Julie Abraham - Academia.edu (original) (raw)

Papers by Julie Abraham

$Research paper thumbnail of A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma$

Nature Medicine

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have both demonstrated impressi... more Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have both demonstrated impressive clinical activity in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). In this study, we analyzed the outcome of 809 patients with R/R DLBCL after two or more previous lines of treatment who had a commercial chimeric antigen receptor (CAR) T cells order for axi-cel or tisa-cel and were registered in the retrospective French DESCAR-T registry study (NCT04328298). After 1:1 propensity score matching (n = 418), the best overall response rate/complete response rate (ORR/CRR) was 80%/60% versus 66%/42% for patients treated with axi-cel compared to tisa-cel, respectively (P < 0.001 for both ORR and CRR comparisons). After a median follow-up of 11.7 months, the 1-year progression-free survival was 46.6% for axi-cel and 33.2% for tisa-cel (hazard ratio (HR) = 0.61; 95% confidence interval (CI), 0.46–0.79; P = 0.0003). Overall survival (OS) was also significantly improved aft...

Revue de Médecine Interne, 2017

Introduction L’association sarcoidose et lymphome est connue avec l’apparition de lymphopathies d... more Introduction L’association sarcoidose et lymphome est connue avec l’apparition de lymphopathies dans l’evolution de sarcoidoses souvent chroniques et actives [1] . Le risque relatif de lymphome est augmente chez ces patients par rapport a la population generale avec un delai median d’apparition du lymphome de 1,5 mois apres le diagnostic de la sarcoidose [2] . Inversement, la survenue de granulomatose systemique apres la prise en charge d’une lymphopathie est de plus en plus decrite [3] . Cependant la decouverte d’une granulomatose systemique averee suite a un lymphome considere en remission peut interpeller le clinicien. Nous rapportons ici une etude retrospective descriptive de patients presentant une granulomatose systemique apres un lymphome. Patients et methodes Les patients aux antecedents de lymphome et qui ont presente par la suite une granulomatose histologiquement prouve, ont ete etudies de 2014 a 2017. Pour chaque patient nous avons releve les donnees demographiques, les ...

Blood, 2021

Introduction: We previously reported the results of the PRECIS trial with a median follow-up of 3... more Introduction: We previously reported the results of the PRECIS trial with a median follow-up of 33 months. Both whole brain radiotherapy (WBRT) and autologous stem cell transplantation (ACST) were effective according to the predetermined threshold. However, more relapses occurred in the WBRT arm. The 2-year event-free survival (EFS) from consolidation (relapse or death defined as event) were 69% (95% CI, 57% to 83%) and 87% (95% CI, 77% to 98%) after WBRT and ASCT, respectively (p = 0.03). Overall survival (OS) was similar in both arms. Cognitive impairment was observed after WBRT, whereas cognitive functions were preserved or improved after ASCT. A longer follow-up is required to better assess the impact of the treatment on relapse, survival and late complications. We report here the results of the PRECIS trial with a median follow-up of 98.3 months [min= 4,1 - max= 131.1], focusing on the per protocol population from time of consolidation. Methods: Immunocompetent patients (18 to ...

Blood, 2020

Background: AcSé Pembrolizumab is a Phase 2, open-label, single-arm, multi-cohort, multicentric s... more Background: AcSé Pembrolizumab is a Phase 2, open-label, single-arm, multi-cohort, multicentric study investigating the efficacy and safety of pembrolizumab monotherapy in patients with advanced rare cancers (NCT03012620). Here, we report the first results of Pembrolizumab in the cohort of Primary Central Nervous System Lymphoma (PCNSL). Methods: Main inclusion criteria were: relapsed or refractory PCNSL after one or several lines of treatment including high dose Methotrexate based chemotherapy, pathologically confirmed diffuse large B cell lymphoma, age>18, HIV negative, concurrent steroid medication at a dose no greater than prednisone 20 mg/day or equivalent. Patients received pembrolizumab 200 mg IV as a 30-minute infusion on Day 1 of every 21-day cycles for a maximum of 2 years. The primary endpoint was the confirmed objective response rate according to IPCG at 84 day after the start of treatment. Secondary endpoints included best response (ORR), duration of response, progre...

Blood, 2019

Introduction Prognosis of elderly patients with newly diagnosed diffuse large B cell lymphoma (DL... more Introduction Prognosis of elderly patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) remains poor as compare to young patients. Co-morbidities and physiological organ function impairment often lead to non-manageable toxicities and limit optimal chemotherapy. A decreased dose of CHOP (doxorubicin 25mg/m2 on D1, cyclophosphamide 400mg/m2 on D1, vincristine 1 mg TD on D1, and prednisone 40mg/m2 D1 to D5) chemotherapy with a conventional dose of rituximab (R-miniCHOP) displays a good compromise between efficacy and safety in this population. Lenalidomide, an oral immunomodulatory drug, in combination with RCHOP (R2-CHOP) has an acceptable toxicity and a potential higher efficacy in the non-GCB subtype, more frequent in elderly patients. The SENIOR study evaluated the tolerance and efficacy of the R2-miniCHOP regimen in comparison to the standard R-miniCHOP in patients ≥80 years with newly diagnosed DLBCL. Methods SENIOR is a multicentric, phase III, open-label, randomiz...

British Journal of Haematology, 2019

Lenalidomide maintenance therapy prolonged progression-free survival (PFS) versus placebo in elde... more Lenalidomide maintenance therapy prolonged progression-free survival (PFS) versus placebo in elderly patients with diffuse large B-cell lymphoma (DLBCL) responding to induction chemotherapy in the phase 3 REMARC study. This subpopulation analysis assessed the impact of lenalidomide maintenance and treatment-emergent adverse events (TEAEs) on healthrelated quality of life (HRQOL). Global health status (GHS), and physical functioning and fatigue subscales were evaluated in patients who completed the European Organisation for Research and Treatment of Cancer qualityof-life questionnaire-C30 v3.0. The impact of TEAEs classified post hoc as subjective (patients can feel) or observable (only measurable by physicians) on dose reductions and discontinuations was assessed. Among 457 patients (lenalidomide, n = 229; placebo, n = 228), mean (standard deviation) GHS was similar between treatment arms [68Á2 (20Á7) Versus 72Á0 (17Á8)] at randomisation and remained similar during maintenance. Patients receiving lenalidomide experienced no meaningful changes in GHS, physical functioning, or fatigue. Observable TEAEs were more common (81Á1% Versus 66Á3%) and more likely to lead to dose reductions, than subjective TEAEs in both arms. PFS was superior in the lenalidomide arm regardless of dose reduction. Lenalidomide maintenance prolonged PFS and did not negatively impact HRQOL in patients with DLBCL despite TEAEs being more common, when compared with placebo.

Blood, 2018

Introduction : High total metabolic tumor volume (TMTV) measured on 18F-FDG PET/CT before R-CHOP ... more Introduction : High total metabolic tumor volume (TMTV) measured on 18F-FDG PET/CT before R-CHOP has been shown to be significantly associated with worse progression-free survival (PFS) and overall survival (OS) in patients with diffuse large B-cell lymphoma (DLBCL; Cottereau et al. Clin Cancer Res. 2016;22:3801-9) . The REMARC study (NCT01122472) is an international, multicenter, double-blind, randomized phase III trial that assessed lenalidomide (LEN) maintenance therapy versus placebo (PBO) in 650 patients responding to R-CHOP. With a median follow-up of ~40 months, independent review demonstrated that 2 years of LEN maintenance therapy significantly improved progression-free survival (PFS); median was not reached in the LEN arm vs 58.9 months in the PBO arm (HR=0.71 [95% CI, 0.54-0.93]; p=0.0135; Thieblemont et al. J Clin Oncol. 2017;35:2473-81). Methods: For these analyses, patients enrolled in the REMARC trial who had baseline PET/CT before R-CHOP (not mandatory per study prot...

Blood, 2009

1783 Poster Board I-809 Purpose Hepatocyte Growth Factor (HGF) is a pro-angiogenic cytokine and a... more 1783 Poster Board I-809 Purpose Hepatocyte Growth Factor (HGF) is a pro-angiogenic cytokine and a mitogenic, motogenic and morphogenic factor involved in tumor growth. Previous studies have shown that HGF is secreted by plasma cells in multiple myeloma and that HGF serum levels are higher in patients with multiple myeloma and correlate with disease activity. A previous study reported that serum HGF levels were significantly higher in patients with AL amyloidosis compared to patients with multiple myeloma (Iwasaki et al. Br J Haematol. 2002;116:796-802). A preliminary study of 18 AA and AL amyloidosis patients (Shikano et al, Intern Med. 2000;39:715-9) suggested that measurement of HGF might be useful for the diagnosis of amyloidosis. To determine whether HGF may be used as a relevant diagnosis marker and prognosis factor in AL amyloidosis, we have measured HGF serum levels in patients with AL amyloidosis and patients with plasma cell dyscrasia without amyloidosis. Patients and Metho...

Blood, 2012

3632 Introduction: Although Hodgkin Lymphoma (HL) is highly curable, about 15% of patients (pts) ... more 3632 Introduction: Although Hodgkin Lymphoma (HL) is highly curable, about 15% of patients (pts) are refractory or relapsed after first line treatment. Classic prognostic scores (e.g. IPS) are useful for identifying high risk pts, who need intensive treatment, and low risk pts, who beneficiate de-escalation to minimize side effects. However, they are not enough suitable to predict outcomes. Consequently, finding new complementary tools for detecting refractory or relapsing pts, remains a challenge. Fluorodeoxyglucose (FDG)-PET/CT involvement in initial staging has been widely studied. Although clinical or CT tumor volume is an important prognostic factor, metabolic tumor volume (MTV) is not enough explored. We performed a study to 1) determine whether MTV and maximum standardized uptake value (SUV) max could be new prognostic markers and 2) compare metabolic tissue heterogeneity with CD68 expression, a promising new prognostic factor linked with inflammatory microenvironment. Patien...

Hematological Oncology, 2019

(47%) were positive for cHL and all underwent salvage chemotherapy followed by autologous stem ce... more (47%) were positive for cHL and all underwent salvage chemotherapy followed by autologous stem cell transplant (CT+ASCT) (group 1a). Among biopsy-negative cases (group 1b), 4/10 were observed and 6/10 received radiotherapy (RT) consolidation. Among the nonbiopsied cases (group 2), 10/18 were observed (group 2a), 7/18 received RT (group 2b), and 1/18 underwent CT+ASCT (group 2c). Patients of group 2a had a repeat PET scan after a median time of 13 weeks (range 4-35) and then only 7/10 showed persistent FDG uptake or progression disease. 6/6 biopsies performed at this time were positive and all cases received CT+ASCT. No biopsy was done in 1/7 case considered to be thymic rebound. Among patients of group 1a, 2a and 2c receiving CT-ASCT, complete remission (CR) was obtained in 11/16 (69%); 8/13 (61%) patients from group 1b or 2b receiving consolidative RT remained in CR; 2/4 cases observed after a negative biopsy subsequently progressed; 3/10 cases of group 2a converted to PET negativity and remained in CR. (Fig 1) With a median follow up of 38.4 months, no survival difference between groups 1 and 2 was observed. On radiological review of 34/37 patients at the end of therapy, Deauville scores (DS) of the PET images were as follows: 3 cases DS2, 4 DS3, 12 DS4, 12 DS5, 3 thymic rebound (DSX). The rate of relapse was 1/3 (33%) for DS2, 1/4 (25%) for DS3, 4/12 (33%) for DS4, 10/12 (83%) for DS5 and 1/3 (33%) for DSX. Conclusions: Within the limitations of this small retrospective cohort, biopsy of post-treatment persistent mediastinal PET-positivity in cHL patients is positive in less than half the cases and DS was relatively unhelpful in selecting patients with potentially refractory disease. We conclude that adopting a "wait-and-see" strategy with a repeat PET scan reassessment 8-12 weeks later increases the likelihood that the subsequent biopsy will be positive without compromising the outcome and may be the preferred approach.

$Research paper thumbnail of Efficacy of chemotherapy or chemo-anti-PD-1 combination after failed anti-PD-1 therapy for relapsed and refractory Hodgkin lymphoma: A series from Lysa centers$

American journal of hematology, Jan 8, 2018

Anti-PD-1 therapy provides high response rates in Hodgkin lymphoma (HL) patients who have relapse... more Anti-PD-1 therapy provides high response rates in Hodgkin lymphoma (HL) patients who have relapsed or are refractory (R/R) to autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV), but median progression free survival (PFS) is only one year. The efficacy of treatment following anti-PD-1 is not well known. We retrospectively investigated the efficacy of salvage therapies for unsatisfactory response to anti-PD-1 therapy, assessed by PET-CT according to the Lugano criteria, in 30 R/R HL patients. Patients were highly pre-treated before anti-PD-1 (70% received ASCT and 93% BV). Unsatisfactory responses to anti-PD1 therapy were progressive disease (PD) (n=24) and partial response (PR) (n=6). For the 24 PD patients, median anti-PD-1 related PFS was 7.5 months (95%CI, 5.7-11.6); 17 received subsequent CT alone (Group 1) and 7 received CT in addition to anti-PD-1 (Group 2). 16/24 patients (67%) obtained an objective response. In the 15 patients treated with the same CT, t...

Nutrition, 2017

To the best of our knowledge, few studies have evaluated the nutritional status in patients with ... more To the best of our knowledge, few studies have evaluated the nutritional status in patients with acute myeloid leukemia (AML) during induction treatment. The aim of this retrospective study was to describe nutritional status of newly diagnosed adult patients with AML at admission and during induction chemotherapy. We included consecutive newly diagnosed adult patients with AML who were admitted to the Department of Hematology (Limoges University Hospital) from April 2010 to January 2014. Nutritional assessment included body mass index (BMI) and weight loss to diagnose undernutrition. Weekly laboratory tests were collected and total energy expenditure was calculated to adapt food intake. Of 95 patients, 14 (15%) presented with undernutrition at admission: low BMI values (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and weight loss &amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;5% for 9.5% patients. After chemotherapy induction, 17 patients (18%) were undernutrition (P = 0.05). Patients without undernutrition had a significantly lower median weight, BMI, and serum albumin level at discharge compared with their admission values (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05); whereas their serum transthyretin levels were higher (P = 0.03). They also had shorter hospital stays than patients with undernutrition (31 versus 39 d; P = 0.03) and longer survival at 12 mo (89.9 versus 58.3%; P = 0.002). Patients with AML with good nutritional status undergoing induction chemotherapy have shorter hospital stays and longer survival.

Therapeutic drug monitoring, Apr 11, 2017

MRP2/ABCC2, an efflux transporter expressed at the proximal renal tubule, is rate limiting for ur... more MRP2/ABCC2, an efflux transporter expressed at the proximal renal tubule, is rate limiting for urine excretion of coproporphyrin (UCP) isomers I and III, translating in high UCP (I/(I+III)) ratio in MRP2-deficient patients presenting with the Dubin-Johnson Syndrome. MRP2 is also a major contributor to methotrexate (MTX) clearance. As MTX is both a substrate and an inhibitor of MRP2, time course of the concentrations of MTX in blood could induce functional modification of MRP2 over time, which in turn can modify its own elimination rate. A three-parameter time-dependent MTX population pharmacokinetic model based on a power function accounting for non-linearity in its clearance was developed using Pmetrics® in a first cohort of 41 patients (76 pharmacokinetic profiles) and compared to a previously published two-compartment model developed with NONMEM® and a three-compartment model developed with ITSIM®. In a second cohort (62 patients and 62 pharmacokinetic profiles), the association ...

Pharmacogenomics, 2016

Aim: To investigate the potential influence of variants in genes involved in the calcineurin path... more Aim: To investigate the potential influence of variants in genes involved in the calcineurin pathway on the efficacy and toxicity of calcineurin inhibitors in renal transplantation. Materials & methods: Twenty-three polymorphisms in thirteen genes were tested in 381 renal transplant recipients receiving ciclosporin (n = 221) or tacrolimus (n = 160) and mycophenolate mofetil. Data were collected prospectively over the first year post-transplantation. Results: Multivariate survival analyses revealed no genetic associations with biopsy proven acute graft rejection and serious infections. Donor–recipient Cytomegalovirus mismatch was the only variable associated with serious infection. Conclusion: This large exploratory study casts doubts on the potential interest of genetic biomarkers related to CNI pharmacodynamics but associations with other phenotypes in transplantation deserve further studies.

Liver International, 2015

Hepatitis C virus-related B-cell proliferation is a model of virus-driven autoimmune/neoplastic d... more Hepatitis C virus-related B-cell proliferation is a model of virus-driven autoimmune/neoplastic disorder leading to mixed cryoglobulinemia and/or B-cell non Hodgkin lymphoma. These lymphomas are often marginal zone lymphomas or diffuse large B-cell lymphomas. Peginterferon/Ribavirin therapy has proved its crucial role in the cure of these non-Hodgkin lymphomas, but data are lacking concerning new direct anti-viral agents. We report five cases of Hepatitis C virus-associated B-cell non Hodgkin lymphoma treated with direct anti-viral agents: two marginal zone lymphomas received direct anti-viral agents alone (one with a leukemic phase only, one with splenic and deep lymph nodes localizations); one renal marginal zone lymphoma with renal insufficiency received direct anti-viral agents and 4 rituximab infusions simultaneously; two diffuse large B-cell lymphomas were treated with direct ant-viral agents following chemotherapy. Sustained virological response was obtained in all patients, and complete remission of NHL was noted six months after cessation of any treatment except for one patient with a persistent small leukemic phase. Direct anti-viral agents might be proposed as a first-line treatment in marginal zone lymphomas in the case of no life-threatening complications with the precaution of a long-term follow-up. In the setting of diffuse large B-cell lymphomas, well-tolerated direct anti-viral agents could potentially be introduced very early not only to prevent relapse of these lymphomas but also to limit the liver toxicity of chemotherapy and rituximab by preventing outbreaks of viral load. New observations and trials should support these assumptions. This article is protected by copyright. All rights reserved.

Néphrologie & Thérapeutique, 2011

Leukemia & Lymphoma, 2014

Abstract Finding new prognostic factors to identify patients with Hodgkin lymphoma (HL) at risk o... more Abstract Finding new prognostic factors to identify patients with Hodgkin lymphoma (HL) at risk of treatment resistance or relapse remains challenging in daily practice. We evaluated the relationship between CD68 expression, interim positron emission tomography (iPET) results and outcome in 158 patients with HL diagnosed from February 1995 to July 2011. Immunohistochemistry (anti-CD68) gave two groups: low with ≤ 25% positive cells (121 patients) and high with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 25% (37 patients). Five-year overall survival was higher in the low group (88.4% vs. 63.2%, p = 0.0151), as was progression-free survival (74.5% vs. 40.7%, p = 0.0003). In 68 patients evaluable, iPET correlated with CD68: 13/52 patients (25%) in the low group had positive iPET as compared to 11/16 patients (68%) in the high group (p = 0.0016). This study confirms the prognostic value of CD68 in HL. We found a correlation between CD68 and iPET suggesting potential for a better stratification.

Intensive Care Medicine, 2007

Objective: We sought to evaluate the efficacy of a limited training dedicated to residents withou... more Objective: We sought to evaluate the efficacy of a limited training dedicated to residents without knowledge in ultrasound for performing goal-oriented echocardiography in ICU patients. Design: Prospective pilot observational study. Setting: Medical-surgical ICU of a teaching hospital. Patients: 61 consecutive adult ICU patients (SAPS II score: 38 ± 17; 46 ventilated patients) requiring a transthoracic echocardiography were studied. Interventions: After a curriculum including a 3-h training course and 5 h of hands-on training, one of four noncardiologist residents and an intensivist experienced in ultrasound subsequently performed hand-held echocardiography (HHE), independently and in random order. Assessable "rule in, rule out" clinical questions were purposely limited to easily identifiable conditions by the sole use of two-dimensional imaging. Measurements and results: When compared with residents, the experienced intensivist performed shorter examinations (4 ± 1 vs. 11 ± 4 min: p < 0.0001) and had significantly less unsolved clinical questions [3 (0.8%) vs.

American Journal of Hematology, 2013

POEMS syndrome is a rare disorder characterized by polyneuropathy, monoclonal gammopathy, multior... more POEMS syndrome is a rare disorder characterized by polyneuropathy, monoclonal gammopathy, multiorgan involvement, and elevated vascular endothelial growth factor levels. Localized bone lesions require irradiation, whereas young patients with disseminated disease receive intensive treatment with stem cell support. Treatment of older and non responding patients is not yet standardized. We report the use of a combination of lenalidomide and dexamethasone in 20 patients with POEMS syndrome. Four patients were newly diagnosed, and 16 had relapsed or progressed after treatment. All but one of the patients responded: clinical improvements were noted in neuropathies (16/20) organomegaly (13/13), peripheral edema (14/15), and pulmonary hypertension (5/5). At least a very good partial response was noted in 68% of patients, with partial responses in 26%. Serum VEGF levels fell markedly in all 17 patients with available values. Twelve patients had 18-FDG-PET/CT at diagnosis (11 with positive findings), and nine patients during follow-up. The number of lesions fell markedly in five cases and remained stable in two cases, while two patients became negative. During a median follow-up of 22 months, four patients relapsed. Toxicity, predominantly hematological, was mild and manageable. Lenalidomide thus appears to be effective in POEMS syndrome, inducing high rate of clinical and biological responses. Am.