognosis. The “artery first” approach should be considered as a means to facilitate safe venous resection and reconstruction.

Phase II study of gemcitabine and oxaliplatin in patients with recurrent ovarian cancer: an Australian and New Zealand Gynaecological Oncology Group study

2007 ◽  
Vol 17 (2) ◽  
pp. 359-366 ◽  
Author(s):  
P. Harnett ◽  
M. Buck ◽  
P. Beale ◽  
A. Goldrick ◽  
S. Allan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Single Agent ◽  
Recurrent Ovarian Cancer ◽  
Ca 125 ◽  
Platinum Sensitive ◽  
Best Response ◽  
Platinum Based Chemotherapy ◽  
Group A ◽  
Intent To Treat ◽  
Group B

Gemcitabine and oxaliplatin have shown single-agent activity in relapsed ovarian cancer. This combination was used to determine response rates, time-to-event efficacy measures, and toxicity in patients with recurrent ovarian cancer. Patients with prior platinum-based chemotherapy who had measurable lesions and/or elevated CA-125 levels were identified as group A (platinum-refractory/platinum-resistant patients) and group B (platinum-sensitive patients). All patients received gemcitabine 1000 mg/m2 on days 1 and 8 and oxaliplatin 130 mg/m2 on day 8 every 21 days for up to eight cycles. Seventy-five patients (21 in group A and 54 in group B), with a median age of 58 years (range, 37–78), were enrolled. A median of six cycles (range, 1–8) was administered. By intent-to-treat analysis, 15 patients with measurable disease achieved partial response for an overall best response rate of 20.0% (9.5% in group A and 24.1% in group B). CA-125 response was observed in 48.4% patients (30.0% in group A and 57.1% in group B). Median time to progressive disease was 7.1 months (95% CI, 5.6–9.0 months) with 5.0 months in group A and 8.3 months in group B. Median overall survival was 17.8 months (95% CI, 12.9–21.3 months) with 9.2 months for group A and 20.0 months for group B. Major grade 3/4 toxicities were neutropenia (61.3%), leukopenia (24.0%), nausea (16.0%), and vomiting (22.7%). We conclude that the combination of oxaliplatin and gemcitabine is active in patients with recurrent ovarian cancer, but the regimen is unsatisfactory for further study due to modest response and relatively high toxicity.

Multicentric Real Life Evaluation of the Impact of Next-Generation Sequencing on the Clinical Management of Chronic Myeloid Malignancies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5771-5771
Author(s):  
Sophie Vantyghem ◽  
Pierre Peterlin ◽  
Sylvain Thepot ◽  
Audrey Ménard ◽  
Viviane Dubruille ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Myeloproliferative Neoplasm ◽  
Real Life ◽  
Good Prognosis ◽  
Advisory Committees ◽  
Therapeutic Decisions ◽  
Group A ◽  
Molecular Assessment ◽  
Group B ◽  
The Impact

Introduction Next generation sequencing (NGS) has allowed to improve knowledge about the genomic landscape of hematological malignancies. Somatic mutations (SM) are valuable new biomarkers but the utility of incorporating routine sequencing to guide diagnosis and therapeutic decisions remains challenging. We report here an observational multicentric study aimed at assessing the impact of SM testing by NGS in a real-life setting on the diagnosis and treatment of chronic myeloid malignancies (CMM). Patients and Method All patients who benefited from molecular assessment, between 10/2014 and 03/2019 in our University Hospital were included. All provided informed consent for data collection. All NGS requests were validated during a regional multidisciplinary concertation meeting. A custom targeted panel of 34 genes (145kbp i.e. ASXL1,BCOR, BCORL1, CBL, CSF3R, DNMT3A, ETV6, EZH2, GATA2, IDH1, IDH2, JAK2, KDM6A, KIT, KRAS, MPL, NPM1, NRAS, PIGA, PTEN, PTPN11, RAD21, RUNX1, SETBP1, SF3B1, SMC1A, SMC3, SRSF2, STAG2, TET2, TNFAIP3, TP53, U2AF1, ZRSR2) was applied on DNA extracted from peripheral blood or bone marrow samples. DNA libraries, built with the Haloplex® target enrichment protocol (Agilent Technologies, Santa Clara, CA), were paired-end sequenced (150bp reads) with a MiSeq® Instrument (Illumina, San Diego, CA). Data analysis used an in-house pipeline including three variant callings (GATK HaplotypeCaller, VarScan and SAMTools). In a first group (A), NGS indication was to search for clonal hematopoiesis (CH), defined by the presence of at least one SM, in order to confirm or rule out a diagnosis of Idiopathic Cytopenia of Undetermined Significance (ICUS), Clonal Cytopenia of Undetermined Significance (CCUS), myelodysplastic syndrome (MDS), mixed myelodysplastic/myeloproliferative neoplasm (MDS/MPN), aplastic anemia (AA)/hypoplastic myelodysplasia (hMDS) or myeloproliferative neoplasm (MPN), based on recommendations of the WHO classification. In a second group (B), the theranostic impact of SM was studied. Prognostic SMs according to Bejar (2011) were used for MDS and MDS/MPN excluding chronic myelomonocytic leukemia that were analyzed with Itzykson score (2013) and/or CPSS-Mol score (Elena 2016). Prognostic SMs according to Vannucchi (2013) were used for myelofibrosis. Results The median age of the cohort was 60 years old (range: 10-87) with a median follow up of 1.1 years from molecular assessment to last follow-up. Within group A (94 patients), the most frequent blood count anomalies were cytopenia (68%), thrombocytosis (16%), and monocytosis (13%). The karyotype was normal in 77% and failed in 5% of the cases. Non-specific abnormalities (i.e. loss of chr Y, del 20q), were found in 8% of the cases. Before molecular assessment, the diagnoses proposed were ICUS (n=37), suspicion of MDS/MPN (n=16), AA/hMDS (n=16), or MPN (n=25). CH was detected in 31 patients comforting the diagnosis of CMM for 33% of group A (8 CCUS, 3 MDS, 7 MDS/MPN, 6 medullary hypoplasia, 7 MPN) patients. Considering the patients for whom no CH was detected (n=63), the initial suspected diagnosis of CMM was ruled out in 47 patients (i.e. 50% of group A). For the 16 remaining (i.e. 17% of group A), no firm diagnosis could be retained. Within group B (95 patients), NGS identified prognosis SM in 33% of the patients, i.e. poor prognosis SM in 24, including 8/40 MDS, 10/29 MDS/MPN and 6/17 myelofibrosis and good prognosis SM(SF3B1) in 7 of them, respectively 6/40 MDS and 1/29 MDS/MPN. Prognostic SMs had a therapeutic impact in 18/95 pts (19%). Indeed 13 patients with poor prognosis SM had a therapeutic change including 12 allogeneic stem-cell transplantation and 1 hypomethylating agent. Conversely, 5 patients with a good prognosis SM or absence of poor prognosis SM had a de-escalation of treatment intensity. Conclusion The use of NGS in daily practice had a clinical impact in both diagnostic and therapeutic decisions provided that the prescription is made in a critically explored context and not as a systematic test. In this "real life" cohort, the presence or absence of SM was a useful complement for integrated diagnoses in 83% of the patients, allowing to confirm (33%), or exclude (50%) a suspected condition. Moreover, in this cohort 34% of the patients had a SM with a reported prognostic impact and the treatment was modified in 19% of the cases. Yet, it remains necessary to integrate these results with other diagnostic criteria. Disclosures Peterlin: AbbVie Inc: Consultancy; Jazz Pharma: Consultancy; Astellas: Consultancy; Daiichi-Sankyo: Consultancy. Moreau:Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Le Gouill:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Roche-Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support. Chevallier:Daiichi Sankyo: Honoraria; Incyte: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria.

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