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International audience; Prolonged Covid-19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in-hospital stay (LOS) due to Covid-19 among patients with lymphoma and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid-19 to 16 French hospitals in March and April, 2020 were included. Length of in-hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19–92). Ninety-four patients (85%) had B-cell non-Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid-19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti-CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1–235). After a median follow-up of 191 days (3–260), the 6-month overall survival was 69%. In multivariable analyses, recent administration of anti-CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42–3.6, p < 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04–4.52, p = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti-CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid-19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population.

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 60 years of age) with untreated primary CNS lymphoma (PCNSL) were randomly assigned upfront to receive WBRT (Arm A) or ASCT (Arm B) as consolidation treatment after an induction chemotherapy consisting of two cycles of R-MBVP (rituximab, methotrexate, VP16, BCNU, prednisone) followed by two cycles of R-AraC (rituximab, cytarabine). Intensive chemotherapy consisted of thiotepa (250 mg/m2/d D9; D8; D7), busulfan (8 mg/kg D6 through D4), and cyclophosphamide (60 mg/kg/d D3; D2). WBRT delivered 40 Gy (2 Gy/ fraction). Cognitive functions were prospectively assessed until disease progression and focused on global cognitive function, episodic verbal memory, attention and mental flexibility, and psychoaffective status. Results: 140 patients were randomized (Arm A: N = 70; Arm B: N = 70). Fifty-three and 44 patients completed WBRT and ASCT respectively (per protocol population), including 3 and 5 patients who were in progressive disease (PD) at time of WBRT and ASCT, respectively. 8-y EFS from time of consolidation in the per protocol population was 75.9% [63.3-91.0] and 39.9% [26.8-59.3] after ASCT and WBRT, respectively (p = 0.007) (fig 1a). The risk of relapse was significantly decreased after ASCT compared to WBRT (8-y relapse-free interval 94.1% [86.4-100] vs 47.6% [34.2-66.3], (p Causes of deaths after WBRT (n = 17) were PD (n = 12), neurotoxicity (n = 3), second-line ASCT (n = 2). After ASCT, causes of deaths (n = 14) were treatment-related death (n = 5, including 2 occurring > 100 days post-ASCT, and 2 in patients in PD before ASCT), PD (n = 4), neurotoxicity following salvage WBRT (n = 1), second solid cancer (n = 3) and undetermined in one patient. In multivariate analysis, ECOG, disease status at the end of induction, and protein level in the CSF at diagnosis were independent prognostic factors for OS. Disease status at the end of induction and intraocular involvement at diagnosis were independent prognostic factors for EFS. Cognitive decline that could be fatal was only observed in patients who received WBRT. Imaging analysis of post consolidation leukoencephalopathy is ongoing. Conclusions: Consolidation with ASCT after HD-MTX based induction chemotherapy resulted in an excellent disease control but with a higher treatment-related mortality than WBRT. Severe Cognitive decline and late treatment-induced neurotoxic deaths were observed after WBRT. Intensity of the thiotepa-busulfan-cyclophosphamide regimen used before ASCT should be slightly reduced to improve the benefit/risk ratio of ASCT in first-line treatment of young patients with PCNSL. Figure 1 Figure 1. Disclosures Sylvain: Sanofi, Celegene, Roche, Abbvie, Sandoz, Janssen, Takeda: Consultancy. Damaj: takeda: Consultancy, Honoraria; roche: Consultancy, Honoraria. Sanhes: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Primary mediastinal B-cell lymphoma (PMBL) is a rare type of aggressive lymphoma typically affecting young female patients. The first-line standard of care remains debated. We performed a large multicenter retrospective study in 25 centers in France and Belgium to describe PMBL patient outcomes after first-line treatment in real-life settings. A total of 313 patients were enrolled and received rituximab (R) plus ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone) (n = 180) or CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) delivered every 14 days (R-CHOP14, n = 76) or 21 days (R-CHOP21, n = 57) and consolidation strategies in modalities that varied according to time and institution, mainly guided by positron emission tomography. Consolidation autologous stem cell transplantation was performed for 46 (25.6%), 24 (31.6%), and 1 (1.8%) patient in the R-ACVBP, R-CHOP14, and R-CHOP21 groups, respectively (P < .001); only 17 (5.4%) patients received mediastinal radiotherapy. The end-of-treatment complete metabolic response rates were 86.3%, 86.8%, and 76.6% (P = .23) in the R-ACVBP, R-CHOP14, and R-CHOP21 groups. The median follow-up was 44 months, and the R-ACVBP, R-CHOP14, and R-CHOP21 three-year progression-free survival probabilities were 89.4% (95% confidence interval [CI], 84.8-94.2), 89.4% (95% CI, 82.7-96.6), and 74.7% (95% CI, 64-87.1) (P = .018). A baseline total metabolic tumor volume (TMTV) ≥360 cm3 was associated with a lower progression-free survival (hazard ratio, 2.18; 95% CI, 1.05-4.53). Excess febrile neutropenia (24.4% vs 5.3% vs 5.3%; P < .001) and mucositis (22.8% vs 3.9% vs 1.8%; P < .001) were observed with R-ACVBP compared with the R-CHOP regimens. Patients with PMBL treated with dose-dense immunochemotherapy without radiotherapy have excellent outcomes. R-ACVBP acute toxicity was higher than that of R-CHOP14. Our data confirmed the prognostic importance of baseline TMTV.

Monoclonal antibodies (mAbs) against programmed cell death 1 (PD-1), such as nivolumab and pembrolizumab, are associated with high response rates in patients with relapsed or refractory classic Hodgkin lymphoma (HL). To date, no prognostic factor for overall survival (OS) has been established with these agents in HL. We examined whether the first early response assessment evaluated using 18F-FDG PET/CT may be associated with OS in this setting. Methods: This retrospective study included 45 patients from 34 institutions. In a masked, centralized review, 3 independent radiologists classified PET/CT scans obtained at a median of 2.0 mo (interquartile range, 1.7-3.7 mo) after nivolumab initiation using existing criteria (i.e., 2014 Lugano classification and 2016 LYRIC). Patients were classified according to 4 possible response categories: complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (NMR), or progressive metabolic disease (PMD). Because the OS of patients with NMR and PMR was similar, they were grouped together. OS was estimated using the Kaplan-Meier method and compared between groups using log-rank testing. Results: Eleven patients (24%) died after a median follow-up of 21.2 mo. The classification was identical between Lugano and LYRIC because all 16 progression events classified as indeterminate response per LYRIC were confirmed on subsequent evaluations. Both Lugano and LYRIC classified patients as CMR in 13 cases (29%), PMD in 16 (36%), NMR in 4 (9%), and PMR in 12 (27%). The 2-y OS probability was significantly different in patients with PMD (0.53; 95% confidence interval [95%CI], 0.32-0.87), NMR or PMR (0.80; 95%CI, 0.63-1.00), and CMR (1.00; 95%CI, 1.00-1.00) in the overall population (P = 0.02, 45 patients), as well as according to a landmark analysis at 3 mo (P = 0.05, 32 patients). Conclusion: In relapsed or refractory HL patients treated with anti-PD-1 mAbs, the first early PET/CT assessment using either Lugano or LYRIC predicted OS and allowed early risk stratification, suggesting that PET/CT might be used to develop risk-adapted strategies.

PURPOSE To determine the efficacy and toxicity of chemoimmunotherapy followed by either whole-brain radiotherapy (WBRT) or intensive chemotherapy and autologous stem-cell transplantation (ASCT) as a first-line treatment of primary CNS lymphoma (PCNSL). PATIENTS AND METHODS Immunocompetent patients (18 to 60 years of age) with untreated PCNSL were randomly assigned to receive WBRT or ASCT as consolidation treatment after induction chemotherapy consisting of two cycles of R-MBVP (rituximab 375 mg/m2 day (D) 1, methotrexate 3 g/m2 D1; D15, VP16 100 mg/m2 D2, BCNU 100 mg/m2 D3, prednisone 60 mg/m2/d D1-D5) followed by two cycles of R-AraC (rituximab 375 mg/m2 D1, cytarabine 3 g/m2/D, D1, and D2). Intensive chemotherapy consisted of thiotepa (250 mg/m2/d D9; D8; D7), busulfan (8 mg/kg D6 through D4), and cyclophosphamide (60 mg/kg/d D3; D2). WBRT delivered 40 Gy (2 Gy/fraction). The primary end point was 2-year progression-free survival. Cognitive outcome was the main secondary end point. Analysis was intention to treat in a noncomparative phase II trial. RESULTS Between October 2008 and February 2014, 140 patients were recruited from 23 French centers. Both WBRT and ASCT met the predetermined threshold (among the first 38 patients in each group, at least 24 patients were alive and disease free at 2 years). The 2-year progression-free survival rates were 63% (95% CI, 49% to 81%) and 87% (95% CI, 77% to 98%) in the WBRT and ASCT arms, respectively. Toxicity deaths were recorded in one and five patients after WBRT and ASCT, respectively. Cognitive impairment was observed after WBRT, whereas cognitive functions were preserved or improved after ASCT. CONCLUSION WBRT and ASCT are effective consolidation treatments for patients with PCNSL who are 60 years of age and younger. The efficacy end points tended to favor the ASCT arm. The specific risk of each procedure should be considered.

International audience; The treatment of primary vitreoretinal lymphoma (PVRL) remains controversial regarding the use of local, systemic, or combined treatments. The aim of this study was to analyze the efficacy and toxicity of intravenous high-dose methotrexate (IV HD-MTX) based systemic therapy in a uniformly treated population of PVRL patients. From a nationwide French database, we retrospectively selected 59 patients (median age: 70 years, median Karnofsky Performance Status: 90%) with isolated PVRL at diagnosis who received first-line treatment with HD-MTX between 2011-2018. 8/59 patients also received a local treatment. No deaths or premature discontinuations of MTX due to toxicity were reported. A complete response was obtained in 40/57 patients after chemotherapy. Before treatment, IL-10 was elevated in the aqueous humor (AH) or in the vitreous in 89% of patients. After treatment, AH IL-10 was undetectable in 87% of patients with a CR/uCR/PR and detectable in 92% of patients with PD/SD. After a median follow-up of 61 months, 41/59 (69%) patients had relapsed, including 29 isolated ocular relapses as the first relapse and a total of 22 brain relapses. The median overall survival, progression-free survival, ocular-free survival and brain-free survival were 75, 18, 29 and 73 months, respectively. IV HD-MTX based systemic therapy as a first-line treatment for isolated PVRL is feasible, with acceptable toxicity, even in an elderly population. This strategy seems efficient to prevent brain relapse with prolonged overall survival. However, the ocular relapse rate remains high. New approaches are needed to improve local control of this disease, and ocular assessment could be completed by monitoring AH IL-10.

International audience; Historically, double or triple hit lymphoma (DHL and THL) have poor outcomes with conventional chemotherapy, but there is currently no guideline. We report the French experience in managing DHL and THL in first line using collective data on both survival and tolerance. All consecutive patients with newly diagnosis of large B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements, as determined by FISH between January 2013 and April 2019 were included. Based on the eligibility criteria, 160 patients were selected among the 184 patients identified. With a median follow-up of 32 months, 2- and 4-year progression free survival (PFS) rates were 40% and 28% with R-CHOP compared with 57% and 52% with intensive chemotherapy (P = .063). There was no difference in overall survival (OS). For advanced stages, PFS was significantly longer with intensive chemotherapy than with R-CHOP (P = .029). There was no impact of autologous stem cell transplantation among patient in remission. For patients with central nervous system (CNS) involvement, the 2-year PFS and OS rate was 21% and 39%, vs 57% and 75% without CNS disease (P = .007 and P < .001). By multivariate analysis, elevated IPI score and CNS disease were strongly and independently associated with a poorer survival, whereas treatment was not significantly associated with OS. This is the largest series reporting the treatment of DHL and THL in Europe. The PFS was significantly longer with an intensive regimen for advanced stage, but no difference in OS, supporting the need for a prospective randomized trial.

Background: Patients with lymphoma are immunocompromised because of the disease per se and its treatments. We aimed to describe the characteristics of patients with lymphoma hospitalized for Coronavirus Disease 2019 (Covid-19) and to analyze pre-Covid-19 determinants of mortality. Methods: This retrospective multicentric cohort study used the Programme de Médicalisation des Systèmes d'Information database to identify all adult patients with lymphoma, hospitalized for Covid-19 in March and April 2020, in 12 hospitals of three French regions with pandemic outbreaks. The characteristics of lymphoma and Covid-19 were collected from medical charts. Findings: Eighty-nine patients were included. The median age was 67 years (range, 19–92), 66% were male and 72% had a comorbidity. Most patients had B-cell non-Hodgkin lymphoma (86%) and had received a lymphoma treatment within one year (70%). With a median follow-up of 33 days from admission, 30-day overall survival was 71%, (95% confidence interval, 62–81%). In multivariable analysis, having an age ≥ 70 years (hazard ratio 2·87, 1·20–6·85, p = 0·02) and relapsed/refractory lymphoma (hazard ratio 2·54, 1·14–5·66, p = 0·02) were associated with mortality. Recent bendamustine treatment (n = 9) was also pejorative (hazard ratio 3·20, 1·33–7·72, p = 0·01), but was strongly associated with relapsed/refractory lymphoma. Remarkably, 30-day overall survival for patients

Two autologous anti-CD19 chimeric antigen receptors (CAR) T cells (axicabtagene ciloleucel [axi-cel] and tisagenlecleucel [tisa-cel]) are commercially approved in Europe for relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). We performed a retrospective study to evaluate patterns of use, efficacy and safety for axi-cel and tisa-cel. Data from 70 patients who underwent apheresis for commercial CAR T cells between January 2018 and November 2019 in our institution were retrospectively collected. Sixty-one patients were infused. The median age at infusion was 59 years old (range 27-75 years). The median number of prior therapies was 3 (range, 2-6). The overall response rates (ORRs) at 1 month and 3 months were 63% and 45%, respectively, with 48% and 39% achieving a complete response (CR), respectively. After a median follow-up after infusion of 5.7 months, the median progression-free survival (PFS) was 3.0 months (95% CI, 2.8-8.8 months), and the median overall survival (OS) was 11.8 months (95% CI, 6.0-12.6 months). In multivariate analysis, factors associated with poor PFS were the number of previous lines of treatment before CAR T cells (≥4) (P = .010) and a C reactive protein (CRP) value30 mg/L at the time of lymphodepletion (P .001). Likewise, the only factor associated with a shorter OS was CRP30 mg/L (P = .009). Cytokine release syndrome (CRS) of any grade occurred in 85% of patients, including 8% of patients with CRS of grade 3 or higher. Immune cell-associated neurotoxicity syndrome (ICANS) of any grade occurred in 28% of patients, including 10% of patients with ICANS of grade 3 or higher. Regarding efficacy and safety, no significant difference was found between axi-cel and tisa-cel. This analysis describes one of the largest real-life cohorts of patients treated with axi-cel and tisa-cel for R/R aggressive B cell lymphoma in Europe.

Introduction: Primary mediastinal B cells lymphoma (PMBCL) is a rare subtype of aggressive non Hodgkin lymphoma (NHL). Despite therapeutic progresses, 10 to 30% of PMBCL patients are primary refractory or experience early relapses (R/R). Despite Autologous hematopoietic cell transplantation (auto-HCT) after bridging therapy or new therapies such as PD-1 inhibitors or CAR-T cells, R/R PMBL patients have a very poor outcome. Allogeneic stem cell transplantation (allo-HCT) is thus a potentially curative treatment for patients who relapsed after salvage therapies. Only limited data have been published about allo-SCT in R/R PMBCL (Herrera A. F, BBMT 2019). In the present study conducted on behalf the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) and the lymphoma study association (LYSA) group, we investigated the outcomes of allo-transplanted adult R/R PMBCL. Methods This multicenter retrospective study included all adult R/R PMBCL patients reported to the SFGM-TC and who underwent an allo-HCT between 1999 and 2018. Data have been obtained through ProMISe (internet-based system shared by all European transplantation centers) and completed by consulting the medical files of the LYSA group centers. All patients have given signed informed consent. Results Thirty-three patients with R/R PMBCL from 19 French (n=29) and 3 Belgium (n=4) centers were included. The median age at transplant was 33 y (18-61), with a predominance of female patients (58%). Majority of patients had a low HCT-CI score [0 = 9/17 (53%), data missing in 16 patients]. Seventy-six percent of patients had an IPI score between 1 and 2 and Ann Harbor score was ≥ 3 in 56.6% at diagnosis. Median number of treatment lines before allo-HCT was 3 (1-6). All patients received poly-chemotherapies with anthracyclines and anti-CD20 as first-line therapy. Most sixty-one percent of patients had previously undergone auto-HCT and one patient received CAR-T before allo-HCT. Forty one percent of patients were primary refractory. At time of transplant, 50% of patients were in complete response, 40% in partial response, and 10% had a progressive disease. Conditioning regimen was reduced intensity regimen in 63%. Stem cell source was PBSC in 88%. Donors were sibling in 42% or matched related donor in 39%. An alternative donor was chosen in 18%. GVHD prophylaxis included antithymocyte globulin in 61%, and calcineurin inhibitor in 97%. Median follow up was 78 months (3.5-157). Considering the whole cohort, 2y OS, DFS, NRM, and cumulative incidence of relapse were 48% (95%CI: 33-70), 60% (95%CI: 44-82), 18% (95%CI: 7-34), and 34% (95%CI: 18-50) respectively. Cumulative incidences of day 100 grade I-II and III-IV acute GVHD 36% and 0%, respectively. Cumulative incidence was 32% among whom 33% had an extensive cGVHD. Patients with progressive disease at transplantation had worst 2y PFS and OS (PFS: HR: 6.12, 95%CI: 1.32-28.31, p=0.02 and OS: HR: 7.04, 95%CI: 1.52-32.75, p=0.013). Conclusion: To our knowledge, this is the largest published study evaluating outcomes of allo-HCT for R/R PMBCL. Although this is a retrospective study with a limited number of patients, the outcomes suggest that allo-HCT is a therapeutic option providing durable remissions for patients with R/R PMBCL. Introduction: Primary mediastinal B cells lymphoma (PMBCL) is a rare subtype of aggressive non Hodgkin lymphoma (NHL). Despite therapeutic progresses, 10 to 30% of PMBCL patients are primary refractory or experience early relapses (R/R). Despite Autologous hematopoietic cell transplantation (auto-HCT) after bridging therapy or new therapies such as PD-1 inhibitors or CAR-T cells, R/R PMBL patients have a very poor outcome. Allogeneic stem cell transplantation (allo-HCT) is thus a potentially curative treatment for patients who relapsed after salvage therapies. Only limited data have been published about allo-SCT in R/R PMBCL (Herrera A. F, BBMT 2019). In the present study conducted on behalf the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) and the lymphoma study association (LYSA) group, we investigated the outcomes of allo-transplanted adult R/R PMBCL. Methods This multicenter retrospective study included all adult R/R PMBCL patients reported to the SFGM-TC and who underwent an allo-HCT between 1999 and 2018. Data have been obtained through ProMISe (internet-based system shared by all European transplantation centers) and completed by consulting the medical files of the LYSA group centers. All patients have given signed informed consent. Results Thirty-three patients with R/R PMBCL from 19 French (n=29) and 3 Belgium (n=4) centers were included. The median age at transplant was 33 y (18-61), with a predominance of female patients (58%). Majority of patients had a low HCT-CI score [0 = 9/17 (53%), data missing in 16 patients]. Seventy-six percent of patients had an IPI score between 1 and 2 and Ann Harbor score was ≥ 3 in 56.6% at diagnosis. Median number of treatment lines before allo-HCT was 3 (1-6). All patients received poly-chemotherapies with anthracyclines and anti-CD20 as first-line therapy. Most sixty-one percent of patients had previously undergone auto-HCT and one patient received CAR-T before allo-HCT. Forty one percent of patients were primary refractory. At time of transplant, 50% of patients were in complete response, 40% in partial response, and 10% had a progressive disease. Conditioning regimen was reduced intensity regimen in 63%. Stem cell source was PBSC in 88%. Donors were sibling in 42% or matched related donor in 39%. An alternative donor was chosen in 18%. GVHD prophylaxis included antithymocyte globulin in 61%, and calcineurin inhibitor in 97%. Median follow up was 78 months (3.5-157). Considering the whole cohort, 2y OS, DFS, NRM, and cumulative incidence of relapse were 48% (95%CI: 33-70), 60% (95%CI: 44-82), 18% (95%CI: 7-34), and 34% (95%CI: 18-50) respectively. Cumulative incidences of day 100 grade I-II and III-IV acute GVHD 36% and 0%, respectively. Cumulative incidence was 32% among whom 33% had an extensive cGVHD. Patients with progressive disease at transplantation had worst 2y PFS and OS (PFS: HR: 6.12, 95%CI: 1.32-28.31, p=0.02 and OS: HR: 7.04, 95%CI: 1.52-32.75, p=0.013). Conclusion: To our knowledge, this is the largest published study evaluating outcomes of allo-HCT for R/R PMBCL. Although this is a retrospective study with a limited number of patients, the outcomes suggest that allo-HCT is a therapeutic option providing durable remissions for patients with R/R PMBCL. Disclosures Sibon: Abbvie: Consultancy; Takeda: Consultancy; iQone: Consultancy; Roche: Consultancy; Janssen: Consultancy. Loschi: AbbVie: Ended employment in the past 24 months, Honoraria; CELGENE/BMS: Honoraria; Gilead: Ended employment in the past 24 months, Honoraria; Novartis: Ended employment in the past 24 months, Honoraria; Servier: Ended employment in the past 24 months, Honoraria; MSD: Honoraria. Dulery: Novartis: Honoraria; Takeda: Consultancy; Gilead: Other: Travel support and registration fees for scientific meetings .

Methods : This multicentric retrospective study aimed to evaluate the efficacy and the safety of the combination of BBV in patients with non-cutaneous R/R PTCL among 21 LYSA centers in France and Belgium. The primary objective was to evaluate the best overall response rate (ORR) (complete response (CR) and partial response (PR)). Secondary objectives were progression free survival (PFS), overall survival (OS), duration of response (DoR), impact of transplantation on outcome, and safety. Patients treated between January 2013 and October 2020 were reviewed and all the data were collected through an electronic questionnaire sent to all the physicians. Results : Eighty two patients with R/R PTCL (40 angioimmunoblastic lymphoma (AITL), 2 T-cell lymphoma with TFH phenotype ,13 PTCL not otherwise specified (PTCL NOS), 5 Alk+ anaplastic large cell lymphoma (ALCL), 17 Alk- ALCL, , 1 Extranodal NK-/T-cell lymphoma, 3 Enteropathy-associated T-cell lymphoma (EATL), 1 subcutaneous panniculitis) were included. Median age at beginning of BBV was 60 years, most of patients were male (61%), had advanced stage (88%) and an IPI ≥ 2 (79%). Half of patients were refractory to their last treatment. Median number of prior regimens was 1 (range 1 to 6). The best ORR was 71%, with 51% of patients in CR. In multivariable analysis, only the relapse status after the last regimen (relapse vs refractory) was associated with ORR, relapsed patients having a better ORR (83% vs 57% in refractory patients, p=.014, OR=3.70 (95%CI:1.3-10.5)). Median DoR was 15.4 months in patients with CR but differed significantly whether patients were transplanted or not (Not reached vs 8.4 months, p=.0055). Twenty-two patients (30% of patients ≤ 70 years of age) were transplanted (6 autologous and 16 allogenic). With a median follow-up of 9 months, the median PFS and OS were 8.3 and 26.3 months respectively. In multivariable analysis, only 2 factors had a significant impact on PFS and OS: best response (CR/PR vs SD/PD with a median PFS of 17.4 vs 1.9 months, p Fifty-nine percent of patients experienced a grade 3 to 4 adverse event which was mainly hematologic toxicity. Treatment had to be stopped in 11% of patients. Conclusion: To the best of our knowledge, this is the first study reporting on the combination of BBV in the treatment of R/R PTCL in such a large cohort. The results are very encouraging with a high response rate, long DoR in responding patients and a very good outcome. Furthermore, patients in CR who are eligible for transplant have the best outcome, making this combination a good candidate as salvage therapy before transplant consolidation in these high-risk lymphomas with limited treatment options. Figure 1 Figure 1. Disclosures Bouabdallah: Kite/Gilead: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Herbaux: Takeda: Honoraria, Research Funding; Janssen: Honoraria; Roche: Honoraria; Abbvie: Honoraria, Research Funding. Brice: MSD: Research Funding; Amgen: Other: Travel/accommodations/expenses; Roche: Other: Travel/accommodations/expenses; Takeda: Research Funding. Sibon: Abbvie: Consultancy; Janssen: Consultancy; Roche: Consultancy; iQone: Consultancy; Takeda: Consultancy. Laribi: AstraZeneca: Other: Personal Fees; AbbVie: Other: Personal Fees, Research Funding; IQONE: Other: Personal Fees; Astellas Phama, Inc.: Other: Personal Fees; BeiGene: Other: Personal Fees; Takeda: Other: Personal Fees, Research Funding; Novartis: Other: Personal Fees, Research Funding; Le Mans Hospital: Research Funding; Jansen: Research Funding. Damaj: roche: Consultancy, Honoraria; takeda: Consultancy, Honoraria. OffLabel Disclosure: Brentuximab Vedotin and Bendamustine

Monoclonal antibodies targeted against the immune checkpoint molecules CTLA-4 and PD-1 have recently obtained approval for the treatment of metastatic melanoma and advanced/refractory non small-cell lung cancers and metastatic renal cancer. Besides their efficacy profile, these immune targeted agents also generate immune-related adverse events that may be life threatening if not anticipated and managed appropriately. This new family of dysimmune toxicities remains largely unknown to the broad oncology community. We propose here some practical guidelines for the oncologist to help in the clinical care of patients under immune checkpoint molecules.

Background : AETHERA randomized controlled study (Moskowitz, Lancet 2015) showed that the administration of Brentuximab Vedotin (BV) maintenance after autologous stem cell transplantation (ASCT) improved progression free survival (PFS) in BV-naive refractory/relapsed (R/R) Hodgkin lymphoma (HL) patients. However, since BV approval for R/R HL in 2012, many patients are receiving salvage BV before ASCT, alone or combined with chemotherapy. In the AMAHRELIS retrospective nationwide French study, we investigated the real-life outcome of patients with R/R HL mostly treated with BV-based salvage therapies and who received post-ASCT BV maintenance. Objectives : As primary 0objective, we assessed 2 years-PFS of patients treated with post-ASCT BV maintenance from 2012 to 2017 in France. As secondary objectives, we correlated variables (such as use of salvage BV before ASCT, centrally reviewed TEP-assessed response) with survival, and evaluated reported tolerance of BV using the CTCAE v4.0 criteria. Methods : We conducted this observational retrospective study in 58 national centers. Inclusion criteria were R/R HL patients who received at least two infusions of BV after ASCT, at the exclusion of patients in progression after transplant. Among 1134 patients who underwent ASCT for R/R HL between 2012 and 2017 in France based on the French society of bone marrow transplantation database, 835 (74%) patients were screened and data were available for 794 (70%) patients. FDG-PET scan at relapse and before transplantation were recorded and centrally reviewed (still ongoing). FDG-PET scan were reported using the Deauville score (DS), and complete remission was defined by a DS < 4. Post-transplant status was evaluated based on CT-scan or on FDG-PET scan results. This study was approved by the SFGMTC and the LYSA. Results : Fifteen percent (115/794) of patients met eligibility criteria, and were enrolled in this study. Among them, 95% met inclusion criteria for BV maintenance according to the AETHERA study as primary refractory disease (43%), early relapse (27%) or extranodal disease (49%). The mean number of BV injections after ASCT was 11 (3-18). Patients characteristics were : mean age was 34 y (range between 16-70y), 54% were male, and 57% of patients were stage III or IV at relapse. Notably, 70% of patients received BV as salvage therapy and 81% achieved a complete remission before ASCT. The median follow-up period was 35 months. The 2 years survival for the whole cohort was 75,3% for PFS (95% CI : 68,4-84,3) and 96,4% for overall survival (95% CI : 94,2-100) (Figure 1). The use of BV as part of salvage therapy before transplant had no impact on PFS. We observed a trend to an increased occurrence of neuropathy in patients receiving BV before transplant without impact on early treatment discontinuation. We tested several variables for correlation with survival using a univariate Cox model including high risk patients defined as primary refractory disease or early relapse and disseminated disease, extranodal relapse, use of BV before transplant, number of salvage lines, remission status before and after transplant (complete response versus partial response or stable disease), time between ASCT and BV onset and number of BV cycles after transplant. Among these variables, high risk status, less than 10 post transplant BV cycles and absence of post transplant complete remission significantly correlated with a reduced survival probability, and remained significant after analysis using a multivariate Cox model (Table 1). Conclusion : From the real-life AMAHRELIS study, we confirmed the very good outcome of R/R HL patients in the era of post-transplant BV maintenance, with a 2y-PFS of 75% similar to the results of the AETHERA landmark study (2y-PFS of 63%). The results of current strategies with pre- and post-transplant BV outperformed historical series based on high dose therapies, including those of tandem transplant for high risk patients. Future studies incorporating BV strategies with immune checkpoint inhibitors might improve outcome in R/R HL patients. Disclosures Meignan: ROCHE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Sibon:takeda france: Consultancy. Stamatoulas Bastard:Pfizer: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Celgene: Honoraria; Takeda: Consultancy. Fornecker:Takeda: Consultancy; Roche: Consultancy. Casasnovas:Takeda: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Roche: Consultancy, Honoraria, Other: travel, accomodations, expenses, Research Funding; Gilead: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Abbvie: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Cartron:Gilead: Honoraria; Jansen: Honoraria; Abbvie: Honoraria; Celgene: Consultancy, Honoraria; Sanofi: Honoraria; F. Hoffmann-La Roche: Consultancy, Honoraria. Ghesquieres:Gilead: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; CELGENE: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Roche: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Janssen: Honoraria. Brice:Takeda: Consultancy; Roche: Consultancy. Hermine:AB Science: Consultancy, Current equity holder in publicly-traded company, Honoraria, Patents & Royalties, Research Funding; Celgene BMS: Consultancy, Research Funding; Roche: Consultancy; Novartis: Research Funding; Alexion: Research Funding. Rubio:Medac: Consultancy; Gilead: Honoraria; MSD: Honoraria; Novartis: Honoraria; Neovii: Research Funding. Deau Fischer:Takeda: Consultancy; Roche: Consultancy.

Background Peripheral T-cell lymphoma (PTCL) is a heterogeneous and accounts for approximately 10% of all lymphomas. Outcome of relapse/refractory (R/R) PTCL is poor with median progression-free survival (PFS) and overall survival (OS) of 3 and 6 months in the absence of stem-cell transplantation (SCT). [Mak, JCO, 2013]. Brentuximab vedotin (BV) monotherapy is approved for R/R systemic anaplastic large cell-lymphoma (ALCL) based on 86% overall response rate (ORR) and 57% complete remission (CR). [Pro, JCO, 2012]. In other CD30-positive (CD30+) R/R PTCL, the ORR of BV is 41%. Gemcitabine (G) used as monotherapy in control arm in the randomized phase 3 LUMIERE trial, provided ORR and CR rates of 35 and 22% respectively. [O'Connor, JCO, 2019]. Considering these results we designed a phase 2 study for R/R CD30+ PTCL combining G and BV with the primary end point to increase the ORR by 15%, compared to G monotherapy. Patients (pts) and Methods: Pts with histologically confirmed CD30+ (≥5%) PTCL who failed or were refractory to 1-3 prior lines of systemic therapy, with measurable disease and ECOG performance status < 3 were eligible. Pts received an induction of 4 cycles of G-BV (28-days cycles; G: 1000 mg/m² at D1 and D15 plus BV: 1.8 mg/kg at D8). Pts with CR or partial remission (PR) and non-eligible for SCT, received BV maintenance 1.8 mg/kg at D1 (21-days cycles) up to 12 cycles. The primary endpoint was the ORR (CR + PR) according to Lugano criteria based on CT-scan. Secondary objectives included tolerance and safety, DOR, PFS, OS and impact of BV maintenance. Eligible pts were censored at time of SCT. (NCT03496779). Results: From April 2018 to October 2019, 71 pts were included. Pathology central review according to WHO 2017 criteria, so far available for 50 patients, confirmed angioimmunoblastic T-cell lymphoma (AITL) (22 ; 31%); nodal PTCL-TFH (5 ; 7%); PTCL-NOS (5 ; 7%); ALK- ALCL (10 ; 14.1%) ; ALK+ ALCL (4 ; 5.6%), Enteropathy associated T-cell lymphoma (EATL) (2 ; 2.8%); unclassified PTCL (2 ; 2.8%). There were 47 male and 24 female with a median age of 66 years (20-79) and 17 pts were > 75 years. Median time from diagnosis to enrolment was 9.4 months (range, 6-21). Sixty-five pts (91.6%) presented with stage III-IV. The number of prior lines of therapy were 1 (57 pts), 2 (11 pts) or 3 (3 pts), all pts had received previous CHOP-like chemotherapy, 11 pts previous autologous SCT, 5 pts epigenetic modifiers and 39.4% were refractory to their last line of treatment prior to inclusion. The cut-off date of this analysis was 01/31/2020. The 4 cycles of G-BV induction were completed in 45 pts (63%). The reasons for early discontinuation were progression (21 pts), death (3 pts) or adverse event (2 pts). In intention-to-treat analysis, the ORR at the end of induction (EOI) was 47.9% including CR (14 pts; 19.7%), PR (20 pts; 28.2%). PET performed in all patients reaching EOI showed overall and complete metabolic responses in 45.1 and 23.9%, respectively. During G-BV induction 58 pts (81.7%) had at least one G > 3 adverse event (AE) including neutropenia (67.2%), thrombopenia (17.2%), infections (15.5%), peripheral neuropathy (PN) (5.2%) and cardiac event (5.2%). Overall PN of any grade was recorded in 8/71 patients (11%) during G-BV induction and caused BV withdrawal in one case. Among the 34 responding pts after EOI, 27 pts began BV maintenance and 7 pts remain on maintenance at cut-off date. Eight pts were removed from the study due to SCT eligibility, either after the 4 GBV induction (4 pts) or after 1 or 2 maintenance BV cycles (4 pts). With a median follow-up (FU) of 9.5 (0.5-19.4) months, median PFS is 4.5 months (95%CI [3.5 - 10]) and median OS is 12 months (95%CI [8.6 - NR]). Among the 34 patients in PR/CR after induction, the duration of response (DOR) is 12.8 months (95%CI [10.3 - NR]). At last FU were recorded 32 deaths. Disease status at time of death was PD (25 pts), CR (1 pt) NE or missing (6 pts). Conclusion: The addition of BV to G increases the overall response rate by 15% in the treatment of R/R CD30+ PTCL. OS data are encouraging for this overall R/R patient population but PFS is overall short and a longer FU is mandatory. Especially the DOR of pts achieving CR or PR after 4 cycles of G-BV exceeds 1 year on BV maintenance. This combination is generally well tolerated and this study suggests that G-BV combination could be an interesting alternative for R/R CD30+ PTCL. Disclosures Tournilhac: Janssen: Consultancy, Honoraria, Other: Travel grant; INNATE Pharma: Consultancy, Honoraria; GILEAD: Consultancy, Honoraria, Other: Travel Grant; ABBVIE: Consultancy, Honoraria, Other: Travle grant; Takeda: Consultancy, Honoraria, Other: Travel grant. Laribi:novartis: Honoraria, Research Funding; amgen: Research Funding; abbvie: Honoraria, Research Funding; takeda: Research Funding. Ysebaert:AbbVie: Consultancy; Roche: Consultancy; Janssen: Consultancy. Guidez:BMS: Honoraria; TAKEDA: Honoraria; Service Hématologie et Thérapie cellulaire CHU POITIERS: Current Employment; AMGEN: Honoraria; CELGENE: Honoraria; JANSEN: Honoraria. Le Gouill:Loxo Oncology at Lilly: Consultancy; Roche Genentech, Janssen-Cilag and Abbvie, Celgene, Jazz pharmaceutical, Gilead-kite, Loxo, Daiichi-Sankyo and Servier: Honoraria. André:Celgene: Other, Research Funding; Takeda: Consultancy; Bristol-Myers-Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Karyopharm: Consultancy; Gilead: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Consultancy, Research Funding; Amgen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Johnson & Johnson: Research Funding; CHU UCL Namur, site Godinne, Yvoir, Belgium: Current Employment; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Abbvie: Consultancy; Seattle Genetics: Consultancy. Dupuis:Henri Mondor University Hospital Creteil France: Current Employment. Thieblemont:Roche, Amgen, Kyte Gilead, Celgene, Abbvie, Novartis, Cellectis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Roche, Hospita: Research Funding; Cellectis: Speakers Bureau. Bachy:Beigene: Membership on an entity's Board of Directors or advisory committees; Roche, Gilead: Consultancy; Amgen: Research Funding; Roche, Celgene, Amgen, Janssen, Gilead, Novartis, Sanofi: Honoraria. Morschhauser:Celgene: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; F. Hoffmann-La Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Epizyme: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Servier: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Feugier:janssen: Consultancy, Honoraria, Research Funding; gilead: Consultancy, Honoraria, Research Funding; roche: Consultancy, Honoraria, Research Funding; astrazeneca: Consultancy, Honoraria, Research Funding; abbvie: Consultancy, Honoraria, Research Funding. Cartron:F. Hoffmann-La Roche: Consultancy, Honoraria; Abbvie: Honoraria; Jansen: Honoraria; Celgene: Consultancy, Honoraria; Sanofi: Honoraria; Gilead: Honoraria. Camus:ROCHE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); JANSSEN: Honoraria; AMGEN: Honoraria; PFIZER: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Sibon:takeda france: Consultancy. Snauwaert:roche: Other: travel; janssen: Other: travel; abbvie: Other. Delarue:BMS: Other: stock options ; Celgene/BMS: Current Employment. De Leval:Abbvie: Honoraria; Lausanne University Hospital & Lausanne University Institute of Pathology: Current Employment; Roche Diagnostics: Honoraria; Lunaphore Technologies SA: Consultancy, Honoraria. Gaulard:CHU Henri Mondor, Assistance Publique-Hôpitaux de Paris: Current Employment; TAKEDA: Consultancy, Honoraria, Research Funding; INNATE PHARMA: Research Funding; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company).

Long-term efficacy of anti-PD1 therapy and the need for a consolidation with allogenic haematopoietic stem cell transplantation (allo-HSCT) remain unclear in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL).We retrospectively analysed 78 patients with R/R HL treated with nivolumab in the French Early Access Program and compared their outcomes according to subsequent allo-HSCT.After a median follow-up of 34.3 months, the best overall response rate was 65.8%, including 38.2% complete responses (CRs). The median progression-free survival (PFS) was 12.1 months. Patients reaching a CR upon nivolumab had a significantly longer PFS than those reaching a partial response (PR) (median = not reached vs 9.3 months, p 0.001). In our cohort, 13 patients who responded (i.e. in CR or PR) to nivolumab monotherapy underwent consolidation with allo-HSCT. Among responding patients, none of those who underwent subsequent allo-HSCT (N = 13) relapsed, whereas 62.2% of those who were not consolidated with allo-HSCT (N = 37) relapsed (p 0.001). There was no difference in overall survival (OS) between the two groups. Five of 6 patients who were not in CR at the time of transplantation (4 PRs and 1 progressive disease) converted into a CR after allo-HSCT.Most patients with R/R HL treated with anti-PD1 monotherapy eventually progressed, notably those who did not achieve a CR. Patients undergoing consolidation with allo-HSCT after anti-PD1 therapy experienced prolonged disease-free survival compared with non-transplanted patients, but this difference did not translate into a benefit in OS. This information should be considered when evaluating the risk/benefit ratio of allo-HSCT after anti-PD1 therapy.

High-dose chemotherapy before autologous transplantation is a therapeutic option as consolidation in primary or relapsed lymphoma. Even if BEAM conditioning is generally used, alternative conditioning regimens have been published. The purpose of this study was to assess the outcome of 177 adult patients with lymphoma whose conditioning treatment included a BAM (busulfan, aracytine, and melphalan) regimen. With a median follow-up of 17.4 months, 2-year estimates of overall survival and progression-free survival for the entire group were 87% and 70.5%, respectively. Mucositis was the main reported complications and infectious episodes were described in 80.2% of patients. According to multivariate analysis, high performance status and age at diagnosis were adverse factors for survival and increased the risk of disease relapse and death. Despite its limitations, this retrospective study suggests that BAM combination is a valid conditioning regimen in lymphoma patients, with an acceptable rate of toxicity.

ObjectiveReal-life studies on patients with primary CNS lymphoma (PCNSL) are scarce. Our objective was to analyze, in a nationwide population-based study, the current medical practice in the management of PCNSL.MethodsThe French oculo-cerebral lymphoma network (LOC) database prospectively records all newly diagnosed PCNSL cases from 32 French centers. Data of patients diagnosed between 2011 and 2016 were retrospectively analyzed.ResultsWe identified 1,002 immunocompetent patients (43% aged >70 years, median Karnofsky Performance Status [KPS] 60). First-line treatment was high-dose methotrexate-based chemotherapy in 92% of cases, with an increasing use of rituximab over time (66%). Patients 60 years of age, WBRT and HCT-ASCT consolidation were administered in only 9% and 2%, respectively. The complete response rate to initial chemotherapy was 50%. Median progression-free survival was 10.5 months. For relapse, second-line chemotherapy, HCT-ASCT, WBRT, and palliative care were offered to 55%, 17%, 10%, and 18% of patients, respectively. The median, 2-year, and 5-year overall survival was 25.3 months, 51%, and 38%, respectively (60 years: 15.4 months, 44%, and 28%). Age, KPS, sex, and response to induction CT were independent prognostic factors in multivariate analysis.ConclusionsOur study confirms the increasing proportion of elderly within the PCNSL population and shows comparable outcome in this population-based study with those reported by clinical trials, reflecting a notable application of recent PCNSL advances in treatment.

Introduction Treatment of B-lineage lymphoma with B-cell depleting immunotherapy causes B-cell aplasia and impairs immune response. Case studies have reported patients treated with anti-CD20 therapy who suffered from persistent Covid-19. We aimed to assess the incidence, risk factors and long-term outcomes of persistent Covid-19 in patients with lymphoma. Patients and methods This retrospective multicentric study was conducted in 16 French hospitals. All adult patients with lymphoma who were admitted for Covid-19 in March and April 2020 were included. Persistent Covid-19 was defined as persisting severe Covid-19 symptoms requiring in-hospital stay for >30 days. Patients who re-experienced severe Covid-19 symptoms after initial improvement, requiring repeated hospitalizations for a total in-hospital length of stay >30 days were added to the persistent Covid-19 cases. Results One hundred eleven patients were included. Thirty days after admission for Covid-19, 24 patients had died, 55 had been definitively discharged from hospital, 31 were still hospitalized and 1 was later rehospitalized for Covid-19 recurrence. The incidence of persistent Covid-19 was 32/111 (29%). Patients with persistent Covid-19 had a median age of 64 years (range, 43-87) and 63% were male. Twenty-two patients (69%) had at least one significant comorbidity. None of the patients with T-cell (n=8) lymphoma or classical Hodgkin’s disease (n=8) experienced persistent Covid-19. In the 32 patients with persistent Covid-19, the median time between first admission and final discharge was 58 days (range, 31-235) and the median duration of Covid-19 symptoms was 83 days (range, 32-237). Eight patients received corticosteroids and 9 convalescent plasma: all patients recovered from their symptoms, except one. Overall, 9 patients with persistent Covid-19 died (27%). After a median follow-up of 191 days (range, 3-260), the 6-month overall survival was 69% (95% CI 60-78%) for the whole cohort. In multivariate analysis, administration of anti-CD20 monoclonal antibody within 12 months before admission to hospital for Covid-19 was both associated with decreased overall survival (HR 2.13, 95% CI 1.03-4.44, p = 0.043) and prolonged in-hospital stay (HR 1.97, 95% CI 1.24-3.13, p = 0.004). The two other significant factors associated with decreased overall survival and prolonged in-hospital stay: age ≥ 70 years and refractory or relapsed lymphoma. Conclusion Patients with B-cell non-Hodgkin lymphoma hospitalized for Covid-19 have a high incidence of prolonged evolution of SARS-CoV-2 infection. Administration of anti-CD20 therapy within the last 12 months is one of the main risk factors for longer in-hospital stay and death of Covid-19. The risk of persistent Covid-19 was also higher in patients older than 70 years or with refractory or relapsed disease. These findings may contribute to guide the management of lymphoma patients during the Covid-19 pandemic. Citation Format: Sylvain Lamure, Remy Dulery, Marc Delord, Roberta Di Blasi, Adrien Chauchet, Thomas Hueso, Cédric Rossi, Bernard Drenou, Bénédicte Deau-Fischer, Carole Soussain, Pierre Feugier, Nicolas Noel, Sylvain Choquet, Serge Bologna, Bertrand Joly, Laure Philippe, Milena Kohn, Sandra Malak, Guillemette Fouquet, Etienne Daguindau, Sophie Bernard, Yassine Taoufik, Karine Lacombe, Guillaume Cartron, Catherine Thieblemont. High incidence of persistent COVID-19 among patients with lymphoma treated with B-cell depleting immunotherapy [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr S09-02.

Introduction: Older patients with an age above 60 years with classical Hodgkin lymphoma (cHL) represent a proportion of 20% to 30% of all cHL. Older cHL patients are characterized by unfavorable prognostic factors with an aggressive disease, a poor tolerance to chemotherapy especially with bleomycin-induced lung toxicity resulting to a significant reduced survival as compared to younger patients. PVAG regimen (prednisone, vinblastine, doxorubicin, gemcitabine) was developed by the German Hodgkin Study Group (GHSG) to improve results and reduce toxicities of ABVD regimen. In a prospective phase II study of 55 early unfavorable and advanced-stage elderly HL patients (median age, 68 years), 78% achieved complete response (CR) with a 3-year progression free survival (PFS) and overall survival (OS) rates of 58% and 66%, respectively (Böll et al, Blood 2011) with favorable toxicity profile. To the best of our knowledge, there is no report that described efficacy and toxicity of this protocol in real-life setting. Methods: Between June 2011 and February 2020, 49 elderly patients with cHL received first-line chemotherapy with PVAG (Prednisone 40 mg/m2, Vinblastine 6 mg/m2, Doxorubicin 50 mg/m2, Gemcitabine 1000 mg/m2, or adapted-dose of PVAG) in 6 LYSA centers. All medical records were reviewed for clinical and biological characteristics, modality of treatment, responses and outcome. Comorbidities were evaluated according to the cumulative illness rating scale for geriatrics (CIRS-G) and treatment-related toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). Results: The median age of the 49 patients was 76 years (range, 61-87) with 44 patients ≥70 years old (69%) and 27 male (55%). Ann Arbor stages were as follows: II (n=16, 33%), III (n=12, 24%), IV (n=21, 43%). Altered performance status (PS 2-4) was presented in 35% of patients and B symptoms in 59%. IPS was ≥3 in 32 (65%) patients. CIRS-G Grade 3 or 4 in two or more categories was observed in 11 patients (22%) and 22 patients (43%) had a cumulative CIRS-G score over 6. Patients received a median of 6 cycles (range 1-8), 21 of them (43%) received adapted dose of PVAG. Seven patients (14%) received radiotherapy after respectively 3, 4, 6, or 8 cycles of PVAG. At the end of PVAG regimen, 26 patients were in CR (53%), 4 PR (8%), 19 patients progressed (39%). For the 46 patients who were evaluated by PET-CT after chemotherapy, the CR and PR rates were 52% and 13% with 35% of patients with stable or progressive diseases. For hematologic toxicity, 6 patients (12%) developed febrile neutropenia, 22 (45 %) had grade III-IV neutropenia; 8 (16 %) a grade 3-4 thrombopenia; 17 (35%) grade 3-4 anemia. Extra-hematologic toxicities were mild with three patients (6%) with grade 3-4 mucositis, 2 (4%) grade 3-4 nausea, 5 (10%) with grade 3-4 neuropathy, 3 (6%) acute heart toxicity. With a median follow up of 33,2 months (range, 14,3 -53,7), 26 (53%) patients progressed or relapsed. The median PFS was 21,6 months with a 3-year PFS rate of 48,6% (95%CI, 36,3-65,1). The median overall survival (OS) was 66,5 months with a 3-year OS rate of 73,7% (95%CI, 61,2-88,8). The cause of death was HL in 8 patients (16%), infection in 2 (4%); one toxic death occurred (sepsis after first cycle of PVAG). In univariate analysis, PFS (HR: 2,36, 95CI, 1,01-5,48, P=0.0,046) and OS (HR: 4,23, 95%CI, 1,15-15,6, P=0.03) were adversely affected by high number of medications (>3). OS was adversely affected by grade 3-4 CIRS-G in ≥2 categories (HR: 3,63, 95%CI, 1,23-10,71, P=0.019). Age, IPS, presence of B symptoms, lymphopenia, anemia, low albumin level, CIRS-G>6 did not affect outcome. Conclusions:Our real-life evaluation of PVAG regimen showed that patients were older than those included in the pivotal clinical trial and 58% of patients received adapted-dose of chemotherapy. We confirmed the favorable safety profile of this protocol. Using TEP-scan evaluation, the CR rate was 52%. Survival analyses supported initial results obtained in clinical trial. Combinations with immunotherapies with clinical activity in cHL should be evaluated to improve results of this regimen. Disclosures Brice: Takeda: Consultancy; Roche: Consultancy. Salles:Epizyme: Honoraria, Other: consultancy or advisory role; Kite, a Gilead Company: Honoraria, Other: consultancy or advisory role ; Janssen: Honoraria, Other: consultancy or advisory role; BMS/Celgene: Honoraria, Other: consultancy or advisory role; Takeda: Honoraria; Karyopharm: Honoraria; Genmab: Honoraria, Other; Debiopharm: Consultancy, Honoraria, Other: consultancy or advisory role; MorphoSys: Honoraria, Other: consultancy or advisory role; Novartis: Honoraria, Other: consultancy or advisory role; Roche: Honoraria, Other: consultancy or advisory role; Abbvie: Other: consultancy or advisory role; Autolos: Other: consultancy or advisory role. Deau Fischer:Takeda: Consultancy; Roche: Consultancy.

Background: Nivolumab demonstrated remarkable activity in patients with relapse or refractory (R/R) Hodgkin lymphoma (HL). However, long term efficacy and the need for a consolidation with allogenic stem cell transplantation remain unclear. Patient and method: We retrospectively analyzed 78 patients with R/R HL treated with nivolumab in the French Early Access Program and compared their outcome according to subsequent alloHSCT. Results: After a median follow-up of 31.5 months, the best overall response rate was 64%, including 37.3% complete response (CR). The median progression-free survival (PFS) was 12.1 months and median overall survival (OS) was not reached. At 3 years, PFS and OS rates were 35% and 65%, respectively. Patients reaching a CR upon nivolumab had a significantly longer PFS than those reaching a PR (median = not reached vs 10.1 months). In our cohort, 17 patients underwent consolidation with allogenic stem cells transplantation (alloHSCT) after nivolumab therapy (Figure 1). At the time of transplantation, 8 patients were in CR, 5 in partial response (PR) and 4 had progressed of whom 3 received a salvage therapy before alloHSCT. Interestingly, 6 out of 7 patients who were not in CR at the time of transplantation (5 PR and 1 progressive disease) converted into a CR after alloHSCT. At the time of analysis, 14 patients were alive and 13 remained disease-free after a median follow-up of 30.4 months. One-year OS and PFS from alloHSCT were 82% and 76%, respectively. Among responding patients (i.e. in CR or PR) after nivolumab monotherapy, those who underwent subsequent alloHSCT (N=13) had a better outcome than those who were not consolidated with alloHSCT (N=35) (Figure 2). In the transplanted group, none of the patients relapsed whereas in the non-transplanted group 60% of the patients relapsed (p Conclusions: Although patients who achieve a CR upon anti-PD1 therapy may experience prolonged remissions, most R/R HL patients treated with anti-PD1 antibody eventually progress or relapse. Our study demonstrates unprecedented disease-free survival in patients undergoing consolidation with alloHSCT after anti-PD1 therapy. Interestingly, alloHSCT post anti-PD1 can convert incomplete responses into CR in most cases. Despite expected toxicities, alloHSCT after anti-PD1 therapy appears manageable and safe in most patients. Our results suggest that consolidation with alloHSCT may represent a good option in patients treated with anti-PD1, notably in patients who are unable to achieve a CR. Disclosures Herbaux: Gilead Sciences, Inc.: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Stamatoullas:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA: Consultancy. Brice:bristol myers squibb: Consultancy, Honoraria. Houot:bristol myers squibb: Consultancy, Honoraria.

ObjectiveTo investigate patterns of care during the last months of life of hospitalised patients who died from different haematological malignancies.MethodsNationwide register-based study, including all hospitalised adults ≥20 years who died from haematological malignancies in France in 2010–2013. Outcomes included use of invasive cancer treatments and referral to palliative care. Percentages are adjusted for sex and age using direct standardisation.ResultsOf 46 629 inpatients who died with haematological malignancies, 24.5% received chemotherapy during the last month before death, 48.5% received blood transfusion, 12.3% were under invasive ventilation and 18.1% died in intensive care units. We found important variations between haematological malignancies. The use of chemotherapy during the last month of life varied from 8.6% among patients with chronic myeloid leukaemia up to 30.1% among those with non-Hodgkin’s lymphoma (PConclusionA high proportion of patients who died from haematological malignancies receive specific treatments near the end of life. There is a need for a better and earlier integration of the palliative care approach in the standard practice of haematology. However, substantial variation according to the type of haematological malignancy suggests that the patients should not be considered as one homogeneous group. Implementation of palliative care should account for differences across haematological malignancies.

IF 5.303; International audience; 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, twelve obtained PR or complete response (CR). In Group 1, there were 7 CR (41%), 3 PR (18%), and 7 PD (41%). In Group 2, there were 4 CR (57%), 2 PR (29%), and 1 SD (14%). No unexpected toxicity was observed. Six patients who achieved response proceeded to allogeneic SCT. With a median follow-up of 12.1 months (7-14.7), the median PFS following the initiation of CT was 11 months (95%CI, 6.3; not reached) and the median of overall survival was not reached. These observations in highly pre-treated HL patients suggest that anti-PD-1 therapy might re-sensitize tumor cells to CT. This article is protected by copyright. All rights reserved.

International audience; Mucormycosis is an invasive mold infection, frequently fatal in immunocompromised patients. We report the case of a patient with chronic lymphocytic leukemia admitted to the hematology unit for febrile aplasia. Pulmonary lesions suggesting a fungal infection expanded/increased despite a combination of posaconazole and liposomal amphotericin B. The fungal biomarkers performed repeatedly were negative. At D65 after chemotherapy a bronchial biopsy was positive for Cunninghamella bertholletiae. The patient died despite appropriate antifungal management. A qPCR targeting Cunninghamella was developed a posteriori, and a retrospective analysis showed that a sample was positive more than 30 days before culture-based identification could be made.

Background Peripheral T-cell lymphoma (PTCL) remains a therapeutic challenge. Due to the rarity and the heterogeneity of PTCL, no consensus has been achieved regarding even the type of first-line treatment. The benefit of autologous stem-cell transplantation (ASCT) is, therefore, still intensely debated. Patients and methods In the absence of randomized trials addressing the role of ASCT, we performed a large multicentric retrospective study and used both a multivariate proportional hazard model and a propensity score matching approach to correct for sample selection bias between patients allocated or not to ASCT in intention-to-treat (ITT). Results Among 527 patients screened from 14 centers in France, Belgium and Portugal, a final cohort of 269 patients ≤65 years old with PTCL-not otherwise specified (NOS) (N = 78, 29%), angioimmunoblastic T-cell lymphoma (AITL) (N = 123, 46%) and anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-ALCL) (N = 68, 25%) with partial (N = 52, 19%) or complete responses (N = 217, 81%) after induction was identified and information about treatment allocation was carefully collected before therapy initiation from medical records. One hundred and thirty-four patients were allocated to ASCT in ITT and 135 were not. Neither the Cox multivariate model (HR = 1.02; 95% CI: 0.69–1.50 for PFS and HR = 1.08; 95% CI: 0.68–1.69 for OS) nor the propensity score analysis after stringent matching for potential confounding factors (logrank P = 0.90 and 0.66 for PFS and OS, respectively) found a survival advantage in favor of ASCT as a consolidation procedure for patients in response after induction. Subgroup analyses did not reveal any further difference for patients according to response status, stage disease or risk category. Conclusions The present data do not support the use of ASCT for up-front consolidation for all patients with PTCL-NOS, AITL, or ALK-ALCL with partial or complete response after induction.

Purpose Follicular lymphoma (FL) accounting for 20% of non-Hodgkin lymphoma, is currently considered treatable but not curable despite more effective treatment options. Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase δ (PI3Kδ) that blocks PI3Kδ-AKT signaling and promotes apoptosis, is approved for patients with relapsed/refractory (R/R) FL who have received ≥ 2 prior systemic therapies. Previous studies suggest that somatic tumor mutations identified at relapse may have an impact on the response to targeted therapies (Bartlett N et al., Blood 2018). The goal of this study was to analyze the lymphoma mutational profile to identify the prognostic value of mutations in R/R follicular lymphoma patients treated with idelalisib. Methods We performed a retrospective multicenter study of patients (pts) with relapsed follicular lymphoma and no evidence of transformation, having received at least 2 prior regimens before idelalisib treatment. Patients received idelalisib 150mg BID until progression or toxicity. Next-generation sequencing (NGS) of 51 genes was performed either at FL diagnosis and/or at relapse prior idelalisib therapy. The primary endpoint was to analyze the relationship between the mutational status and the duration of response (DOR) to idelalisib. DOR was measured from the time of initial response until documented lymphoma progression. According to DOR pts were classified as: refractory (response < 1 month), short-responder (1 month ≤ DOR ≤ 12 months) and long-responder (> 12 months). Results 24 pts with R/R FL were enrolled with a median age of 62.5 years (range: 57-86). Patients had received a median of 3 prior treatments (range: 2-7). FL was refractory to rituximab in 16 pts (67%), to alkylating agents in 11 pts (46%) and to 2 or more prior treatments in 11 pts (46%). Twelve (50%) had refractory disease to the last therapy before idelalisib. Pts received idelalisib during a median of 5.5 months (range: 0.5-31). Overall response rate was 83% (n=20) including 3 (15%) complete response and 17 (85%) partial response. The median DOR was 9.5 months (range: 0-28). Eleven pts were short-responders and 9 long-responders. Four pts (17%) had refractory disease to idelalisib. Median progression-free survival and overall survival were 11.5 (range: 1-30) and 16.5 months (range: 1-56) respectively. Three pts (12.5%) are still continuing idelalisib. Twenty-one pts (87.5%) discontinued treatment mostly due to progressive disease (n=14) and adverse events (n=5); 3 pts remained progression-free after idelalisib discontinuation and observation with a median follow-up of 23 months (range: 20-24). All the pts had at least one mutation detectable for one of the targeted genes in both diagnosis (n=17) and relapse (n=20) samples. The median number of targeted genes with non-silent mutations per patient was 7 at diagnosis (range: 2-11) and 6 at relapse (range: 3-28). The most frequent genes found in 10% of patients (≥ 2) or more at diagnosis and at relapse are listed in Figure 1. The mutational profile at diagnosis predominantly included mutations in epigenetics gene family, KTM2D (n=16; 94%), EP300 (n=9; 52%), ARID1A (n=6; 35%), KTM2A (n=5; 29%) and CREBBP (n=4; 23%). The m7-FLIPI score (Pastore A et al., Lancet Oncology 2015) at diagnosis helped identifying pts with low-risk (n=12; 71%) and high-risk (n=5; 29%) of idelalisib treatment failure. The median m7-FLIPI score in the refractory group was 1.25 compared to 0.26 in the short responder group and 0.04 in the long responder group. All long responder patients had low-risk m7-FLIPI. The mutational profile at relapse was significantly enriched in mutations of TNFAIP3 (n=7; 35%) and NFKBIE (n=4; 20%), affecting the NF-kB inhibitor pathway, and mutations of transcription factors, TP53 (n=10; 50%), MEF2B (n=5; 25%), FOXO1, STAT6 and IRF4 (n=4; 20% each). Overall the mutational profile of the 3 sub-groups according to DOR was detailed in Figure 2. The genes more frequently mutated in refractory pts were: EP300 (n=3/4; 75%), B2M (n=2/4; 50%), FBXW7 (n=2/4; 50%), CARD11, CXCR4 and MYD88 (n=1/4; 25% each). Conclusion The m7FLIPI at diagnosis identifies patients with higher risk of treatment failure in patients with R/R FL treated with idelalisib. Patients with idelalisib refractory disease have more frequently mutations of EP300, B2M, FBXW7, which suggests they could be related to resistance to idelalisib. Disclosures No relevant conflicts of interest to declare.

Allogeneic hematopoietic cell transplantation (allo-HCT) is indicated for patients with relapsed or refractory Hodgkin lymphoma (HL). Although long-term disease control can be achieved, relapse is still frequent. The programmed cell death protein 1 (PD-1) pathway-blocking antibody nivolumab has shown substantial therapeutic activity and an acceptable safety profile in patients with relapsed or refractory HL who did not receive allo-HCT. However, PD-1 blocking strategy can increase the risk of graft-versus-host disease (GVHD) in murine models. We retrospectively assessed the efficacy and toxicity of nivolumab as a single agent in 20 HL patients relapsing after allo-HCT. GVHD occurred in 6 patients (30%) after nivolumab initiation. All 6 patients had prior history of acute GVHD. The patients with nivolumab-induced GVHD were managed by standard treatment for acute GVHD. Two patients died as a result of GVHD, 1 of progressive disease and 1 of complications related to a second allo-HCT. Overall response rate was 95%. At a median follow-up of 370 days, the 1-year progression-free survival rate was 58.2% (95% CI, 33.1%-76.7%) and the overall survival rate was 78.7% (95% CI, 52.4%-91.5%). Among 13 patients still in response, 6 received a single dose of nivolumab and 7 remain on nivolumab. Compared with standard options for this indication, our results show that nivolumab is effective with an acceptable safety profile.

Introduction: Hodgkin lymphoma (HL) pts who relapse after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV) therapy have a poor outcome. For these relapsed and refractory (R/R) HL pts, anti-PD-1 therapy gives a high rate of objective responses. However, the rate of complete response (CR) remains modest and in the updated results of anti-PD-1 therapy clinical trials, about 50% of pts are still without progressive disease after one year of treatment. As anti-PD-1 therapy modifies the anticancer immune response, we hypothesize that anti-PD-1 therapy may increase sensitivity to chemotherapy (CT) given after anti-PD-1 therapy (sequential strategy) or in combination with anti-PD-1 therapy after an unsatisfactory response to immunotherapy (concomitant strategy). We retrospectively analyzed these two clinical situations in 30 R/R HL pts from LYSA centers treated with anti-PD-1 therapy. Methods: We included R/R HL pts from 14 LYSA centers who received anti-PD-1 therapy in the context of clinical trials (N=4) or an authorization for temporary use (ATU) from the French medical drug agency (N=26). Before the anti-PD-1 therapy, pts had received a median of six (range, 2-14) lines of therapy, 69% had HDT+ASCT, 14% had allograft and 93% had been treated with BV. We considered two groups of pts: i. 19 pts (63%) in whom the anti-PD-1 therapy was stopped at the introduction of CT (Group 1); ii. 11 pts (37%) with an unsatisfactory response to anti-PD-1 therapy in whom a combination of CT with immunotherapy was initiated to optimize the response (Group 2). The quality of the response after the introduction of CT was evaluated retrospectively by each treating physicians according to Cheson 2007 or 2014 criteria. We also determined whether new CT treatments after and in combination with anti-PD-1 therapy led to unexpected toxicities and whether new treatment schedules made pts eligible for allograft. Results: At the start of anti-PD-1, the median age of pts was 37 years old (range, 20-75), 24% had Ann Arbor III/IV stages, 34% had B symptoms and 21% had a performance status (PS) of 2-3. Patients received a median of 10 infusions (range, 2-52) of anti-PD-1 therapy with nivolumab (N=26, 87%) or pembrolizumab (N=4, 13%). The best responses achieved during anti-PD-1 therapy were a complete response (CR) for 5 patients, a partial response (PR) for 17 pts, stable disease (SD) for 2 pts and progression for 6 pts. In group 1, 17 pts were in progression, one pt in PR, and another pt in SD at the end of anti-PD-1 therapy alone. In group 1, after anti-PD-1 therapy, the pts were treated with vinblastine (N=3), gemcitabine (N=2) or bendamustine alone (N=3) or in combination with BV (N=4), GVD (N=1), ICE (N=1), DHAP (N=1), escalated BEACOPP (N=1), vinorelbine (N=1), vepeside (N=1) and caelyx (N=1). In group 2, before the combination, the response status was progression for 7 pts and PR for 4 pts. In group 2, to optimize the response to anti-PD-1, pts received vinblastine (N=7), gemcitabine (N=2) and BV (N=2). In the 28 evaluable pts, 11/18 (61%) in group 1 and 9/10 (90%) in group 2 showed an improved response after chemotherapy alone or combination with anti-PD-1 therapy respectively. In group 1, there were 6 CR (32%), 5 PR (26%), 1 SD (5%) and 6 PD (32%) (Figure 1B). In group 2, there were 5 CR (45%), 5 PR (45%) and 1 SD (10%) (Figure 1A). Of note, among the ten pts treated with vinblastine, 4 were in CR, 3 in RP, 1 in SD and 2 in progression. No unexpected toxicity was observed during the CT. Four pts had an allograft after the sequential CT (N=3) and concomitant CT strategy (N=1). Three pts were in CR 274, 279 and 480 days after the allograft and the fourth has not yet been evaluated. Allografts are now scheduled for 6 pts. With a median follow-up of 9.1 months (95%CI, 6.1-14) following the initiation of chemotherapy (alone or combined) the median PFS and OS were 8.4 and 14.6 months, respectively. Conclusions: Our retrospective study showed that pts with an unsatisfactory response or PD with anti-PD-1 therapy had a new objective response with CT alone (61%) or CT in combination with anti-PD-1 therapy (90%). This response could make some pts eligible for allograft. Prospective clinical trials are needed to confirm the synergistic effect of CT with anti-PD-1 therapy and to determine which CT provides the best results in combination with these checkpoint inhibitors. Figure 1 Figure 1. Disclosures Ysebaert: Janssen: Consultancy, Research Funding, Speakers Bureau. Ghesquières: Celgene and Mundipharma: Consultancy, Honoraria; Roche: Research Funding.

International audience; BACKGROUND: An increased incidence of alveolar echinococcosis (AE) in patients with immunosuppression (IS) has been observed; our aim was to study this association and its characteristics. METHODS: Fifty AE cases with IS-associated conditions (ISCs) before or at AE diagnosis were collected from the French AE registry (1982-2012, 509 cases). There were 30 cancers, 9 malignant hematological disorders, 14 chronic inflammatory diseases, 5 transplants, and 1 case of AIDS; 9 patients had ≥2 ISCs. Characteristics of the 42 IS/AE cases and the 187 non-IS/AE cases diagnosed during the period 2002-2012 were statistically compared. RESULTS: There was a significant increase in IS/AE cases over time. Risk factors did not differ between IS/AE and non-IS/AE patients. However, AE was more frequently an incidental finding (78% vs 42%) and was diagnosed at earlier stages (41% vs 23%) in IS/AE than in non-IS/AE patients. Serology was more often negative (14% vs 1%) and treatment efficacy was better (51% regression after 1-year treatment vs 27%) in IS/AE patients. All IS/AE patients but 7 took IS drugs; 7 received biotherapeutic agents. When not concomitant, AE occurred in IS patients within a 48-month median time period. Atypical presentation and abscess-, hemangioma-, and metastasis-like images delayed AE diagnosis in 50% of IS/AE patients, resulting in inappropriate treatment. Liver images obtained for 15 patients 1-5 years before diagnosis showed no AE lesions. Albendazole efficacy was good, but 19 of 48 treated patients experienced side effects. CONCLUSIONS: Patients with immunosuppression are at increased risk for occurrence, delayed diagnosis, and progression of AE.

Unavailability of Carmustine and its dramatically increased cost by nearly 10 fold has led to its replacement by bendamustine (Be) and an increase use of Bendamustine-based (BeEAM) conditioning regimen before autologous stem cell transplantation for lymphoma. The aim of this study was to evaluate the safety of the BeEAM regimen in the real life use in several French centers. Median age of the 386 patients (233 male, 153 female) was 55 years (17-72). The majority of patients had aggressive B-cell (40%), follicular (17%), Hodgkin's (17%) and mantle cell lymphoma (15%). Two hundred and forty six patients (64%) were transplanted after 2nd line chemotherapy and the median number of prior lines of chemotherapy of 2 (1-9). Two hundred and sixty patients (67%) had received prior platinum chemotherapy and only 4% had a history of prior chronic renal failure (Table 1). The median creatinine level at conditioning initiation was 71(36-206) µmol/l. Be was administered at a median dose of 191 mg/m2/day (50-250) on day -7 and -6. Thirty two percent received 100-160 mg/m²/d and 58% of patients received more than 160 mg/m²/d. Median 24h-hydration volume was 3 l (1-6) which began within median time of 18 h (1-72) prior to conditioning initiation. The median duration time of Be perfusion was 60 min (30-143). Grade 1-4 acute renal failure (ARF) was reported in 107 cases (28%) (G ≥2; 34%) and appeared after a median time of 2 days (1-18) after conditioning start. Melphalan dosage was reduced, due to renal failure, in 10% of patients (Table 2). 84% of patients normalized their creatinine level within a median time of 10 days (1-77). The most frequent reported Grade 1-4 toxicities were mucositis (84%), gastroenteritis (53%), skin toxicity (34%), colitis (29%), liver toxicity (19%), pneumonitis (5%) and cardiac rhythm disorders (4%). Opportunistic infection was documented in 9.5% of patients, HHV6 reactivation in 6% of patients. Ten percent of patients needed intensive care management and toxic death was estimated at 5% (Table 3). Patients received a median of 3 (0-34) packed red blood cells and 4 (0-56) platelets units. The median time to neutrophils > 0.5 G/L and platelets > 20 G/L were 10 (0-50) and 12 (0-210) days. The median time of hospital stay was 23 (12-85) days. In comparison with the group of patient without renal failure, the group of patients with ARF had older age (58 vs 54), higher rate of pre-transplant chronic renal failure (10% vs 1%), higher rate of platinum treatment (77% vs 64%), higher day1 creatinine level (81 vs 69) and received higher median bendamustine (199 vs 182). Colitis (p=0.039), pneumonitis (p=0.008), cardia arrhythmia (p=160mg/m2 and age were independent prognostic factors for ARF. A three-point clinical predictor score for acute renal failure was identified and included creatinine level>65µmol/l, bendamustine dose >160mg/m² and age>57 years. ARF stratified by score, was 4% with score 0, 17% with score 1, 30% with score 2 and 45% with score 3. In conclusion, BeEAM induced 5% non-relapse mortality with high rate of renal toxicity. A simple, three-point scoring system can stratify patients by levels of risk for ARF. Rapid identification of higher risk patients may allow a reduction of the bendamustine dose to improve clinical outcomes. Prospective comparative studies are needed to confirm toxicity extents of this conditioning as compared with other type of high dose therapy. Disclosures Soussain: Pharmacyclics: Research Funding; Celgene: Research Funding; Roche: Research Funding. Malak:Novartis: Membership on an entity's Board of Directors or advisory committees.

Background There is no standard treatment for R/R MCL that fail first line treatment. Non cross resistant regimens are usually used, which provided sometimes good overall response rate (until 93%) but with a minor disease control (PFS Aim To explore the efficacy of the RiBVD regimen in the salvage therapy setting following failure of one, two or more prior treatments. Methods We proposed to all French LYSA partner centers a survey to retrospectively evaluate the efficacy of the RiBVD regimen in R/R MCL patients, regardless of prior treatments used. The RiBVD regimen comprises : Rituximab 375mg/sqm D1, Bendamustine 90mg/sqm D1 and D2, bortezomib 1,3mg/sqm D1, D4, D8, D11 and dexamethasone 40 mg D2. Analysis was performed in June 2016. Results From January 2012 to December 2015, 49 patients from 17 French hematological centers were recruited to the study. The median age was 72 years (50-91y) with 14 young ( 65y). Thirty eight cases presented with classic MCL variant and 11 had a blastoid variant. All patients but one were CD20+, CD5+, CD10- and were positive CYCLIN D1 expression and/or the t(11;14)(q13;q32). Eighteen patients presented a t(11;14) (q13;q32).The CYCLIN D1 negative patient had a t(11;14). Treatment history: Twenty seven patients received RiBVD in second line, 12 in third line and 10 patients after the third lines. Twenty two patients were refractory to their previous line and 27 were in relapse. Before RiBVD 44/49 patients (90%) had received high dose cytarabine, 3 Ibrutinib and 14 patients were intensified (11 at diagnosis, 3 in relapse). Efficacy: The global overall response rate (ORR) was 75% (37/49, 23 CR and 14 PR). For patients treated in 2nd line, the ORR was 85% (23/27, 16 CR and 7 PR), in 3nd line 58% (7/12, 4 CR and 3 PR), and 70% (7/10) for the others (3 CR and 4 PR). Young patients had an ORR of 64% (9/14, 8 CR, 2 RP) and elderly pts 77% (27/35, 15 CR, 12 PR). For relapsed and refractory pts the ORR was respectively 85% (23/27, 15 CR and 8 PR) and 63% (14/22 with 8 CR and 6 PR). For Classic and blastoid variants the ORR was 81.5% (31/38, 20 CR and 11 PR) and 54% (6/11, 3 CR and 3 PR) respectively. Note that 2/3 pts receiving RiBVD regimen post Ibrutinib failure, reached PR (n=2) and showed stable disease (n=1). Major toxicities were seen in 31 pts (63%) with grade 3/4 hematological toxicity in 22 pts, grade 3 neurotoxicity in 3 pts, grade 3/4 cardiotoxicity in 3 pts, grade 3/4 infectious complications in 8 pts, grade 4 fatigue in 3 pts and grade 3 digestive-tract or cutaneous toxicity in one pt each. At the update point, 17 pts had died, 15 for lymphoma progression, 2 for TRM while experiencing a CR (infectious and leukemia). The follow-up of the 32 surviving pts was 14.5 month. The median PFS was 9 months for the 49 pts. The PFS was statistically affected by the pathologic type (classic vs Blastoid, p=0.03), the number of prior treatment (one vs >one, p=0.04) and response to RiBVD (CR vs PR vs no response, p65) or the state (relapse or refractory) at the time of RiBVD had no impact on PFS. Conclusion The RiBVD regimen which shows remarkable efficacy in frontline treatment of elderly MCL pts, shows potential as a salvage therapy for refractory or relapsed MCL following cytarabine based treatment. This is particularly true for the 47% of patients achieving CR for which 2 years PFS was 71% regardless of their age. 1. Cheah CY, Seymour JF, Wang ML. Mantle Cell Lymphoma. J Clin Oncol 2016; 34: 1256-1269. 2. Gressin R, Callanan M, Daguindau N et al. Frontline therapy with the RiBVD regimen elicits high Clinical and Molecular Response Rates and long PFS in elderly patients Mantle Cell Lymphoma (MCL); Final Results of a Prospective Phase II trial by the LYSA group. Blood 2014. Disclosures No relevant conflicts of interest to declare.

Background Extranodal nasal-type NK/T-cell lymphoma is a rare and severe disease. Considering the rarity of this lymphoma in Europe, we conducted a multicentric retrospective study on nasal-type NK/T cell lymphoma to determine the optimal induction strategy and identify prognostic factors. Methods Thirty-six adult patients with nasal-type NK/T-cell lymphoma were recruited and assessed. In total, 80 % of patients were classified as having upper aerodigestive tract NK/T-cell lymphoma (UNKTL) and 20 % extra-upper aerodigestive tract NK/T-cell lymphoma (EUNKTL). Results For advanced-stage disease, chemotherapy alone (CT) was the primary treatment (84 % vs. 10 % for combined CT + radiation therapy (RT), respectively), while for early-stage disease, 50 % of patients received the combination of CT + RT and 50 % CT alone. Five-year overall survival (OS) and progression-free survival (PFS) rates were 39 % and 33 %. Complete remission (CR) rates were significantly higher when using CT + RT (90 %) versus CT alone (33 %) (p versus 100 % for CT + RT. Quality of response was significantly associated with survival, with 5-year OS being 80 % for CR patients versus 0 % for progressive disease patients (p < 0.01). Conclusion Early RT concomitantly or sequentially with CT led to improved patient outcomes, with quality of initial response being the most important prognosticator for 5-year OS.

Abstract 4336 Background Despite the improvements and promises of novel agents (demethylating and erythropoiesis stimulating agents), red blood cells (RBC) and platelets transfusion remains frequent and essential in the management of myelodysplastic syndromes (MDS). Reducing patients’ dependence to transfusion is a major outcome, linked with the disease prognosis, patients’ quality of life and economical issues. Few data in the literature have described transfusions practices and requirements in MDS patients. We report here an epidemiological study of the transfusion practices in our center and try to build an economical evaluation of direct transfusions costs. Design and Methods We conducted a retrospective, descriptive study including all new patients diagnosed with MDS in the department of haematology of Besan□ on between 2006 and 2009. Patients were classified as high risk (HR) MDS when IPSS was ≥ 1.5, and as low risk (LR) when IPSS was ≤ 1. We compared HR and LR groups and four categories of age (≤68; [68–76]; [76–83] and >83 years) according to transfusion data. The economic study compared direct costs of RBC transfusions and erythroipoiesis-stimulating agents for LR and HR patients, including the costs of hospital stays. Materials, transport, medical examinations, doctors’ and nurses’ wages and iron chelation were not considered in this analysis. T-test and χ2-test were used for comparisons. Results 205 patients were analysed, median age at diagnosis was 74.3 years (table 1), with a predominance of men (sex ratio 1.33). IPSS score was available for 75% of patients (n=154), 111 LR patients and 43 HR patients. Median follow-up was 32 months [10–57]. Twenty-three patients (11%) developed a secondary acute leukaemia and 11 (5%) received allogeneic stem cell transplantation. At diagnosis, hemoglobin (Hb) level was not significantly different between HR and LR patients. Platelets level was lower in the HR vs LR (109 vs. 178 G/L respectively, p Economical analysis showed that annual costs of RBC transfusion were 11,409 euros in LR patients and 21,945 euros in HR patients versus 11,492 euros for EPO. Conclusion In our study, neither transfusion requirement nor transfusion threshold were correlated with age, whereas both were affected by IPSS. Furthermore, age did not appear to be a predictive factor concerning the transfusion dependence. Despite its limits, the economic study reveals that EPO and transfusion's annual costs are similar in low risk patients. Updated data will be presented on EPO and 5-azacytidine use in our cohort to assess their impact on transfusion practices. Disclosures: No relevant conflicts of interest to declare.

Abstract 2679 Extranodal nasal type NK/T-cell lymphoma (ENKTL) is a rare and severe disease, more frequent in Asia and South America. Previous studies showed that the 5-year overall survival (OS) rate was less than 40%, with a progression occurrence within 2 years. The early use of radiotherapy sequentially may cure approximately half of the patients with localized disease. In most patients with advanced disease (stage III/IV), the clinical course is highly aggressive with frequent chemotherapy resistance and a poor prognosis. CHOP-based therapy is frequently used and was associated with poor outcome. Considering the rarity of this lymphoma in Europe, we conducted this retrospective study that represents one of the largest studies of NK/T cell lymphoma 'nasal type'. Between January 1989 and September 2010, 36 patients were recruited with a median age of 49 years (22 to 80). 80% the patients was classified as upper aerodigestive tract NK/T-cell lymphoma (UNKTL) and 20% as extra-upper aerodigestive tract NK/T-cell lymphoma (EUNKTL). 72% of UNKTL patients had a local invasiveness superior to T3. 10 (28%) patients were in stage I, 6 (17%) in stage II and 20 (55%) in stage IV. Most frequent symptoms at diagnosis were obstructive symptomatology, epistaxis or cervical lymphadenopathy. 19 (53%) were in low risk versus 17 (47%) in high risk according to the Korean prognostic index. Chemotherapy (CT) alone was the primary treatment for advanced stage (84% CT and 10% CT+ radiotherapy (RT)) with 82% of patients receiving anthracyclin-based regimen. For the early stage, 50% of patients have received the combination CT plus RT and 50% CT. In the CT group, there was no statistical difference (p=0.77) in the percentage of CR according to the type of regimen. Complete response (CR) was observed in 48% of patient while the other 52% were in less than partial response (PR) or in progressive disease (PD) at the end of treatment. The CR rate was improved with the combination CT+RT (90%) versus 33% with CT alone (p The early use of radiotherapy concomitantly or sequentially with chemotherapy improves the outcome of patients, especially in localized disease but still with aggressive forms in this study. We confirm than quality of initial response is the most important factor for the 5 years overall survival. We think Korean T/NK lymphoma prognostic index to be probably more interesting than IPI score to distinguish high risk group and could be the most appropriate prognostic score for NK/T lymphoma nasal type. Finally, the use of agent like asparaginase in first line should be considered for patients with disseminated disease; this has to be evaluated in prospective trials in order to improve the survival in this disease. Disclosures: Salles: Roche and/or Genetech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genzyme: Membership on an entity's Board of Directors or advisory committees; Calistoga/Gilead: Membership on an entity's Board of Directors or advisory committees.