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Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have both demonstrated impressive clinical activity in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). In this study, we analyzed the outcome of 809 patients with R/R DLBCL after two or more previous lines of treatment who had a commercial chimeric antigen receptor (CAR) T cells order for axi-cel or tisa-cel and were registered in the retrospective French DESCAR-T registry study (NCT04328298). After 1:1 propensity score matching (n = 418), the best overall response rate/complete response rate (ORR/CRR) was 80%/60% versus 66%/42% for patients treated with axi-cel compared to tisa-cel, respectively (P P = 0.0003). Overall survival (OS) was also significantly improved after axi-cel infusion compared to after tisa-cel infusion (1-year OS 63.5% versus 48.8%; HR = 0.63; 95% CI, 0.45–0.88; P = 0.0072). Similar findings were observed using the inverse probability of treatment weighting statistical approach. Grade 1–2 cytokine release syndrome was significantly more frequent with axi-cel than with tisa-cel, but no significant difference was observed for grade ≥3. Regarding immune effector cell-associated neurotoxicity syndrome (ICANS), both grade 1–2 and grade ≥3 ICANS were significantly more frequent with axi-cel than with tisa-cel. In conclusion, our matched comparison study supports a higher efficacy and also a higher toxicity of axi-cel compared to tisa-cel in the third or more treatment line for R/R DLBCL.

Purpose: Patients with Relapsed or Refractory (R/R) Peripheral T cell Lymphomas (PTCL) have a poor prognosis. Bendamustine (B) and Brentuximab Vedotin (Bv) have shown interesting results in this setting. However, little information is available about their efficacy in combination. Patients and Methods: This multicenter and retrospective study aimed to evaluate the efficacy and 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 the overall response rate. Results: Eighty-two patients with R/R PTCL were included. The best ORR was 68%, with 49% of patients in CR. In multivariable analysis, only the relapse status after the last regimen (relapse vs refractory) was associated with the response with an ORR of 83% vs 57% (OR=3.70 (95%CI:1.3-10.5); p=0.014). Median DoR was 15.4 (0.6-50.2) months for patients in CR. With a median follow-up of 22 (0-52) months, the median PFS and OS were 8.3 and 26.3 months respectively. Moreover, patients in CR, who underwent an allogeneic transplant, had a better outcome than patients who did not with a median PFS and OS of 19.3 versus 4.8 months (p=0.0005) and NR versus 12.4 months (p=0.0013) respectively. Fifty-nine percent of patients experienced grade 3/4 adverse events which were mainly hematologic. Conclusion: BBv is highly active in patients with R/R PTCL and should be considered as a one of the best option of immunochemotherapy salvage combination in this setting and particularly as a bridge to allogeneic transplant for eligible patients.

Background: Despite therapeutic progress, 10 to 30% of adult patients with primary mediastinal B cell lymphoma (PMBCL) are primary refractory or experience early relapse (R/R). Allogeneic stem cell transplantation (allo-HSCT) thus remains a potentially curative option in this setting. Material and Methods: In this multicenter retrospective study, the outcomes of 33 French and Belgian adult patients allo-transplanted for R/R PMBCL between January 1999 and December 2018, were examined. Results: At allo-HSCT time, patients had received a median of 3 treatment lines, 50% of them were in complete response, 40% in partial response and 10% had a progressive disease. Forty-two percent of the donors were siblings and 39% matched related. The median follow-up for alive patients was 78 months (3.5-157). Considering the whole cohort, 2-year overall survival (OS), progression free survival (PFS) and graft-versus-host disease-free/relapse-free survival (GRFS) were 48% (95%CI: 33-70), 47% (95%CI: 33-68) and 38.5% (95%CI: 25-60) respectively. Cumulative incidence of relapse and non-relapse mortality rates were respectively 34% (95%CI: 18-50) and 18% (95%CI: 7-34). Disease status at transplant was the only factor predicting survivals, patients with progressive disease showing significant lower 2-year 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). A plateau was observed for OS and PFS after 4 years with 10 patients alive after this date, suggesting that almost one third of the patients effectively salvaged and undergoing allo-SCT could be cured. Conclusion: This study indicates that allo-HSCT is a valid therapeutic option for R/R PMBCL, providing durable remissions.

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.

To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection. In this retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement. The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response. Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML. • Nowadays, PML is emerging as a complication of new effective therapies based on monoclonal antibodies. • Natalizumab-associated PML shows more inflammatory signs, a perivascular distribution “the milky way,” and more cortex involvement than rituximab- and HIV-associated PML. • MRI differences are probably related to higher levels of immunosuppression in HIV patients and those under rituximab therapy.

Background CT and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT performances following immune therapy are not well known in patients with relapsed or refractory Hodgkin lymphoma (RRHL). Purpose To compare CT and PET/CT for prognostic value of early response evaluation following nivolumab therapy. Materials and Methods This retrospective study included patients from 34 institutions who underwent early imaging response evaluation from July 2013 to April 2017. Three experienced readers classified imaging response by using Cheson et al and 2016 Lymphoma Response to Immunomodulatory Therapy Criteria as follows: complete (metabolic) response, partial (metabolic) response, stable disease or no metabolic response, or progressive (metabolic) disease. Primary CT and PET assessments were performed at a median of 2.0 months (interquartile range, 1.7-3.7 months) after nivolumab initiation. Kaplan-Meier analysis was used to determine the relationship of primary CT and PET assessment response categories to overall survival (OS). Agreements between primary and secondary imaging assessments were assessed by using κ analysis. Results A total of 45 patients (median age, 37 years; range, 18-77 years; 25 men) underwent a primary assessment using CT and PET/CT; 36 patients also underwent a subsequent assessment. Eleven patients (24%) died after a median follow-up of 21.2 months. CT and PET response categories were associated with OS (P = .03 for primary CT assessment; P = .02 for primary PET assessment). There was no pseudoprogression at primary CT and PET assessments. At the primary assessment, response categories by using CT were reclassified by using PET in 44% (20 of 45) of patients. Among these, 55% (11 of 20) were reclassified to complete metabolic response (complete metabolic response rate: 29% [13 of 45 patients] vs complete response rate: 4% [two of 45 patients]), with a 2-year OS probability of 100%. At the secondary assessment, complete response rate using CT increased to 17% (six of 36 patients), hence a better agreement with PET (κ = 0.78; P < .001). Conclusion Early CT and PET/CT at a median of 2 months after initiation of nivolumab predicted overall survival in relapsed or refractory Hodgkin lymphoma. Early PET detected additional patients with complete metabolic response. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Scott and Wang in this issue.

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.

We analysed the therapeutic outcomes of all consecutive patients with primary central nervous system lymphoma (PCNSL) registered in the prospective French database for PCNSL and treated with intensive chemotherapy (IC) followed by autologous stem cell transplantation (IC-ASCT) between 2011 and November 2019 (271 patients recruited, 266 analysed). In addition, treatment-related complications of thiotepa-based IC-ASCT were analysed from the source files of 85 patients from 3 centers. Patients had received IC-ASCT either in first-line treatment (n = 147) or at relapse (n = 119). The median age at IC-ASCT was 57 years (range: 22-74). IC consisted of thiotepa-BCNU (n = 64), thiotepa-busulfan (n = 24), BCNU-etoposide-cytarabine-melphalan (BEAM, n = 36) and thiotepa-busulfan-cyclophosphamide (n = 142). In multivariate analysis, BEAM and ASCT beyond the first relapse were adverse prognostic factors for relapse risk. The risk of treatment-related mortality was higher for ASCT performed beyond the first relapse and seemed higher for thiotepa-busulfan-cyclophosphamide. Thiotepa-BCNU tends to result in a higher relapse rate than thiotepa-busulfan-cyclophosphamide and thiotepa-busulfan. This study confirms the role of IC-ASCT in first-line treatment and at first-relapse PCNSL (5-year overall survival rates of 80 and 50%, respectively). The benefit/risk ratio of thiotepa-busulfan/thiotepa-busulfan-cyclophosphamide-ASCT could be improved by considering ASCT earlier in the course of the disease and dose adjustment of the IC.

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.

Background CT and fluorine 18 (

Background Expression of SRY [sex-determining region Y]-box11 (SOX11) is specific to mantle cell lymphoma (MCL) and contributes, in conjunction with immunoglobulin variable heavy chain gene mutation status, to the identification of two forms of this disease. Methods The aim of this report was firstly, to design an easy and suitable RT-qPCR method to quantify SOX11 mRNA expression in mantle cell lymphoma and other B cell malignancies with the proper reference gene; secondly, to define the best threshold of relative quantity of SOX11 mRNA in order to reach the best compromise between sensitivity and specificity. Results For best discrimination of MCL and non-MCL groups we determined an area under the curve (AUC) of 0.9750 and a threshold of 1.76 with 100% sensitivity and 88% specificity. AUC and threshold values of respectively 0.91/1.346 [87% sensitivity, 80% specificity] and 0.9525/1.7120 [100% sensitivity, 88% specificity] for GAPDH and RPLP0 respectively denote that the RPLP0 reference gene alone is sufficient for PCR housekeeping gene. Conclusion This work describes an RT-qPCR assay for SOX11 expression in order to better characterize MCL at diagnosis. Further studies on larger cohorts are needed to evaluate this molecular tool, especially for the follow-up of minimal residual disease. Electronic supplementary material The online version of this article (10.1186/s40164-018-0097-6) contains supplementary material, which is available to authorized users.

Background: The current standard of care for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) is R CHOP; however, approximately 40% of patients are not cured. The CD79b-targeting antibody-drug conjugate, polatuzumab vedotin, is approved in relapsed/refractory DLBCL in combination with bendamustine and rituximab, and has also demonstrated promising first line activity and safety when combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) in a Phase Ib/II study (Tilly, et al. Lancet Oncol 2019). Thus, in the Phase III POLARIX study (NCT03274492) we compared pola-R-CHP with R-CHOP in patients with previously untreated DLBCL. Methods: In this double-blind, placebo-controlled, international study, patients with previously untreated DLBCL and an International Prognostic Index (IPI) of 2-5 were randomized 1:1 to receive six cycles of pola-R-CHP (with a vincristine placebo) or R-CHOP (with a polatuzumab vedotin placebo); all patients also received two additional cycles of rituximab. Patients received polatuzumab vedotin 1.8mg/kg or vincristine 1.4mg/m² administered on Day 1, plus intravenous rituximab 375mg/m2, cyclophosphamide 750mg/m², doxorubicin 50mg/m², and placebo on Day 1, and oral prednisone 100mg once daily on Days 1-5. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included investigator-assessed event-free survival (EFS), independent review committee-assessed complete response (CR) rate at the end of treatment by positron emission tomography-computed tomography (PET-CT), disease-free survival (DFS), overall survival (OS), and safety. Results: Overall, 879 patients were randomized, 440 to pola-R-CHP and 439 to R-CHOP. Median age was 65 (range 19-80) years, and the majority of patients had IPI 3-5 (62.0%). At the data cut-off of June 28, 2021, and after a median follow-up of 28.2 months, PFS was superior with pola-R-CHP vs R CHOP (hazard ratio [HR] 0.73; 95% confidence interval [CI]: 0.57-0.95; P Conclusion: The pola-R-CHP combination demonstrated a 27% reduction in the relative risk of disease progression, relapse, or death compared with R-CHOP, with a similar safety profile in the first-line treatment of patients with DLBCL. Disclosures Tilly: Karyopharm: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Other: Meeting attendance and travel, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Morschhauser: AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; Genentech, Inc.: Consultancy; Janssen: Honoraria; Genmab: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; Incyte: Membership on an entity's Board of Directors or advisory committees. Sehn: Novartis: Consultancy; Genmab: Consultancy; Debiopharm: Consultancy; Teva: Consultancy, Research Funding; Roche/Genentech: Consultancy, Research Funding; AbbVie: Consultancy; Acerta: Consultancy; Amgen: Consultancy; Apobiologix: Consultancy; AstraZeneca: Consultancy; Celgene: Consultancy; Gilead: Consultancy; Incyte: Consultancy; Janssen: Consultancy; Kite: Consultancy; Karyopharm: Consultancy; Lundbeck: Consultancy; Merck: Consultancy; Morphosys: Consultancy; Sandoz: Consultancy; Seattle Genetics: Consultancy; Takeda: Consultancy; TG Therapeutics: Consultancy; Verastem: Consultancy. Friedberg: Bayer: Membership on an entity's Board of Directors or advisory committees; Acerta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Trněný: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Morphosys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Portola: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria. Sharman: AbbVie: Consultancy; AstraZeneca: Consultancy; BeiGene: Consultancy; Bristol-Myers Squibb: Consultancy; Lilly: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy; TG Therapeutics: Consultancy; Centessa: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Velos: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees. Herbaux: Takeda: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria; Janssen: Honoraria. Burke: Verastem: Consultancy; AstraZeneca: Consultancy; Morphosys: Consultancy; Adaptive Biotechnologies: Consultancy; Epizyme: Consultancy; Kura: Consultancy; AbbVie: Consultancy; BeiGene: Consultancy, Speakers Bureau; Kymera: Consultancy; Bristol-Myers Squibb: Consultancy; X4 Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Speakers Bureau; Gilead: Consultancy; Genentech, Inc.: Consultancy. Matasar: Memorial Sloan Kettering Cancer Center: Current Employment; Merck Sharp & Dohme: Consultancy, Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding; GlaxoSmithKline: Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding; IGM Biosciences: Research Funding; Pharmacyclics: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Rocket Medical: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding; ImmunoVaccine Technologies: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Juno Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Teva: Consultancy, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy, Honoraria. Rai: Chugai Pharmaceutical Co., Ltd: Speakers Bureau; ONO Pharmaceutical Co., Ltd: Speakers Bureau; Janssen Pharmaceutical: Speakers Bureau; Eisai Co., Ltd: Speakers Bureau. Izutsu: AbbVie: Honoraria; Allergan Japan: Honoraria; AstraZeneca: Honoraria, Research Funding; Bayer: Research Funding; BeiGene: Research Funding; Celgene: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Fuji Film Toyama Chemical: Honoraria; Genmab: Honoraria, Research Funding; Huya Biosciences: Research Funding; Incyte: Research Funding; Janssen: Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; MSD: Research Funding; Novartis: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Pfizer: Research Funding; Solasia: Research Funding; Symbio: Honoraria; Takeda: Honoraria, Research Funding; Yakult: Research Funding. Mehta-Shah: C4 Therapeutics: Consultancy; Kiowa Hakko Kirin: Consultancy; Karyopharm: Consultancy; Ono Pharmaceuticals: Consultancy; Secura Bio: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; AstraZeneca: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Innate Pharmaceuticals: Research Funding; Roche/Genentech: Research Funding; Corvus Pharmaceuticals: Research Funding; Verastem: Research Funding. Oberic: Celgene: Honoraria; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel; Janssen: Honoraria, Other: Support for attending meetings and/or travel; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel; AbbVie: Other: Support for attending meetings and/or travel; Incyte: Membership on an entity's Board of Directors or advisory committees. Jurczak: Maria Sklodowska-Curie National Research Institute of Oncology: Current Employment; Jagiellonian University: Ended employment in the past 24 months. Greil: Sandoz: Honoraria, Research Funding; Amgen: Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Merck Sharp & Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding. Pinto: Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel; Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel; MSD: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau. Abrisqueta Costa: Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hirata: Genentech, Inc.: Current Employment; Genentech/Roche: Current holder of stock options in a privately-held company. Jiang: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Yan: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Lee: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Flowers: AbbVie: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; BeiGene: Consultancy; Celgene: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Epizyme: Consultancy; Roche/Genentech: Consultancy, Research Funding; Genmab: Consultancy; Gilead: Consultancy, Research Funding; Karyopharm: Consultancy; Pharmacyclics/Janssen: Consultancy; Seattle Genetics: Consultancy; Spectrum: Consultancy; 4D: Research Funding; Acerta: Research Funding; Adaptimmune: Research Funding; Allogene: Research Funding; Amgen: Research Funding; Cellectis: Research Funding; EMD: Research Funding; Guardant: Research Funding; Iovance: Research Funding; Janssen: Research Funding; Kite: Research Funding; Morphosys: Research Funding; Nektar: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; TG Therapeutics: Research Funding; Xencor: Research Funding; Ziopharm: Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; Pharmacyclics: Research Funding. Salles: Bayer: Honoraria; AbbVie: Consultancy, Honoraria; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Debiopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ipsen: Consultancy; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Loxo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Consultancy; Morphosys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rapt: Consultancy, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Honoraria; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Velosbio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Allogene: Consultancy. OffLabel Disclosure: Polatuzumab vedotin is an antibody-drug conjugate targeting CD79b on malignant B-cells. Polatuzumab vedotin in combination with bendamustine and rituximab (pola-BR) improved complete response rate and overall survival compared with BR alone in patients with relapsed/refractory diffuse large B-cell lymphoma. Pola-BR is approved for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, after at least two prior therapies.

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).

Introduction: Primary mediastinal B cell lymphoma (PMBL) is clinically and biologically distinct from the other subtypes of diffuse large B cell lymphoma (DLBCL), typically affecting young female patients (pts) with a bulky mediastinal mass. Standard treatment (TRT) is a combination of anti-CD20 antibody (Ab) and anthracycline-based chemotherapy. We aimed to compare patients' outcomes after CHOP delivered every 21 days (CHOP21) or 14 days (CHOP14) or ACVBP combined with anti-CD20 Ab in real life. Methods: All Pts treated in LYSA centers were eligible in this retrospective analysis. Inclusion criteria were as follow: age ≥18 years (yrs), newly diagnosed PMBL, TRT with CHOP or ACVBP plus anti-CD20 Ab between 2006 and 2017, and patient non-opposition statement. Primary endpoint was progression-free survival (PFS), secondary endpoints were: overall survival (OS), response rate (Lugano 2014) and total metabolic tumor volume (TMTV). Results: 313 pts were enrolled from 25 LYSA centers in France and Belgium. In all, median age at diagnosis was 32 (18-88) yrs. Majority of pts were female pts (60.7%) and presented at diagnosis with a good performance status (0-1: 81.8%), stage I-II (57.5%), elevated LDH (85%), Bulk>10cm (58.5%) and low/low-intermediate aaIPI 0-1 (56.7%). Pts in the CHOP21 (n=57) group were older (median 40 yrs, vs 33 vs 29.5, p Complete metabolic response rates at end of TRT were comparable between CHOP21, CHOP14 and ACVBP groups: 81.1%, 90.9%, and 85.5%, respectively (p=0.46). 37 (11.8%) pts progressed including 32 (10.2%) who displayed primary refractory disease and 6 (16.2%) pts who relapsed after consolidation ASCT. CNS relapse occurred in 9 (2.9%) pts. Median time between ASCT and relapse was 3 (2-58) months. Patients received the following salvage TRTs: high dose chemotherapy (HDC: R-ICE/R-DHAOX-like) (n=30) followed by second-line consolidation ASCT (n=11/30) and post-ASCT mediastinal RT (n=5/11); salvage RT without chemotherapy (n=1); other regimens (R-CHOP, R-GEMOX) (n=3); none (n=3). 2-yrs second PFS (PFS2) rates in pts who had previously received CHOP21, CHOP14 and ACVBP were: 20.5% vs 62.5% vs 18.8% (p=0.43). Only HDC + ASCT strategy granted disease control (2-yrs PFS2: 32.3%). Median follow up was 44 (1-153) months and the CHOP21, CHOP14, ACVBP 5-yrs PFS and 5-yrs OS were: 74.7% (95%CI: 64-97.1%), 89.4% (82.7-96.6%), 89.4% (84.8-94.2%) (p=0.018, Figure A); and 81% (70-94.4%), 100% (100-100%), 92.4% (88.4-96.7%) (p=0.0036, Figure B), respectively. In a multivariate model including TRT group, consolidation ASCT and/or RT, aaIPI, Bulk>10cm and TMTV≥360cm3, CHOP14 was not associated with better PFS as compared to ACVBP and CHOP21 (p=0.1548). Baseline higher TMTV (≥ 360 cm3) was associated with lower PFS in multivariate analysis, independently of TRT (HR=0.41 [0.2-0.85], p=0.02). All grades TRT-related adverse events were similar between the groups, except for an excess of febrile neutropenia (5.3% vs 5.3% vs 24.4%, p Conclusion These results confirm the favorable outcome of PMBL pts treated with CHOP14 and ACVBP plus anti CD20 Ab. The toxicity of ACVBP was more pronounced and CHOP14 was associated with a better OS. Baseline TMTV≥360cm3 is a highly predictive factor of unfavorable outcome in PMBL pts, independently of TRT. We recommend R-CHOP14 as standard of care in PMBL. Figure Disclosures Camus: ROCHE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); PFIZER: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); AMGEN: Honoraria; JANSSEN: Honoraria. Decazes:Bayer: Other: travel, accomodations, expenses. Bernard:Janssen: Other: Travel and accommodation . Gandhi Laurent:Abbevie, Pfizer, Takeda, Roche: Other: Travel; Roche, Takeda, Iqone, Accord: Consultancy; Roche, Takeda, Accord: Honoraria. Laribi:amgen: Research Funding; novartis: Honoraria, Research Funding; takeda: Research Funding; abbvie: Honoraria, Research Funding. Houot:Gilead: Honoraria; Kite: Honoraria; Roche: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; MSD: Honoraria. Tilly:BMS: Honoraria.

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.

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

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.