Over-the-scope clip as first-line therapy for ulcers with high-risk bleeding stigmata is efficient compared to standard endoscopic therapy

Abstract Background and study aims Ulcers with high-risk stigmata have significant rebleeding rates despite standard endoscopic therapy. Data on over-the-scope clip (OTSC) for recurrent bleeding is promising but data on first line therapy is lacking. We report comparative outcomes of OTSC as first-line therapy versus standard endoscopic therapy in ulcers with high-risk stigmata. Patients and methods Consecutive adults who underwent endoscopic therapy for ulcers with high-risk stigmata between July 2019 to September 2020 were included. Patients were grouped into OTSC or standard therapy based on first-line therapy used on index endoscopy. Outcomes measured included: 1) intra-procedural hemostasis based on endoscopic documentation of adequate hemostasis; 2) 7-day rebleeding (> 2 g/dL drop in hemoglobin, hematochezia or hemorrhagic shock); 3) cost of endoscopic interventions; and 4) procedure duration measured as endoscope insertion to removal time. Cost of tools used during the index endoscopy was included. Results Sixty-eight patients were included, 47 were in standard therapy and 21 in the OTSC group. Hemostasis was achieved in 95.2 % in the OTSC group compared to 83.0 % in the standard therapy group (P = 0.256, number needed to treat [NNT]: 9). Procedure time was shorter in the OTSC group (23 vs. 16 minutes, P = 0.002). Cost of endoscopic interventions were comparable, P = 0.203. Early rebleeding was less often in OTSC group, two (9.5 %) compared to 10 (21.3 %) in standard therapy group, NNT 9. Conclusions Use of OTSCs as first-line treatment for ulcers bleed probably improves hemostasis and decreases early rebleeding. Use of OTSC as first-line therapy shortened procedure duration without increasing the cost of endoscopic interventions.

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Mo1310 OVER-THE-SCOPE CLIP AS FIRST-LINE THERAPY IN THE MANAGEMENT OF HIGH RISK BLEEDING PEPTIC-ULCERS: A CASE-MATCH CONTROL STUDY

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2019.03.789 ◽

2019 ◽

Vol 89 (6) ◽

pp. AB484

Author(s):

Carlos Robles-Medranda ◽

Juan M. Alcívar-Vásquez ◽

Roberto Oleas ◽

Jorge Baquerizo-Burgos ◽

Juan I. Olmos ◽

...

Keyword(s):

High Risk ◽

Peptic Ulcers ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Bleeding Peptic Ulcers ◽

Over The Scope Clip ◽

Control Study

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Over-The-Scope Clip system as a first-line therapy for high-risk bleeding peptic ulcers: a retrospective study

Surgical Endoscopy ◽

10.1007/s00464-020-07625-1 ◽

2020 ◽

Author(s):

Carlos Robles-Medranda ◽

Roberto Oleas ◽

Juan Alcívar-Vásquez ◽

Miguel Puga-Tejada ◽

Jorge Baquerizo-Burgos ◽

...

Keyword(s):

Retrospective Study ◽

High Risk ◽

Peptic Ulcers ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Bleeding Peptic Ulcers ◽

Over The Scope Clip

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Study of Pembrolizumab (MK-3475) Versus Investigator's Choice Standard Therapy for Participants With Advanced Esophageal/Esophagogastric Junction Carcinoma That Progressed After First-Line Therapy (MK-3475-181/KEYNOTE-181)-China Extension Study

Case Medical Research ◽

10.31525/ct1-nct03933449 ◽

2019 ◽

Author(s):

Keyword(s):

Standard Therapy ◽

Esophagogastric Junction ◽

Extension Study ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Esophagogastric Junction Carcinoma

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First-Line Therapy with Donor Derived HCMV-Specific T Cells Reduce Persistent HCMV Infection after Allogenic Stem Cell Transplantation

Blood ◽

10.1182/blood-2018-99-113923 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 727-727

Author(s):

Xiangyu Zhao ◽

Xuying Pei ◽

Xiaojun Huang ◽

Ying-Jun Chang ◽

Lanping Xu ◽

...

Keyword(s):

T Cells ◽

Stem Cell ◽

High Risk ◽

Hcmv Infection ◽

Antiviral Agents ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Risk Patients ◽

One Year

Abstract Background: Human cytomegalovirus (HCMV) infection, especially persistent HCMV infection, is an important cause of morbidity and mortality after allogenic stem cell transplantation (allo-SCT). Antiviral agents remain the mainstay of treatment and are recommend as the first-line therapy for HCMV. However, drugs are associated with significant toxicity, and their efficacy is limited in the absence of cell-mediated immunity. In recent years, adoptive immunotherapy with HCMV-specific T cells (CTLs) has been developed as an alternative option for HCMV, and data from previous studies have indicated that infusion of CTLs at early-stage of HCMV infection may have better benefits compared to salavage therapy. However, because CTLs remains time consuming and cost-intensive, so far there have no reports of first-line therapy with CTLs for HCMV infection, and the mechanisms driving the sustained antiviral immunity induced by adoptive T cells transfer remain undetermined. Our previous study had demonstrated that patients with acute graft-versus-host disease (aGVHD) were at high risk to develop persistent HCMV infection. Therefore, in the current study, we selected patients who developed aGVHD before HCMV reactivated and started CTLs generation in advance. This risk-stratified measure successfully selected patients who had high risk resisting to conventional anti-HCMV therapy , and spared low risk patients as well, making it feasible and financially viable to use CTLs as a first-line therapy. Aims: To provide robust support for the safety and efficacy of CTLs given as a first-line therapy for HCMV infection after allo-SCT, and gain some insight into the underlying mechanisms. Methods: Firstly, using humanized HCMV infected mice model, we explored where the adoptive transferred CTLs cells trafficked, evaluated the antiviral efficacy of CTLs and investigated the recovery of HCMV-specific immunity after T cell transfer. Secondly, we conducted a prospective clinical trial enrolled 35 allo-SCT patients who diagnosed with acute GVHD and had high risk developing persistent HCMV infection, intervened with antiviral agents combined with CTLs as first-line therapy and evaluated the long-term safety and durability of antiviral responses. As controls, we selected a cohort of 70 high-risk patients as well as another cohort of 70 low-risk patients who only received antiviral agents as first-line therapy without CTLs. We also evaluated the immune response after infusion and analyzed the association between immune recovery and HCMV clearance. Results: i) In humanized HCMV infection mice, adoptive infused CTLs had the ability to homing to organs, and effectively combated systemic HCMV infection by promoting the restoring of stem cell derived endogenous HCMV-specific immunity. ii) In clinical trial, first-line therapy with CTLs significantly reduced the rate (2.86% vs. 20.00%, P=0.018) and the cumulative incidence (HR=7.60, 95%CI=1.22-10.15, P=0.020) of persistent HCMV infection, and showed a lower one-year treatment related mortality (TRM) (HR=6.83, 95%CI=1.16-8.90, P=0.030) and a better one-year overall survival (OS) (HR=6.35, 95%CI=1.05-9.00, P=0.040) compared to high-risk control cohort. The cumulative incidence of persistent HCMV infection, one-year TRM and OS in CTL cohort were comparable to those in low-risk control cohort. Moreover, first-line therapy with CTLs promoted the quantitative and functional recovery of CTLs in patients, which was associated with HCMV clearance. Conclusion: In this study, we firstly demonstrated the safety and efficacy of CTLs administration as a first-line therapy for HCMV infection in humanized HCMV infection mice, and in a large clinical cohort study. The data provided robust support for the benefits of donor derived CTLs in treating HCMV infection as a first-line therapy, and suggested that infused CTLs might probably stimulate the recovery of donor derived HCMV-specific immunity. This trial was registered at www.clinicaltrials.gov as #NCT02985775. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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Salvage Therapies in Patients with High-Risk Relapse After Fludarabine, Cyclophosphamide, Rituximab (FCR) for Chronic Lymphocytic Leukemia: The French CLL Intergroup Experience

Blood ◽

10.1182/blood.v120.21.1796.1796 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1796-1796

Author(s):

Luc-Matthieu Fornecker ◽

Therese Aurran-Schleinitz ◽

Anne-Sophie Michallet ◽

Bruno Cazin ◽

Jehan Dupuis ◽

...

Keyword(s):

High Risk ◽

Second Line ◽

Complex Karyotype ◽

First Line ◽

Second Line Therapy ◽

High Risk Patients ◽

First Line Therapy ◽

Line Therapy ◽

Ultra High Risk ◽

Risk Patients

Abstract Abstract 1796 Introduction: FCR chemoimmunotherapy is recommended as first line therapy for fit cll patients. Since the 2007 EBMT guidelines based on the previously published trials using FCR, the definition of high risk CLL has evolved, to include biologic parameters (TP53 disruption by deletion/mutation, high b2-microglobulin level, IgVH unmutated, complex karyotype), refractoriness (progression during fluda-based regimen or within 6mo of completion), and also remission duration (high risk if PFS after FCR <24mo, ultra-high risk if TTNT <24–36mo with TP53 del/mut). However, few data are available regarding the characteristiscs, response rate and outcome of CLL patients treated in second line after FCR first line. Patients and methods: In this multicentric retrospective study, we collected data from 117 patients who relapsed after FCR first line therapy and received second-line therapy (according to NCI2008 guidelines). Results: At the time of initial FCR therapy: patients characteristics were as follows: Binet B/C 87.2%, unmutated IgVH 52.2%, del11q 25.6% (n=30/81 with FISH available), del17p 6.8% (n=8/87 with FISH available), bulk>5cm 22%, complex karyotype 21% (n=12/57 with karyotype available). FCR yielded 93% ORR, with 66% clinical CR, 27% PR, and 7% failed to respond. Median PFS and TTNT were 27mo and 32.5mo, respectively. At the time of relapse: patients characteristics were as follows: del11q 16.4% (n=19/65 with FISH available), del17p 19% (n=22/77), bulk>5cm 26%, complex karyotype 44% (n=24/54 with karyotype available). According to FCR remission duration, 11.1% of patients were considered as truly FCR-refractory, 47% had PFS<24mo, 34.2% had TTNT<24mo. TTNT<24mo after FCR was correlated to age>65y, del17p (20% vs 0%) and complex karyotype (38% vs11%), but not with gender, IgVH status, del11q, or bulk>5cm. Based on FCR-refractoriness, or TTNT<24mo and/or del17p, 53 patients were considered as ultra-high risk (45.3%). Various regimen were used for second-line treatment after FCR: R-bendamustine (n=47, 40.2%), alemtuzumab-based therapy (single agent or with chemo/dexa, n=22, 18.8%), R-CHOP (n=15, 12.8%), FCR (n=14, 12%), and other miscellaneous regimens (as follows: R-alkylator (n=6, 5.1%), R-DHAP (n=4, 3.4%), R-methylprednisolone (n=3, 2.6%), or investigational drugs (n=6, 5.1%)). Thus, 74.3% of patients received a second course including rituximab-based chemotherapy. Overall response rate was 78.4%, with 13.8% clinical CR, 64.6% PR, and 21.6% failure/stable disease. 14 pts (12%) underwent stem cell transplantations, 8 had maintenance therapy ongoing (ofatumumab, alemtuzumab, or lenalidomide). With regards to factors defining high-risk relapse, distribution of salvage therapies was as follows: As expected, a second course of FCR was seldom used in high-risk patients. Among ultra-high risk patients, 30.3% received R-benda, 11.3% Alem-based Rx, 32% R-CHOP and 18% the miscellaneous regimens described above. After second-line therapy, median PFS was 12 months, median TTNT was 14mo, and median OS was 36mo (20 deaths). On univariate analysis, complex karyotype (p=0.04) but not del17p (p=0.1), PFS<24mo (p=0.028) and TTNT<24mo (p=0.04) correlated with OS. Regarding treatment, OS was significantly improved in R-bendamustine-treated patients, as compared to alem-based or CHOP regimen (p=0.01). Most importantly, patients who received an allogeneic transplant benefited from significantly prolonged OS (at 4y, 70% vs 40%, p=0.03). Of note, only one patient treated with R-benda received allotransplant. Conclusions: This study shows that there are no consensus for second line therapy after FCR. Second line trials after FCR therapy are warranted. Definition of high-risk subsets of patients at relapse after FCR is of upmost importance in the management of CLL, to compare second-line strategies. Our data suggest that R-bendamustine is an efficient regimen even in high-risk patients (complex karyotype, PFS<24mo, TTNT<24mo). These data are important since this immunochemotherapy is now used as the backbone for combination with new compounds (ibrutinib, GS1101, GDC-199). Disclosures: Aurran-Schleinitz: Roche: Honoraria. Leblond:Roche: Advisory Board Other, Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Janssen-Cilag: Honoraria.

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Survival until First Progression and Post First Progression Survival Equally Contribute to the Overall Survival of Myeloma Patients: Differences in Patients ≤65 Years of Age Compared to Patients >65 Years

Blood ◽

10.1182/blood.v120.21.4030.4030 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4030-4030

Author(s):

Efstathios Kastritis ◽

Evangelos Terpos ◽

Maria Roussou ◽

Maria Gavriatopoulou ◽

Dimitra Gika ◽

...

Keyword(s):

High Risk ◽

Renal Impairment ◽

Initial Phase ◽

Older Patients ◽

Performance Status ◽

Age Groups ◽

First Line ◽

Younger Patients ◽

First Line Therapy ◽

Line Therapy

Abstract Abstract 4030 Age is a major prognostic factor for the outcome of patients with multiple myeloma (MM), due to more intensive treatment in younger vs. older patients, comorbidities and toxicity, resulting in early discontinuation of treatment in older patients or even differences in disease characteristics. It is believed that the longer survival of patients ≤65 years is, to a large extent, due to the receipt of more lines of therapy and thus they can have an extended survival even after relapse to first line therapy. In order to decipher these differences in the outcome of MM patients of different ages, we analyzed 438 consecutive, unselected patients who were treated in a single center (Department of Clinical Therapeutics, University of Athens School of Medicine) from April 1994 to April 2012, and compared the characteristics and outcome of patients ≤65 years (166 patients), which are usually treated with more intensive therapies (including HDT), to that of patients 66–75 years (154 patients) and >75 years of age (118 patients). Some of these patients were included in clinical trials; however, even patients who were ineligible because of poor performance status, renal impairment or comorbidities were also included, thus, being more representative of the general myeloma population. Differences in the characteristics of patients of different age groups are depicted in the table. Younger patients presented less often with ISS-3, severe anemia, renal impairment or impaired PS than older patients. However, there was no difference in the detection of high risk cytogenetics. Response was higher and deeper in younger patients. Early deaths, within 2 months from initiation of therapy, occurred more often in older patients. Median PFS was longer in younger patients. Similar proportion of patients who relapsed have received 2nd line therapy (p=0.365). Post relapse survival (PRS) was 31 months for patients ≤65 years, 20 months for patients 66–75 years and 15 months for patients >75 years (p<0.001). The difference of PRS between patients 66–75 years and patients >75 years was also significant (p=0.004). Median OS was 71 months for patients <65 years, 46 months for patients 66–75 years and 31.5 months for patients >75 years (p<0.001). Thus, it seems that the OS of patients in each age group is distributed almost equally between the initial phase of the disease and post first relapse/progression (see Table). PFS <12 months was observed in 10% of patients ≤65 years vs. 22.5% and 29% of patients 66–75 and >75 years (p=0.003). PRS for patients with a PFS<12 months was 8 months for those ≤65 years, 10 months and 6 months for patients 66–75 and >75 years. Median OS was significantly better for patients who achieved CR or VGPR (58 months) vs. patients who achieved a PR (39 months) (p<0.001). For patients <65 years who achieved a CR/VGPR median OS has not been reached (4-year OS was 79%), for patients 66–75 years was 52 months and 40 months for those >75 years (p<0.001). Among patients with a minimum follow up ≥10 years (76 patients), 5 (6.5%) remained without progression for ≥10 years (4 of them had received HDT). In order to adjust for imbalances in baseline characteristics and depth of response (CR/VGPR vs. PR), we performed a multivariate analysis in which ISS stage (p<0.001), novel agent-based first line therapy (p=0.01), CR/VGPR (p=0.005) and age ≤65 (p<0.001), but not 66–75 vs. >75 years (p=0.092) were independently associated with improved survival. In conclusion, our data indicate that the survival of MM patients is distributed almost equally between the initial phase i.e. before relapse to first line therapy, and to subsequent phases of their disease i.e. post relapse survival. This is observed across all age groups, but in patients ≤65 years the duration of first response is significantly longer, perhaps due to more intensive therapies and to less frequent early deaths. In this unselected series of patients, the 10-year free of progression rate was 6.5%. Table ≤65 years 66–75 years >75 years p-value Males 60% 43.5% 51% 0.015 ISS-1 21% 18% 9% 0.02 ISS-2 50% 46% 47% ISS-3 29% 37% 45% Hb <10 g/dl 40% 45% 53% 0.075 eGFR <60 ml/min 29% 45% 55% <0.001 Performance status ≥2 39% 55% 59% 0.001 High risk cytogenetics (n=194) 50% 48% 41% 0.5 Upfront novel agents 73.5% 63% 81% 0.023 CR 34% 27% 17% 0.005 >VGPR 56% 49% 34% 0.001 ≥PR 81% 79% 64% 0.003 Early deaths 2% 6% 12% 0.005 Median PFS (months) 34 19.5 15 0.001 Median PRS (months) 31 20 15 <0.001 Median OS (months) 71 46 31.5 <0.001 Disclosures: No relevant conflicts of interest to declare.

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Improved Outcome After Allogeneic Stem-Cell Transplantation (SCT) As Compared to Non-Allogeneic SCT Therapies in Patients with High-Risk Peripheral T-Cell Lymphomas in First Response.

Blood ◽

10.1182/blood.v120.21.3111.3111 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3111-3111

Author(s):

Margot Robles ◽

Loic Ysebaert ◽

Stephane Vigouroux ◽

Anne Huynh ◽

Marie Parrens ◽

...

Keyword(s):

Stem Cell ◽

T Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

T Cell Lymphomas ◽

Alk Positive ◽

Peripheral T Cell Lymphomas

Abstract Abstract 3111 Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of rare malignancies usually occurring in middle-aged to elderly patients (pts), with an advanced disease and unfavorable international prognostic index (IPI) scores. Excluding ALK-positive anaplastic large cell lymphomas (ALCL) and indolent mycosis fungoides, they are often characterized by a poor prognosis. There is no consensus about optimal therapy and the role of allogeneic stem-cell transplantation (allo-SCT) as first line therapy remains to be investigated. In an effort to explore this therapeutic option in younger pts, we undertook a retrospective analysis in 2 french centers. The records of all pts aged between 18 and 65 years diagnosed with PTCL in Bordeaux and Toulouse between January 2005 and April 2012 were reviewed. Cutaneous T-cell lymphomas and ALK-positive ALCL were excluded. Patients with an IPI score at diagnosis of 0/1 were excluded as well as those who never reached at least a 1st partial response according to the criteria reported by Cheson. Patients relapsing within 3 months after the 1st response and thus ineligible for allo-SCT were also excluded. The primary objective was to compare the outcome of allo-SCT (allo group) as compared to non-allogeneic SCT therapies (no-allo group) in these pts with high-risk PTCL in 1st response. Thirty-three patients were included (16 in the allo group, 17 in the no-allo group). Fifteen pts in the allo group were treated in Bordeaux where allo-SCT was always pursued during the study period in responding pts with an IPI score ≥ 2 at diagnosis. In Bordeaux, the absence of allo-SCT in 1st response was explained by the absence of a suitable donor or the refusal of the patient. The therapeutic strategy in Toulouse was different with 11 pts in the no-allo group, allowing us to undertake this retrospective comparison. In the allo group, conditioning regimes were of reduced intensity (n=12) or myeloablative (n=4). The sources of stem cells were PB (n=13), BM (n=2) or cord blood (n=1). Donors were matched related (n=7), matched unrelated (n=6), mismatched unrelated (n=2). In the whole cohort, the first chemotherapy regimes were CHOP or CHOP-like (n=31), DHAP (n=1), ICE (n=1). In the allo vs no-allo groups, the median ages at diagnosis were 54 years (20–65) vs 59 years (29–64), p = 0.5; the number of pts diagnosed before 2009 were 7 vs 9, p=0.6; the lymphoma subtypes were PTCL-NOS (4 vs 9, p=0.1), angioimmunoblastic (8 vs 6, p=0.4), others (4 vs 2, p=0.3); the IPI scores at diagnosis were 2 (5 vs 5, p=0.9), 3 (6 vs 3, p=0.2), 4/5 (5 vs 9, p=0.2); the number of pts in CR1 and PR1 were 13 vs 13, p = 0,7 and 3 vs 4, p=0.7; the number of chemotherapy lines to reach the 1st response were 1 (8 vs 15, p=0.02), 2 (4 vs 2, p=0.3) or 3 (4 vs 0, p=0.03). Five patients in the no-allo group were treated with an autologous SCT in 1st response. Three patients in the allo group were treated with autologous SCT to reach the 1st response. With a median follow-up of 34 months (8–74) after the 1st response, in the allo vs no-allo groups, the 2-year OS (figure 1) were 87% ± 8% vs 49% ± 13%, respectively (p= 0.06); the 2-year EFS (figure 2) were 81% ± 10% vs 33% ± 12%, respectively (p = 0.007). In the allo and no-allo groups, 3 and 12 pts respectively, have relapsed. In the allo and no-allo groups, 2 and 8 pts respectively, have died, all from disease progression. The modest size of our study and the potential biases inherent to such a restrospective design preclude the declaration of any firm conclusion. However, these preliminary data suggest that patients under 65 years of age with high-risk PTCL (IPI ≥2) might benefit from allo-SCT in 1st response, in comparison with non-allogeneic SCT therapies. Randomized studies are warranted to further delineate the optimal first line therapy in these patients. Our center is currently participating to such an ongoing european study comparing allo-SCT vs auto-SCT. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures: No relevant conflicts of interest to declare.

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