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Context Some women living with type 1 diabetes complain of changes in glucose values according to the different phases of menstruation. Objective To evaluate this variability through continuous glucose monitoring (CGM) data in type 1 diabetes patients. Design Observational study. Setting Ambulatory data, recruitment in 2 centers in the Paris region. Patients Twenty-four women with type 1 diabetes having spontaneous menstrual cycles. Intervention Collection of CGM data for 62 spontaneous menstrual cycles, with evaluation of five 3-day phases during each cycle: (1) early follicular (menstruations), (2) mid-follicular, (3) peri-ovulatory, (4) mid-luteal, and (5) late luteal. Main outcome measure Time in range (TIR, prespecified). Results TIR decreased for each consecutive phase (61 ± 18%; 59 ± 18%; 59 ± 20%; 57 ± 18%; and 55 ± 20%, P = 0.02). The linear mixed model highlighted a decrease in TIR in the mid-luteal (P = 0.03) and late luteal (P Conclusion In most of the study population, glucose levels rose linearly throughout the menstrual cycle, reaching a maximum in the late luteal phase. A sharp decrease was seen for most participants at the beginning of menstrual bleeding. This should be taken into consideration in daily care of type 1 diabetes patients to avoid hypoglycemia.

We report a randomized prospective phase 3 study (CLL7), designed to evaluate the efficacy of fludarabine, cyclophosphamide, and rituximab (FCR) in patients with an early-stage high-risk chronic lymphocytic leukemia (CLL). Eight hundred patients with untreated-stage Binet A disease were enrolled as intent-to-treat population and assessed for four prognostic markers: lymphocyte doubling time 10 U/L, unmutated IGHV genes, and unfavorable cytogenetics (del(11q)/del(17p)/trisomy 12). Two hundred and one patients with ≥2 risk features were classified as high-risk CLL and 1:1 randomized to receive either immediate therapy with 6xFCR (Hi-FCR, 100 patients), or to be observed according to standard of care (Hi-W&W, 101 patients). The overall response rate after early FCR was 92.7%. Common adverse events were hematological toxicities and infections (61.0%/41.5% of patients, respectively). After median observation time of 55.6 (0–99.2) months, event-free survival was significantly prolonged in Hi-FCR compared with Hi-W&W patients (median not reached vs. 18.5 months, p p = 0.864). In conclusion, although FCR is efficient to induce remissions in the Binet A high-risk CLL, our data do not provide evidence that alters the current standard of care “watch and wait” for these patients.

Immunocompromised individuals such as patients with chronic lymphocytic leukemia (CLL) are at risk of impaired immune responses to vaccination. The objective of our study was to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific antibody responses in patients with CLL after the first, second, and third doses of the BNT162b2 or mRNA-1273 vaccines and after a single dose for patients with confirmed previous COVID-19. In all, 530 patients were included in the study. Patients received 2 doses at a 4-week interval and a third dose if they were seronegative after the second dose. Response rate was 27% after dose 1 and 52% after dose 2. Post-dose 2 treatment-naïve patients had the highest response rate (72%) followed by patients previously treated by chemoimmunotherapy (60%). Among patients receiving therapy, those receiving Bruton tyrosine kinase inhibitor alone (22%) or in combination with anti-CD20 monoclonal antibodies or venetoclax (0%) had the poorer response rate whereas patients who received venetoclax monotherapy achieved a significantly higher response rate (52%). A multivariable analysis identified age older than 65 years, ongoing CLL treatment, and gamma globulin ≤6 g/L as independent predictors of the absence of seroconversion. Post-dose 2 seronegative patients had a global response rate of 35% after dose 3. This study provides an argument for the use of a third dose and for prophylactic SARS-CoV-2 neutralizing monoclonal antibodies.

To investigate which cytokines, chemokines and growth factors are involved in the immunopathogenesis of idiopathic uveitis, and whether cytokine profiles are associated with. Serum and aqueous humor (AH) samples of 75 patients with idiopathic uveitis were analyzed by multiplex immunoassay. Infectious controls consisted of 16 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. Noninfectious controls consisted of 7 patients with Behçet disease related uveitis and 15 patients with sarcoidosis related uveitis. The control group consisted of AH and serum samples from 47 noninflammatory control patients with age-related cataract. In each sample, 27 immune mediators ± IL-21 and IL-23 were measured. In idiopathic uveitis, 13 of the 29 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-12, G-CSF, GM-CSF, MCP-1, IP-10, TNF-α and VEGF, were significantly elevated in the aqueous humor when compared to all controls. Moreover, IL-17, IP-10, and IL-21, were significantly elevated in the serum when compared to all controls. We clustered 4 subgroups of idiopathic uveitis using a statistical analysis of hierarchical unsupervised classification, characterized by the order of magnitude of concentrations of intraocular cytokines. The pathogenesis of idiopathic uveitis is characterized by the presence of predominantly proinflammatory cytokines and chemokines and vascular endothelial growth factor with high expression levels as compared to other causes of uveitis. There are indications for obvious Th-1/ IL21-Th17 pathways but also IL9-Th9 and increased IFN-γ-inducing cytokine (IL12) and IFN-γ-inducible CXC chemokine (IP-10). The combined data suggest that immune mediator expression is different among idiopathic uveitis. This study suggests various clusters among the idiopathic uveitis group rather than one specific uveitis entity.

Background Reduced mortality at 28 days in patients treated with corticosteroids was demonstrated, but this result was not confirmed by certain large epidemiological studies. Our aim was to determine whether corticosteroids improve the outcomes of our patients hospitalized with COVID-19 pneumonia. Methods Our retrospective, single centre cohort study included consecutive patients hospitalized for moderate to severe COVID-19 pneumonia between March 15 and April 15 2020. An early short course of corticosteroids was given during the second phase of the study. The primary composite endpoint was the need for mechanical ventilation or mortality within 28 days of admission. A multivariate logistic regression model was used to estimate the propensity score, i.e. the probability of each patient receiving corticosteroid therapy based on the initial variables. Results About 120 consecutive patients were included, 39 in the “corticosteroids group”, 81 in the “no corticosteroids group”; their mean ages (±SD) were 66.4 ± 14.1 and 66.1 ± 15.2 years, respectively. Mechanical ventilation-free survival at 28 days was higher in the “corticosteroids group” than in the “no corticosteroids group” (71% and 29% of cases, respectively, p

Despite appealing characteristics for the clinical trials setting, Bayesian inference methods remain scarcely used, especially in randomized controlled clinical trials (RCT). This is particularly true when dealing with a survival endpoint, likely due to the additional complexities to model specifications. We propose to use Bayesian inference to estimate the treatment effect in this setting, using a proportional hazards (PH) model for right-censored data. Implementation of such an estimation process is illustrated on two working examples from cancer RCTs, the ALLOZITHRO and the CLL7-SA trials, both originally analyzed using a frequentist approach. In these two different settings, we show that Bayesian sequential analyses can provide early insight on treatment effect in RCTs. Relying on posterior distributions and predictive posterior probabilities, we find that Bayesian sequential analyses of the ALLOZITHRO trial, which was terminated early due to an unanticipated deleterious effect of the intervention on survival, allow quantifying early that the treatment effect was opposite to what was expected. Then, incorporating historical data in the sequential analyses of the CLL7-SA trial would have allowed the treatment effect to be closer to the protocol hypothesis. These post-hoc results give grounds to advocate for a wider use of Bayesian approaches in RCTs, including those with right-censored endpoints, as informative decision tools.

Background:. The efficacy of high flow nasal canula oxygen therapy (HFNO) to prevent invasive mechanical ventilation (IMV) is not well established in severe coronavirus disease 2019 (COVID-19). The aim of this study was to compare the risk of intubation between two strategies of oxygenation (conventional oxygenation and HFNO) in critically ill COVID 19 patientsMethods: This was a multicenter retrospective case series witch took place in two intensive care units (ICU) of tertiary hospitals in the Paris region from March 11, to May 3, 2020. We enrolled consecutive patients hospitalized for COVID-19 and acute respiratory failure (ARF) who did not receive IMV at ICU admission. The primary outcome was the rate of IMV after ICU admission. Secondary outcomes were death at day 28 and day 60, length of ICU stay, ventilator-free days and number of patients with ventilator-free days >14 days. Data from the HFNO group were compared with those from the standard oxygen therapy (SOT) group.ResultsAmong 138 patients who met the inclusion criteria, 62 (45%) were treated with SOT alone, and 76 (55%) with HFNO. In HFNO group, 39/76 (51%) patients were intubated and 46/62 (74%) in SOT group. After using a standard logistic regression on the original sample, HFNO was associated with significantly lower rate IMV (OR [IC-95%] 0.37 [0.18 – 0.76] p = 0.007). After propensity score application, HFNO was still associated with a lower rate of intubation (OR [IC-95%] 0.31 [0.14-0.66] p = 0.002). Length of ICU stay and mortality at day 28 and day 60 did not significantly differ between HFNO and SOT groups after propensity score application. In a univariate analysis, ventilator-free days at days 28 was higher in HNFO group (21 days vs 10 days, p=0.005). The number of patients with ventilator free-days >14 days was higher in HFNO group after propensity score application (66% vs 39%; OR 3.91[1.91-7.99], p=0.0002).ConclusionsHigh flow nasal canula oxygen for ARF due to COVID-19 reduces the need for intubation.

International audience; No abstract available

Ischemic microangiopathy was clearly identified in sickle cell disease (SCD) using fluorescein angiography. A prospective observational clinical study was conducted to assess the foveal avascular zone (FAZ) area and explore perifoveal microvasculature changes in the superficial (SCP) and deep (DCP) capillary plexus using optical coherence tomography angiography (OCTA) and compare two genotypes—HbS/HbS (HbSS) and HbS/HbC (HbSC)-to control. All consecutive patients with electrophoretic confirmation of SCD were included. Swept-source OCTA scans (Triton Plus, Topcon, Tokyo, Japan) with a 3 × 3-mm scanning area and ultra-wide field (UWF) retinography (California, Optos, Fife, Scotland) were recorded for all patients. For OCTA analysis, preset parameters were used to segment the SCP and DCP. The FAZ area was manually assessed. The number of vascular branching points was automatically assessed based on the vascular skeletonization using ImageJ software. Eyes were staged based on Goldberg’s classification of SCD retinopathy (SCDR) using UWF imaging. Forty-six eyes of 24 patients were included in the HbSS (n = 27) and HbSC (n = 19) groups and 16 eyes of 8 unaffected patients in a control group. In the DCP, the FAZ was significantly larger in the HbSC (p = 0.0001) and HbSS (p = 0.0004) groups compared to controls. The FAZ area in the SCP, CRT and number of superficial vascular branching points did not significantly differ between both genotypes. There were less branching points in the HbSC (p = 0.034) and HbSS (p = 0.0014) groups than in controls. The Goldberg stage was significantly higher in the HbSC group than in the HbSS group (2.21 vs. 1.22, p = 0.0062). OCTA provides useful information on macular microvasculature and structural alterations associated with SCDR. Ischemic abnormalities are more predominant in the DCP in case of SCDR and no difference was found between genotypes of patients visually asymptomatic.

In total, 279 patients with hairy-cell leukemia (HCL) were analyzed, with a median follow-up of 10 years. Data were collected up to June 2018. We analyzed responses to treatment, relapses, survival, and the occurrence of second malignancies during follow-up. The median age was 59 years. In total, 208 patients (75%) were treated with purine analogs (PNAs), either cladribine (159) or pentosatin (49), as the first-line therapy. After a median follow-up of 127 months, the median overall survival was 27 years, and the median relapse-free survival (RFS) was 11 years. The cumulative 10-year relapse incidence was 39%. In patients receiving second-line therapy, the median RFS was 7 years. For the second-line therapy, using the same or another PNA was equivalent. We identified 68 second malignancies in 59 patients: 49 solid cancers and 19 hematological malignancies. The 10-year cumulative incidences of cancers, solid tumors, and hematological malignancies were 15%, 11%, and 5.0%, respectively, and the standardized incidence ratios were 2.22, 1.81, and 6.67, respectively. In multivariate analysis, PNA was not a risk factor for second malignancies. HCL patients have a good long-term prognosis. PNAs are the first-line treatment. HCL patients require long-term follow-up because of their relatively increased risk of second malignancies.

Background Lung recruitment at birth has been advocated as an effective method of improving the respiratory transition at birth. Sustained inflations (SI) and dynamic positive end-expiratory pressure (PEEP) were assessed in clinical and animal studies to define the optimal level. Our working hypothesis was that very low gestational age infants (VLGAI) Methods Between 2014 and 2016, 91 and 72 inborn VLGAI, requiring a respiratory support beyond a continuous positive airway pressure (CPAP) = 5 cmH2O, were enrolled before and after introducing these manoeuvers based on progressive increase in SI up to 15 s, with simultaneous gradual increase in PEEP up to 15 cmH2O, according to the cardiorespiratory response. Retrospective comparisons of the incidence of mechanical ventilation (MV) Results Among extremely low gestational age infants (ELGAI) Conclusions In our setting, combining two individualized lung recruitment maneuvers at birth was feasible and may be beneficial on short-term and before discharge pulmonary outcomes. A randomized controlled trial is needed to confirm these results.

The purpose of this study was to quantify retinal capillary density and foveal avascular zone (FAZ) area in healthy subjects according to their ethnicity, using optical coherence tomography angiography (OCTA). In this cross-sectional study, all eyes underwent swept-source OCTA (Triton, Topcon, Tokyo, Japan). Macular OCTA scans (3 × 3 mm) were obtained in healthy white Caucasian and black African subjects. The FAZ area and capillary density in both the superficial (SCP) and deep capillary plexuses (DCP) were automatically measured using a custom-made software combining vessel binarization and skeletonization. Twelve eyes of 12 healthy Caucasians and 15 eyes of 15 healthy black Africans were included in the analysis. The mean FAZ area was significantly smaller, and the overall vessel density (VD) was higher in the SCP and DCP of Caucasians compared to black Africans. The mean FAZ area was 0.26 ± 0.008 mm2 in the SCP and 0.25 ± 0.05 mm2 in the DCP in Caucasians versus 0.33 ± 0.08 mm2 in the SCP (p = 0.01) and 0.37 ± 0.1 mm2 in the DCP (p = 0.03) in Africans. In the SCP and DCP, the mean VD was, respectively, 40.5 ± 0.8% and 47.1 ± 0.5% in Caucasians versus 34.3 ± 1% (p = 0.008) and 40.6 ± 0.9% in Africans (p

Fertility preservation embraces different techniques developed to improve young women chances of becoming mothers after healing. Among them, in vitro maturation (IVM) procedure is based on oocyte retrieval without any gonadotropin treatment, feasible under locoregional or local anesthesia, with very low operative complications. The present retrospective analysis of a preliminary case series of 25 women diagnosed with Hodgkin or non-Hodgkin lymphoma aims to evaluate the feasibility of IVM for urgent fertility preservation purposes in hematological context. A median of five mature oocytes was cryopreserved after one cycle of IVM, performed without delaying the start of the chemotherapy (median delay from histological diagnosis to start of the chemotherapy 17.5 days). No association was found between lymphomas' characteristics and the number of recovered or frozen oocytes. Although experimental, this technique could be relevant when fertility preservation has to be performed within a short time frame and without additional surgery nor any risk of malignant cells reintroduction.

International audience; Coherent light scattered by tissues brings structural and dynamic information, at depth, that standard imaging techniques cannot reach. Dynamics of cells or sub-cellular elements can be measured thanks to dynamic light scattering in thin samples (single scattering regime) or thanks to diffusive wave spectroscopy in thick samples (diffusion regime). Here, we address the intermediate regime and provide an analytical relationship between scattered light fluctuations and the distribution of cell displacements as a function of time. We illustrate our method by characterizing cell motility inside half millimeter thick multicellular aggregates.

PURPOSE To evaluate first-line pembrolizumab monotherapy efficacy and safety in patients with unresectable cutaneous squamous cell carcinomas (CSCCs). PATIENTS AND METHODS Patients, predominantly men, with their CSSCs’ immunohistochemically determined programmed cell death-ligand 1 (PD-L1) status determined (tumor proportion score threshold, 1%), received pembrolizumab (200 mg every 3 weeks). The primary endpoint was the 39-patient primary cohort’s objective response rate at week 15 (ORRW15). Secondary objectives were best ORR, overall survival (OS), progression-free survival (PFS), duration of response (DOR), safety, ORR according to PD-L1 status and health-related quality of life using Functional Assessment of Cancer Therapy–General (FACT-G) score. An 18-patient expansion cohort, recruited to power the study to evaluate the ORRW15 difference between PD-L1+ and PD-L1– patients, was assessed for ORR, disease control rate, and safety, but not survival. RESULTS Median age of all patients was 79 years. The primary cohort’s ORRW15 was 41% (95% CI, 26% to 58%), including 13 partial and 3 complete responses. Best responses were 8 partial and 8 complete responses. At a median follow-up of 22.4 months, respective median PFS, DOR, and OS were 6.7 months, not reached, and 25.3 months, respectively. Pembrolizumab-related adverse events affected 71% of the patients, and 4 (7%) were grade ≥ 3. One death was related to rapid CSCC progression; another resulted from a fatal second aggressive head and neck squamous cell carcinoma diagnosed 15 weeks postinclusion. ORRW15 for the entire population was 42%; it was significantly higher for PD-L1+ patients (55%) versus PD-L1– patients (17%; P = .02). Responders’ W15 total FACT-G score had improved ( P = .025) compared with nonresponders. CONCLUSION First-line pembrolizumab monotherapy exhibited promising anti-CSCC activity, with durable responses and manageable safety. PD-L1 positivity appears to be predictive of pembrolizumab efficacy.

As a result of significant recent developments, the management of patients with chronic lymphocytic leukemia (CLL) is changing, and new therapeutic options will continue to emerge in the near future. The recommendations of the French Innovative Leukemia Organization (FILO-CLL) group presented here are intended to provide practical recommendations for physicians taking care of CLL patients, taking into account the availability of both biological tests and therapies in daily practice in France at the time of publication. This text details the documented information and guidelines on diagnosis, indications for treatment, infectious complications and therapeutic strategies in frontline and relapsed CLL as well as in particular conditions such as autoimmune cytopenia or Richter syndrome.

Introduction In previously untreated, medically fit patients with chronic lymphocytic leukaemia (CLL) and no 17p deletion, there is current research interest in improving survival outcomes and potentially sparing some patients from the standard 6 cycles of fludarabine, cyclophosphamide and rituximab (FCR). The phase II ICLL-07 (NCT02666898) trial, conducted by the French Innovative Leukemia Organization (FILO), aimed to explore the efficacy of obinutuzumab and ibrutinib treatment induction for 9 months, followed by a minimal residual disease (MRD)-driven strategy. Methods Following assessment at Month 9, patients in complete response (CR) with bone marrow (BM) MRD ResultsBetween 10/2015 and 05/2017, 135 patients were enrolled. At Month 9, only 8% of patients reached CR with BM MRD Conclusion These findings from the ICLL-07 trial demonstrated that, in previously untreated, medically fit patients with CLL and no 17p deletion, treatment induction with obinutuzumab and ibrutinib followed by an MRD-driven strategy yielded a high rate of CR with BM and PB MRD Disclosures Salles: Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Amgen: Honoraria, Other: Educational events. Leblond:Gilead: Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cartron:Roche, Celgene: Consultancy; Sanofi, Gilead, Janssen, Roche, Celgene: Honoraria. Cymbalista:Sunesis: Research Funding; Roche: Research Funding; Janssen: Honoraria; Abbvie: Honoraria; AstraZeneca: Honoraria; Gilead: Honoraria. Le Garff-Tavernier:Alexion: Consultancy, Honoraria. Letestu:Alexion: Membership on an entity's Board of Directors or advisory committees, Other: speaker fee, expert contracts; Roche: Membership on an entity's Board of Directors or advisory committees, Other: speaker fee, expert contracts; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: speaker fee, expert contracts; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: speaker fee, expert contracts. Feugier:janssen: Honoraria, Research Funding, Speakers Bureau; gilead: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau.

International audience; Background & aims: the obesity survival paradox is an emergent issue in oncology, but its existence remains unclear particularly in older cancer patients. We aimed to assess the obesity survival paradox in older cancer patients.Methods: all consecutive cancer outpatients 65 years and older referred for geriatric assessment (GA) before a decision on cancer treatment between November 2013 and September 2016 were enrolled in the PF-EC cohort study. The main outcome was 6-month mortality. A Cox univariate and multivariate proportional hazard regression models were performed with baseline GA, oncological variables (cancer site, extension and treatment modalities) and C-reactive protein (CRP). We assessed the prognostic value of body mass index categories (i.e. malnutrition = 30 kg/m(2)) in the whole study population and according to the metastatic status.Results: 433 patients with a mean age of 81.2 +/- 6.0 years were included, 51% were women, 44.3% had digestive cancers, 18% breast cancer and 14.5% lung cancer and 45% metastatic cancers. Eighty-eight of these patients (20.3%) were obese at baseline. Mortality rate was 17% during the 6-month follow-up period. After adjustment for sex, gait speed, Mini-Mental State Examination, cancer site and exclusive supportive care, obesity (compared to normal weight) was independently and negatively associated with 6-month mortality only in metastatic patients (aHR 0.17, 95% CI [0.03-0.92], P = 0.04).Conclusion: our study confirms the obesity survival paradox in older cancer patients only in the metastatic group. (C) 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.

Objective To describe the characteristics of patients suffering from secondary immunodeficiencies (SID) associated with hematological malignancies (HM), who started immunoglobulin replacement therapy (IgRT), physicians' expectations regarding IgRT, and IgRT modalities. Methods Non-interventional, prospective French cross-sectional study. Results The analysis included 231 patients (66 ± 12 years old) suffering from multiple myeloma (MM) (N = 64), chronic lymphoid leukemia (CLL) (N = 84), aggressive non-Hodgkin B-cell lymphoma (aNHL) (N = 32), indolent NHL (N = 39), acute leukemia (N = 6), and Hodgkin disease (N = 6). Of the HM, 47% were currently treated, 42% were relapsing or refractory, 23% of patients had received an autologous hematopoietic stem-cell transplant, and 1% had received an allograft. Serum immunoglobulin trough levels in 195 individuals were less than 5 g/L in 68.7% of cases. Most patients had a history of recurrent infections. Immunoglobulin dose was about 400 mg/kg/mo. Half of patients started with subcutaneous infusion. When starting IgRT, physicians mainly expected to prevent severe and moderate infections. They also anticipated improvement in quality of life and survival which is beyond evidence-based medicine. Conclusion NHL is a frequent condition motivating IgRT besides well-recognized indications. Physicians mainly based the decision of starting IgRT on hypogammaglobulinemia and recurrence of infections but, irrespective of current recommendations, were also prepared to start IgRT prophylactically even in the absence of a history of infections.

Summary Background Most patients with chronic lymphocytic leukaemia relapse after initial therapy combining chemotherapy with rituximab. We assessed the efficacy and safety of rituximab maintenance treatment versus observation for elderly patients in remission after front-line abbreviated induction by fludarabine, cyclophosphamide, and rituximab (FCR). Methods This randomised, open-label, multicentre phase 3 trial at 89 centres in France enrolled treatment-naive and fit patients aged 65 years or older with chronic lymphocytic leukaemia without del(17p). Eligible patients had an Eastern Cooperative Oncology Group performance status of 0–1 and adequate renal and hepatic function. Patients in response to complete induction treatment with four monthly courses of full-dose FCR with two interim rituximab doses on day 14 of cycles 1 and 2 (oral fludarabine [40 mg/m 2 per day] and oral cyclophosphamide [250 mg/m 2 per day] for the first 3 days of each cycle, rituximab at 375 mg/m 2 intravenously on day 0 of cycle 1 and subsequently at 500 mg/m 2 on day 14 of cycle 1, days 1 and 14 of cycle 2, and day 1 of cycles 3 and 4) were eligible for randomisation. Recovery from FCR toxicity and patient willingness to continue the trial were mandatory. We randomly assigned (1:1) patients to either receive intravenous rituximab (500 mg/m 2 ) every 8 weeks for up to 2 years or undergo observation, with a central computer-generated randomisation list using randomly permuted blocks of variable sizes. Randomisation was stratified by IGHV mutational status, the presence or absence of del(11q), and response level to induction treatment. The primary endpoint was progression-free survival, with the objective to assess the superiority of rituximab maintenance relative to observation. The final analysis was done in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug in the rituximab group and in all patients in the observation group. This trial is closed to accrual whilst continuing patient follow-up. The study is registered with ClinicalTrials.gov, number NCT00645606. Findings Between Dec 14, 2007, and Feb 18, 2014, 542 patients were enrolled, of whom 525 started FCR induction. Between June 10, 2008, and Aug 14, 2014, 409 (78%) patients were randomly assigned to rituximab maintenance (n=202) or observation (n=207). Four (2%) patients in the rituximab group did not receive the allocated treatment (progressive disease [n=1], adverse events [n=3]). After a median follow-up of 47·7 months (IQR 30·4–65·8), median progression-free survival in the rituximab group (59·3 months, 95% CI 49·6–not estimable) was improved compared with the observation group (49·0 months, 39·9–60·5; hazard ratio 0·55, 95% CI 0·40–0·75; p=0·0002). Neutropenia and grade 3–4 infections were more common with rituximab maintenance (105 [53%] of 198 patients vs 74 [36%] of 207 patients and 38 [19%] vs 21 [10%], respectively) during the study. The most common grade 3–4 infection was lower respiratory tract infection (24 [12%] vs eight [4%]). The incidence of second cancers, except basal cell carcinoma, was similar in both groups (29 [15%] vs 23 [11%]). Deaths were related to adverse events for 23 (11%) patients in the rituximab group and 16 (8%) in the observation group. Interpretation 2-year maintenance rituximab in selected elderly patients improves progression-free survival and shows an acceptable safety profile. Immunotherapy maintenance strategy is a relevant option in front-line treatment of chronic lymphocytic leukaemia, even in the age of targeted therapy. Funding French National Cancer Institute (INCa), Roche, Chugai.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an ongoing global pandemic. Phase III trials have demonstrated excellent efficacies of mRNA vaccines against SARS-CoV-2 in large population studies (Baden LR, NEJM, 2021; Polack FP, NEJM, 2020). Immunosuppressed individuals such as chronic lymphocytic leukemia (CLL) patients are at risk for a suboptimal response to 2 vaccine doses (Herishanu Y, Blood, 2021). The French National Authority for Health recommends the use of a third dose in immunosuppressed patients. However, seroconversion rate after the triple-dose vaccine is not yet known. The objective of our study was to evaluate SARS-CoV-2 antibody responses after the first, second and third doses of the BNT162b2 and mRNA-1273 vaccines. Data were collected from 17 French Innovative Leukemia Organization (FILO) investigating centers and the French CLL patients' association (SILLC). SARS-CoV-2 IgG anti-Spike levels were measured at 4-6 weeks after each vaccine dose. A total of 530 patients and 14 controls were included in the study. Vaccine response was evaluated post-dose 1 for 158 CLL patients, post-dose 2, for 506 patients and post-dose 3 for 66 patients. Peripheral blood lymphocyte subsets were studied post-dose 2 by flow cytometry in 80 CLL patients and 14 controls. The median age of the patients was 71 years (range 37-93), 218 (40%) were treatment-naïve (TN), 136 (26%) had a prior CLL treatment and 176 (34%) were on therapy. Post-dose 1, the global response rate was 27% (43/158). TN patients had a response rate of 34% (23/67), similar to those who had a prior CLL treatment (33%,12/36), and higher compared to on-therapy patients (15%, 8/55, P=0.02). Post-dose 2, the global response rate was 52% (265/506). TN patients had the highest response rate of 72% (151/210) compared to previously treated patients, mostly by immunochemotherapy (60%, 78/130, P=0.02) and on-therapy patients (22%, 36/166, P65 years (OR 0.55, 95% CI 0.33-0.92, P=0.02), ongoing CLL treatment (OR 0.13, 95% CI 0.07-0.23, P Flow cytometry results suggest a differential balance of the T CD4+ cell subpopulations in Binet stage A and in patients on targeted therapy compared to healthy controls. Post-dose 2 seronegative patients were proposed a third dose and to date, 66 have been tested for the antibody response 4-6 weeks post-dose 3. The post-dose 3 response rate was 42% (28/66). TN patients and previously treated patients had a significantly higher response rate (57%, 16/28) compared to on-therapy patients (32%, 12/38, P=0.03). We further analyzed patients tested post-dose 2 with the Abbott Architect SARS-CoV-2 IgG anti-Spike assay (n=24). Those who achieved seroconversion after the third dose (n=10) had significantly higher titers post-dose 2 (median 12, IQR 3.0-40.8) compared to those who remained seronegative (n=14) (median 2.2, IQR 0.5-5.1, p An additional cohort of 40 CLL patients who presented a SARS-CoV-2 infection prior to vaccination participated to the study and was analyzed independently. All patients achieved seroconversion after infection and a single dose of vaccine, even though 30% (n=12) had an ongoing CLL treatment. In conclusion, double-dose mRNA vaccination generated a humoral response in 52% of our CLL cohort and a third dose induced seroconversion in 42% of the patients who remained seronegative after the second dose. The major independent predictor of negative antibody response was ongoing treatment with BTKi. The strongest boost to immune response against the virus seems to be SARS-CoV-2 infection, as a substantial increase in anti-Spike antibodies was observed in all CLL patients with prior infection, after a single dose vaccination. Figure 1 Figure 1. Disclosures Letestu: Janssen: Research Funding, Speakers Bureau; Roche: Speakers Bureau; AbbVie: Research Funding, Speakers Bureau. Dartigeas: Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress. Laribi: Astellas Phama, Inc.: Other: Personal Fees; BeiGene: Other: Personal Fees; AstraZeneca: Other: Personal Fees; IQONE: Other: Personal Fees; AbbVie: Other: Personal Fees, Research Funding; Takeda: Other: Personal Fees, Research Funding; Novartis: Other: Personal Fees, Research Funding; Le Mans Hospital: Research Funding; Jansen: Research Funding. Cymbalista: Lilly-LOXO: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; ASTRA ZENECA: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees.

With the emergence of targeted therapies, defining the best strategy for the treatment of previously untreated CLL patients remains challenging. The aim of this phase 2 study was to compare the efficacy of an association with ibrutinib and venetoclax (IV) to the standard FCR regimen in fit patients with intermediate risk CLL defined by either unmutated IGHV status, 11q deletion or complex karyotype in the absence of TP53 abnormality. Patients were randomized 1:1 between two treatment arms, ie FCR 6 cycles or IV. After a lead-in phase of ibrutinib as a single agent from month (M)1 to M3, the total duration of treatment with IV was based on the response achieved at M9; if bone marrow (BM) MRD was < 0.01% using flow cytometry, the treatment was continued for 6 additional months until M15 and then stopped; if BM MRD at M9 was ≥ 0.01%, the treatment with IV was continued for 18 additional months until M27. The primary endpoint was the percentage of patients with BM MRD < 0.01% at M27 in both arms. We present here the preliminary results on the first evaluation done at M9 including CT-scan, BM biopsy and MRD assessment in PB and BM after the inclusion of all the 120 patients as initially planned. One hundred and twenty patients were enrolled from September 2019 to February 2021. The median age was 59 [34-72] and 61 [34-74] years in the FCR and IV arms, respectively. The characteristics of the patients were well balanced between the 2 arms in terms of gender (male 72% FCR, 74% IV), PS ECOG 0-1 (59% FCR, 68% IV) and Binet stage (A, B and C 15%, 64%, 21% for FCR ; 8.5%, 59% and 32% for IV). No major difference in terms of cytogenetic features was noted, all patients but one had unmutated IGHV. At the time of data cut-off for this interim analysis, the median follow-up for the all cohort was 11 [2.9 - 19.8] months. The frequency of all grades adverse events (AE) observed so far was 53% (grade 3-4, 24%) in the FCR arm and 47% (grade 3-4, 17%) in the IV arm. The rate of infusion-related reactions (IRR) in the FCR arm was 35% on cycle 1-day 1 (14% grade 3-4) ; for the IV arm, 6% of patients experienced tumor lysis syndrome (TLS) (grade 4 for 4 patients). ibrutinib doses were reduced for 7 patients (4 permanently stopped and 3 resumed at a lower dose because of toxicities (digestive, hepatic or haematological)). Venetoclax was permanently discontinued before M9 in 4 patients (digestive toxicities and grade 4 neutropenia). Forty serious adverse events were reported of which 15 in the IV arm (1 sudden death, 1 ischemic stroke, 2 atrial fibrillations, 2 clinical TLS, 1 hepatitis, 1 neutropenia, 4 COVID pneumonitis and one osteoporotic fracture) and 25 in the FCR arm (2 neutropenias, 1 anemia, 1 thrombocytopenia, 1 autoimmune haemolytic anemia, 3 IRR, 4 TLS, 2 COVID pneumonitis, 4 fever episodes of undetermined origin, 1 community-acquired pneumonia, 1 gastrointestinal toxicity, 1 confusion, 2 chest pains, 1 acute myeloid leukemia, 1 myelodysplasic syndrome). The patients with COVID pneumonitis had a favorable evolution with the need for intensive care and convalescent plasma for 3 of them. The first 60 patients included in the study have reached M9 and among them, 6 prematurely discontinued the study, 3 in each arm (active hemolysis, ischemic stroke and sudden death in the IV arm; 2 grade 4 hematologic toxicities and 1 early progression in the FCR arm). In the evaluated patients (n=54), 71% of patients in the FCR arm and 48% of patients in the IV arm achieved bone BM MRD < 0.01%. The complete (CR, CRi) and partial response rates were 54% and 46% in the FCR arm and 76% and 24% in the IV arm respectively. In conclusion, the preliminary results show a lower BM MRD rate in the IV arm compared to the FCR arm at M9, with a toxicity that remains significant and relatively similar between the two arms. However, BM MRD rate should improve after longer exposure to the IV combination and the analysis of the primary endpoint at M27 will be decisive in determining the best therapeutic strategy. Disclosures Quinquenel: Abbvie: Honoraria; Janssen: Honoraria; AstraZeneca: Honoraria. Laribi: Le Mans Hospital: Research Funding; Novartis: Other: Personal Fees, Research Funding; Takeda: Other: Personal Fees, Research Funding; BeiGene: Other: Personal Fees; IQONE: Other: Personal Fees; AbbVie: Other: Personal Fees, Research Funding; Astellas Phama, Inc.: Other: Personal Fees; AstraZeneca: Other: Personal Fees; Jansen: Research Funding. Cymbalista: Lilly-LOXO: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; ASTRA ZENECA: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Leblond: AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Lilly: Consultancy; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Roche: Honoraria; Amgen: Honoraria; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dartigeas: Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress. Ferrant: Janssen: Other: Travel, Accommodations, Expenses; AbbVie: Honoraria, Other: Travel, Accommodations, Expenses; AstraZeneca: Honoraria. de Guibert: Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria. Feugier: Astrazeneca: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Honoraria; Janssen: Consultancy, Honoraria. Cartron: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria. Ysebaert: Abbvie, AstraZeneca, Janssen, Roche: Other: Advisory Board, Research Funding.

Background An accurate estimate of the duration of atrial fibrillation (AF) is critical for its safe and successful management. We examined the ability of midregional pro–atrial natriuretic peptide (MR-proANP) to identify patients presenting with AF of ≤48 vs >48 h in duration. Methods We prospectively studied 106 patients presenting with AF of known duration. We examined the predictive values of MR-proANP and N-terminal pro–brain natriuretic peptide (NT-proBNP) in the detection of recent-onset AF, in addition to other factors identified by multiple variable analyses. Results In patients presenting with AF of ≤48 vs >48 h in duration, the median MR-proANP plasma concentration was 147.7 [95.3–197.4] pmol/L vs 220.4 [154.0–303.1] pmol/L (P Conclusions A score based on a model including heart rate, dyspnea, and plasma MR-proANP concentration was helpful in identifying AF of ≤48 h in duration.

Mutational analyses performed following acquired ibrutinib resistance have suggested that chronic lymphocytic leukemia (CLL) progression on ibrutinib is linked to mutations in Bruton tyrosine kinase (BTK) and/or phospholipase Cγ2 (PLCG2) genes. Mutational information for patients still on ibrutinib is limited. We report a study aimed to provide a “snapshot” of the prevalence of mutations in a real-life CLL cohort still on ibrutinib after at least 3 years of treatment. Of 204 patients who initiated ibrutinib via an early-access program at 29 French Innovative Leukemia Organization (FILO) centers, 63 (31%) were still on ibrutinib after 3 years and 57 provided a fresh blood sample. Thirty patients had a CLL clone ≥0.5 × 109/L, enabling next-generation sequencing (NGS); BTK and PLCG2 mutations were detected in 57% and 13% of the NGS samples, respectively. After median follow-up of 8.5 months from sample collection, the presence of a BTK mutation was significantly associated with subsequent CLL progression (P = .0005 vs no BTK mutation). Our findings support that mutational analysis should be considered in patients receiving ibrutinib who have residual clonal lymphocytosis, and that clinical trials are needed to evaluate whether patients with a BTK mutation may benefit from an early switch to another treatment.

In patients with chronic lymphocytic leukaemia, achievement of a complete response with minimal residual disease of less than 0·01% (ie,1 chronic lymphocytic leukaemia cell per 10 000 leukocytes) in bone marrow has been associated with improved progression-free survival. We aimed to explore the activity of induction therapy for 9 months with obinutuzumab and ibrutinib, followed up with a minimal residual disease-driven therapeutic strategy for 6 additional months, in previously untreated patients.We did a single-arm, phase 2 trial in 27 university hospitals, general hospitals, and specialist cancer centres in France. Eligible patients were at least 18 years old and previously untreated, and had immunophenotypically confirmed B-cell chronic lymphocytic leukaemia; an Eastern Cooperative Oncology Group (ECOG) performance status score of less than 2; a Binet stage C according to IWCLL 2008 criteria or Binet stage A and B with active disease; no 17p deletion or absence of p53 mutation; and were considered medically fit. In the first part of the study (induction phase), all participants received eight intravenous infusions of obinutuzumab 1000 mg over six 4-weekly cycles and oral ibrutinib 420 mg once per day for 9 months. In part 2, after assessment on day 1 of month 9, patients with a complete response and bone marrow minimal residual disease of less than 0·01% received only oral ibrutinib 420 mg once per day for 6 additional months. Patients with a partial response, or with a complete response and bone marrow minimal residual disease of 0·01% or more, received 6 months of four 4-weekly cycles of intravenous fludarabine, cyclophosphamide, and obinutuzumab 1000 mg, alongside continuing ibrutinib 420 mg once per day. The primary endpoint was the proportion of patients achieving a complete response with bone marrow minimal residual disease less than 0·01% on day 1 of month 16 assessed by intention to treat (ITT). This trial is registered with ClinicalTrials.gov (number NCT02666898) and is still open for follow-up.Between Oct 27, 2015, and May 16, 2017, 135 patients were enrolled. After induction treatment (day 1 of month 9), 130 patients were evaluable, of which ten (8%) achieved a complete response with bone marrow minimal residual disease of less than 0·01% and were assigned to ibrutinib, and 120 (92%) were assigned to ibrutinib plus fludarabine, cyclophosphamide, and obinutuzumab. After minimal residual disease-guided treatment (day 1 of month 16), 84 (62%, 90% CI 55-69) of 135 patients (ITT population) achieved a complete response with bone marrow minimal residual disease of less than 0·01%. The most common haematological adverse event was thrombocytopenia (in 45 [34%] of 133 patients at grade 1-2 in months 1-9 and in 43 [33%] of 130 patients at grade 1-2 in months 9-15). The most common non-haematological adverse events were infusion-related reactions (in 83 [62%] patients at grade 1-2 in months 1-9) and gastrointestinal disorders (in 62 [48%] patients at grades 1 and 2 in months 9-15). 49 serious adverse events occurred, most frequently infections (ten), cardiac events (eight), and haematological events (eight). No treatment-related deaths occurred.Obinutuzumab and ibrutinib induction therapy followed by a minimal residual disease driven strategy is safe and active in patients with previously untreated chronic lymphocytic leukaemia. With longer follow-up, including assessing the evolution of minimal residual disease, if response is maintained, this strategy could be an option in the first-line setting in patients with chronic lymphocytic leukaemia, although randomised evidence is needed.Roche, Janssen.

Mutational analyses performed following acquired ibrutinib resistance have suggested that chronic lymphocytic leukemia (CLL) progression on ibrutinib is linked to mutations in Bruton tyrosine kinase (

Waldenstrom's macroglobulinemia is generally treated with alkylating agents, purine analogs and monoclonal antibodies, alone or in combination. We report the outcomes of 82 patients (median age 61 years) treated with the RFC combination. Twenty-five patients were treatment-naive. RFC was administered every 4 weeks, for a median of five cycles. At treatment discontinuation, the overall response rate was 85.4%. The responses improved after treatment discontinuation in 25 patients, with a median time to best response achievement of 10.8 months, raising the major response rate (PR, VGPR and CR) from 64.6% to 76.8%. With a median follow-up of 47 months, the median progression-free survival time had not been reached (67% PFS at 48 months) and was influenced by age and treatment status before RFC. Likewise, the median time to next therapy had not been reached. Two cases of myelodysplastic syndrome/AML and 3 cases of transformation to aggressive lymphoma occurred. Thirteen patients died. The 3-year overall survival rate was 90%. Long-lasting cytopenias occurred in 19 patients. The RFC combination thus gave a high response rate and durable responses, even in heavily treatment-experienced patients. The high incidence of long-lasting cytopenia might be reduced by giving fewer courses and thereby minimizing myelotoxicity. Am. J. Hematol. 91:782-786, 2016. © 2016 Wiley Periodicals, Inc.

// Stephane Saint-Georges 1,2 , Maude Quettier 1,2 , Marouane Bouyaba 3 , Stephanie Le Coquil 1,2 , Vanessa Lauriente 1,2 , Lionel Guittat 1,2 , Vincent Levy 3 , Florence Ajchenbaum-Cymbalista 1,2,4 , Nadine Varin-Blank 1,2 , Christine Le Roy 1,2,* and Dominique Ledoux 1,2,* 1 INSERM U978, Bobigny, France 2 Universite Paris 13, Sorbonne Paris Cite, Labex “Inflamex”, Bobigny, France 3 Assistance Publique-Hopitaux de Paris, Hopital Avicenne, Unite de Recherche Clinique, Bobigny, France 4 Assistance Publique-Hopitaux de Paris, Hopital Avicenne, Service d’Hematologie Biologique, Bobigny, France * These authors are co-senior authors Correspondence to: Christine Le Roy, email: // Nadine Varin-Blank, email: // Keywords : CLL, lymphadenopathy, B-cell receptor, CXCR4/CXCR5, protein kinase D Received : December 23, 2015 Accepted : April 16, 2016 Published : April 26, 2016 Abstract In Chronic Lymphocytic Leukemia (CLL), infiltration of lymph nodes by leukemic cells is observed in patients with progressive disease and adverse outcome. We have previously demonstrated that B-cell receptor (BCR) engagement resulted in CXCR4 down-regulation in CLL cells, correlating with a shorter progression-free survival in patients. In this study, we show a simultaneous down-regulation of CXCR4, CXCR5 and CD62L upon BCR triggering. While concomitant CXCR4 and CXCR5 down-regulation involves PKDs, CD62L release relies on PKC activation. BCR engagement induces PI3K-δ-dependent phosphorylation of PKD2 and 3, which in turn phosphorylate CXCR4 Ser 324/325 . Moreover, upon BCR triggering, PKD phosphorylation levels correlate with the extent of membrane CXCR4 decrease. Inhibition of PKD activity restores membrane expression of CXCR4 and migration towards CXCL12 in BCR-responsive cells in vitro . In terms of pathophysiology, BCR-dependent CXCR4 down-regulation is observed in leukemic cells from patients with enlarged lymph nodes, irrespective of their IGHV mutational status. Taken together, our results demonstrate that PKD-mediated CXCR4 internalization induced by BCR engagement in B-CLL is associated with lymph node enlargement and suggest PKD as a potential druggable target for CLL therapeutics.

BACKGROUND: We decided to evaluate the evolution of vulnerability in breast cancer survivors receiving an individualized survivorship care plan and living in an area (Seine-Saint-Denis, SSD), which is among the poorest in France with a median household income is 68% lower than in Paris. In SSD, cancer is the leading cause of premature mortality. Whereas it is widely admitted in France that 25% of patients are faced with financial difficulties after breast cancer, this proportion reaches 40% in SSD. PATIENTS AND METHODS: Ac'Santé93 is a non-profit organization whose aim is to provide supportive care, health education and individualized assistance to patients and families, and to facilitate timely access to quality medical and psychosocial care. Vulnerability was evaluated using a 11-item standardized score (EPICES) previously investigated by French Health Examination Centers. Strictly speaking this score was aimed at measuring precarity, a concept referring to a social condition assumed to face worsening. This score is more strongly related to health status than the administrative classification of poverty (Sass, Sante Publique 2006). Vulnerability was defined by a score ≥30 and considered as severe when ≥40. In SSD two thirds of the population are affected by vulnerability. Patients included in the study were scored after cancer diagnosis (E1) and 6 mos. after the first evaluation (E2). Patients were divided into tertiles according to E1: 30-40, 40-67 and 67-100. Psychosocial comorbidities, demographic data, and supportive care received were also recorded. Actions undertaken were divided in three categories: social/advocacy (e.g. help with filling out administrative forms), individual (e.g. dietician consultation) and group (e.g. group sessions led by a sport instructor). RESULTS: Over the year 2014, 120 breast cancer survivors were included and had E1 and E2 scores. Median E1 and E2 were 52.1 and 47.3 and the mean difference was 7.2 (p CONCLUSION: Survivorship care plans can improve vulnerability in most pts. Paradoxically, it seems easier to improve vulnerability in pts with highest initial scores. Furthermore these patients are those who benefit the most from support groups. We hypothesize that desocialization is frequently underestimated in this population, and that support groups, besides their primary goal, act through developing social links. Finally, the finding that younger patients are at higher risk for worsening vulnerability underscores the burden of unmet needs in youngest breast cancer survivors. Citation Format: Jaouen A, Festa A, Boubaya M, Levy V, Zelek L. How can we improve vulnerability score in breast cancer survivors? A pilot experience in an underprivileged community. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-12-12.