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International audience; Criteria based on measurements of lesion diameter at CT have guided treatment with historical therapies due to the strong association between tumor size and survival. Clinical experience with immune checkpoint modulators shows that editing immune system function can be effective in various solid tumors. Equally, novel immune-related phenomena accompany this novel therapeutic paradigm. These effects of immunotherapy challenge the association of tumor size with response or progression and include risks and adverse events that present new demands for imaging to guide treatment decisions. Emerging and evolving approaches to immunotherapy highlight further key issues for imaging evaluation, such as dissociated response following local administration of immune checkpoint modulators, pseudoprogression due to immune infiltration in the tumor environment, and premature death due to hyperprogression. Research that may offer tools for radiologists to meet these challenges is reviewed. Different modalities are discussed, including immuno-PET, as well as new applications of CT, MRI, and fluorodeoxyglucose PET, such as radiomics and imaging of hematopoietic tissues or anthropometric characteristics. Multilevel integration of imaging and other biomarkers may improve clinical guidance for immunotherapies and provide theranostic opportunities.

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.

Objectives Cancer patients with pre-existing autoimmune disease, such as systemic sclerosis (SSc), are excluded from clinical trials, so the data on tolerability and efficacy of immune checkpoint inhibitors in these patients are limited. This study investigated the tolerability and efficacy of anti–programmed death ligand 1 (PD (L)1) immunotherapies in patients with pre-existing SSc. Methods Scleronco-01 was a multicentre, nationwide, open-label, phase IV observational study, from 2019 to 2021. Results Seventeen SSc patients receiving treatment for lung carcinoma (n = 13, 77%), head and neck cancer (n = 2, 12%), melanoma (n = 1, 6%), and colorectal carcinoma (n = 1, 6%) were included. The median (interquartile range) patient age was 60 (34–82) years. Fifteen (88%) patients received anti-PD1 (nivolumab and pembrolizumab) and two (12%) anti-PD-L1 (durvalumab). The median follow-up duration was 12 (range, 2–38) months. Four patients (24%) experienced flare-up of SSc symptoms. Ten patients (59%) developed an immune-related adverse event (grade I–II in 11 patients [65%], grade III–IV in one [6%]) without grade V. The overall response rate was 41% (7/17 patients). The median overall survival was 15.8 (95% confidence interval: 7.3 to not reached) months. Conclusion Anti-PD1 or PD-L1 immunotherapies are suitable options for cancer patients with pre-existing SSc. Longer follow-up periods are required for long-term safety analyses.

SummaryDiffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) are the two most common B-cell lymphomas and are characterized by a dynamic crosstalk between tumor B cells and a heterogeneous tumor-supportive microenvironment, including immune, endothelial, and stromal components. Although their impact on the pathogenesis and prognosis of B-cell lymphoma has been acknowledged for years, tumor-associated macrophages (TAM) have not been extensively explored in DLBCL and FL. Herein, we investigate mononuclear phagocytes (MNP) heterogeneity at the single cell level and their potential co-regulation with the stromal and endothelial compartments in B-cell lymphoma lymph nodes compared to reactive secondary lymphoid organs, using a combination of mass cytometry, single cell RNA sequencing, andin silicoapproaches. We reveal a co-regulation between TAM and blood endothelial cells (BEC) in lymphoma. Moreover, we identify a specific interaction between Annexin A1 (ANXA1)-expressing BEC and formyl-peptide receptors (FPR1/2)-expressing monocytes/macrophages in DLBCL, which we confirmin situby multiplex immunofluorescence and imaging mass cytometry. This crosstalk is associated to an immunosuppressive tumor microenvironment and an adverse prognosis in DLBCL.

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.

Composite and sequential lymphomas involving both classical Hodgkin lymphoma (CHL) and primary mediastinal B-cell lymphoma (PMBCL) are rare phenomena. Beyond the relevant biological interest raised by these cases, treatments and outcome data are poorly covered in the recent literature. This retrospective analysis describes the pathological and clinical characteristics of 10 composite and 15 sequential cases included after a central pathological review. At diagnosis, 70% of the composite lymphomas presented a disseminated and extranodal disease. Among the 15 sequential lymphomas, 12 were CHL at first occurrence and three were PMBCL. Based on their clinical evolution, these sequential lymphomas could be divided into early (i.e., diagnosis of second lymphoma within a year) and late [(i.e., a second lymphoma occurrence occurring after a long period of complete remission]). All composite cases were alive in complete remission after a median follow-up of 34 months. If the early sequential lymphoma presented a particularly poor outcome with a median overall survival shorter than one year, the late cases were efficiently salvaged. Further molecular studies are needed to describe the underlying biology of these rare diseases, possibly representing the extreme of tumour cell plasticity found in grey-zone lymphoma.

International audience; The development of immunotherapy has revolutionized cancer treatment, improving the outcome and survival of many patients. Immune checkpoint inhibitors (ICIs), the most common form of immunotherapy, use antibodies to restore T-cells' anti-tumor activity. Immune checkpoint inhibitors are gaining ground in the therapeutic strategy across various cancers. Although widely used in solid tumors, ICIs have shown remarkable efficacy in patients with Hodgkin lymphoma. 2-[F-18]Fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/CT is the gold standard to stage and monitor responses in Hodgkin lymphoma. This article reviewed the use of 2-[F-18]FDG-PET/CT in patients with Hodgkin lymphoma treated with ICI, focusing on image interpretation for response monitoring and detecting adverse events.

The development of immunotherapy has revolutionized cancer treatment, improving the outcome and survival of many patients. Immune checkpoint inhibitors (ICIs), the most common form of immunotherapy, use antibodies to restore T-cells' anti-tumor activity. Immune checkpoint inhibitors are gaining ground in the therapeutic strategy across various cancers. Although widely used in solid tumors, ICIs have shown remarkable efficacy in patients with Hodgkin lymphoma. 2-[

International audience; Anti-PD-1 monoclonal antibodies yield high response rates in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but most patients will eventually progress. Allogeneic hematopoietic cell transplantation (alloHCT) after PD-1 blockade may be associated with increased toxicity, raising challenging questions about the role, timing, and optimal method of transplantation in this setting. To address these questions, we assembled a retrospective cohort of 209 cHL patients who underwent alloHCT after PD-1 blockade. With a median follow-up among survivors of 24 months, the 2-year cumulative incidences (CIs) of non-relapse mortality and relapse were 14 and 18%, respectively; the 2-year graft-versus-host disease (GVHD) and relapse-free survival (GRFS), progression-free survival (PFS), and overall survival were 47%, 69%, and 82%, respectively. The 180-day CI of grade 3-4 acute GVHD was 15%, while the 2-year CI of chronic GVHD was 34%. In multivariable analyses, a longer interval from PD-1 to alloHCT was associated with less frequent severe acute GVHD, while additional treatment between PD-1 and alloHCT was associated with a higher risk of relapse. Notably, post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis was associated with significant improvements in PFS and GRFS. While awaiting prospective clinical trials, PTCy-based GVHD prophylaxis may be considered the optimal transplantation strategy for this patient population.

Simple Summary B-cell non-Hodgkin lymphomas (NHL) include many diseases with distincts pathogenic mechanisms, prognoses and management. Most patients benefit generally from efficient therapies allowing cure or prolonged remission. However, when they are refractory or relapse after standard therapy, they harbor a poor prognosis. In last decades, numerous novel immunotherapies have been developed with the aim of redirecting T-cell specificity against tumor antigens. Latest data on CAR T-cells confirm their efficacy and their safety in this setting. In addition, trials with bispecific antibodies are also ongoing for these patients, with encouraging premiminary findings, whether before or after CAR T-cells treatment. Here, we review the main results of CAR T-cells and bispecific T-cell engagers studies in the B-cell non-Hodgkin lymphomas setting. These advances in immunotherapies have transformed diffuse large B-cell lymphomas prognosis and will process indolent NHL’s future. Results with such treatments could lead to a new standard of care for those patients who are often heavily pretreated. Abstract T-cell specificity can be redirected against tumor antigens either ex vivo using engineered chimeric antigen receptor (CAR) T-cells or in vivo by bridging natural T-cells and tumor cells with bispecific T-cell engager (TCE) antibodies. Currently, four CAR T-cells have been approved by the FDA for the treatment of B-cell lymphomas, including diffuse large B cell lymphomas (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL). No TCE have yet been approved for the treatment of B-cell lymphomas. However, at least four of them are in clinical development and show promising activity. Here, we review the most recent advances of CAR T-cells and TCE in the treatment of B-cell lymphomas.

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.

International audience; Introduction - Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti-PD1 therapy. In these patients, the optimal duration of treatment and the risk of relapse after anti-PD1 discontinuation are unknown. Methods - We retrospectively analyzed patients with R/R HL who responded to anti-PD1 monotherapy and discontinued the treatment either because of unacceptable toxicity or prolonged remission. A machine learning algorithm based on 17 candidate variables was trained and validated to predict progression-free survival (PFS) landmarked at the time of discontinuation of anti-PD1 therapy. Results - Forty patients from 14 centers were randomly assigned to training (n = 25) and validation (n = 15) sets. At the time of anti-PD1 discontinuation, patients had received treatment for a median duration of 11.2 (range, 0-time to best response was not statistically significant in discriminating patients with PFS lesser or greater than 12 months). Considering PFS status as a binary variable (alive or dead) at a specific time point (12 months) is convenient, intuitive and allows for comparing the value of potential predicting variables in these two groups of patients. Nonetheless, this approach has two drawbacks: first, it binarizes outcome; second, it excludes patients alive with a time to last follow up lesser 12 months. Therefore, it is less powerful to demonstrate statistically significant association with PFS even if it exists 5 months. Patients discontinued anti-PD1 treatment either because of prolonged remission (N = 27, 67.5%) or unacceptable toxicity (N = 13, 32.5%). Most patients were in CR (N = 35, 87.5%) at the time of anti-PD1 discontinuation. In the training set, the machine learning algorithm identified that the most important variables to predict PFS were patients' age, time to best response, and presence or absence of CR. The performance observed in the training set was validated in the validation set. Conclusion - In this pilot, proof of concept study using a machine learning algorithm, we identified biomarkers capable of predicting the risk of relapse after anti-PD1 discontinuation (age, time to best response, quality of response). Once confirmed, these simple biomarkers will represent useful tools to guide the management of these patients.

Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are heterogeneous cells that share myeloid markers and are not easily distinguishable in human tumors due to their lack of specific markers. These cells are a major player in the tumor microenvironment and are involved in the prognosis and physiopathology of various tumors. Here is presented a scheme to decipher these cells by mass cytometry.

Background CT and fluorine 18 (

International audience; Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti-PD1 therapy. In these patients, there is limited data about the optimal duration of treatment and the risk of relapse after anti-PD1 discontinuation. We have previously reported the outcome of 11 patients with R/R HL who discontinued anti-PD1 therapy after achieving a complete response (CR) upon nivolumab1 . These patients experienced favorable outcome as only 2 of them had relapsed after a median follow-up of 21.2 months from discontinuation. Despite the low relapse rate observed in that study, physicians may be worried about the possibility to further rescue these heavily pre-treated patients in case of relapse after anti-PD1 discontinuation. Notably, it is still unknown whether these patients will remain sensitive to a 2nd course of anti-PD1.

International audience; Introduction: Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti-PD1 therapy. In these patients, the optimal duration of treatment and the risk of relapse after anti-PD1 discontinuation are unknown.Methods: We retrospectively analyzed patients with R/R HL who responded to anti-PD1 monotherapy and discontinued the treatment either because of unacceptable toxicity or prolonged remission. A machine learning algorithm based on 17 candidate variables was trained and validated to predict progression-free survival (PFS) landmarked at the time of discontinuation of anti-PD1 therapy.Results: Forty patients from 14 centers were randomly assigned to training (n = 25) and validation (n = 15) sets. At the time of anti-PD1 discontinuation, patients had received treatment for a median duration of 11.2 (range, 0-time to best response was not statistically significant in discriminating patients with PFS lesser or greater than 12 months). Considering PFS status as a binary variable (alive or dead) at a specific time point (12 months) is convenient, intuitive and allows for comparing the value of potential predicting variables in these two groups of patients. Nonetheless, this approach has two drawbacks: first, it binarizes outcome; second, it excludes patients alive with a time to last follow up lesser 12 months. Therefore, it is less powerful to demonstrate statistically significant association with PFS even if it exists 5 months. Patients discontinued anti-PD1 treatment either because of prolonged remission (N = 27, 67.5%) or unacceptable toxicity (N = 13, 32.5%). Most patients were in CR (N = 35, 87.5%) at the time of anti-PD1 discontinuation. In the training set, the machine learning algorithm identified that the most important variables to predict PFS were patients' age, time to best response, and presence or absence of CR. The performance observed in the training set was validated in the validation set.Conclusion: In this pilot, proof of concept study using a machine learning algorithm, we identified biomarkers capable of predicting the risk of relapse after anti-PD1 discontinuation (age, time to best response, quality of response). Once confirmed, these simple biomarkers will represent useful tools to guide the management of these patients.

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

International audience; BACKGROUND:Paraneoplastic syndromes (PNS) are autoimmune disorders specifically associated with cancer. There are few data on anti-PD-1 or anti-PD-L1 immunotherapy in patients with a PNS. Our objective was to describe the outcome for patients with a pre-existing or newly diagnosed PNS following the initiation of anti-PD-1 or anti-PD-L1 immunotherapy.METHODS:We included all adult patients (aged ≥18) treated with anti-PD-1 or anti-PD-L1 immunotherapy for a solid tumor, diagnosed with a PNS, and registered in French pharmacovigilance databases. Patients were allocated to cohorts 1 and 2 if the PNS had been diagnosed before vs. after the initiation of immunotherapy, respectively.FINDINGS:Of the 1304 adult patients screened between June 27th, 2014, and January 2nd, 2019, 32 (2.45%) had a PNS and were allocated to either cohort 1 (n = 16) or cohort 2 (n = 16). The median (range) age was 64 (45-88). The tumor types were non-small-cell lung cancer (n = 15, 47%), melanoma (n = 6, 19%), renal carcinoma (n = 3, 9%), and other malignancies (n = 8, 25%). Eleven (34%) patients presented with a neurologic PNS, nine (28%) had a rheumatologic PNS, eight (25%) had a connective tissue PNS, and four (13%) had other types of PNS. The highest severity grade for the PNS was 1-2 in 10 patients (31%) and ≥ 3 in 22 patients (69%). Four patients (13%) died as a result of the progression of a neurologic PNS (encephalitis in three cases, and Lambert-Eaton syndrome in one case). Following the initiation of immunotherapy, the PNS symptoms worsened in eight (50%) of the 16 patients in cohort 1.INTERPRETATION:Our results show that PNSs tend to be worsened or revealed by anti-PD-1 or anti-PD-L1 immunotherapy. Cases of paraneoplastic encephalitis are of notable concern, in view of their severity. When initiating immunotherapy, physicians should carefully monitor patients with a pre-existing PNS.

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.

To the editor: Anti-programmed cell death protein 1 (anti-PD-1) antibodies demonstrated remarkable efficacy in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL). In the 2 largest prospective studies that evaluated the anti-PD-1 antibodies nivolumab (CHECKMATE-205)[1][1] and

International audience

International audience; The article by Rivera et al is the first report of a previously undescribed side effect of checkpoint inhibitors: hair repigmentation (HR). In this significant case series of 14 patients, all patients received an anti–programmed cell death 1 (PD-1) and anti–programmed cell death 1 ligand 1 (PD-L1) antibody for the treatment of a lung cancer...

International audience; The paradigm of response in Hodgkin lymphoma (HL) was developed in cytotoxic chemotherapies and its use as a reference model for immune-modulatory regimens, which restores the immune system's anti-tumor capacity, is questioned.

Introduction: Anti-PD-1 monoclonal antibodies (mAbs) are highly active in relapsed/refractory classical Hodgkin lymphoma (cHL), but most patients (pts) will still relapse. Given this, allogeneic stem cell transplantation (alloHSCT) remains an important option for pts after PD-1 blockade, as it offers the possibility of cure. Prior reports have suggested that alloHSCT after PD-1 mAbs may be associated with severe immune-related complications including acute graft-versus-host disease (GVHD), veno-occlusive disease (VOD) and cytokine release/febrile non-infectious syndrome (CRS). Prior studies of alloHSCT after PD-1 blockade in cHL have been limited by the small number of pts and short follow-up, preventing an accurate assessment of long-term outcomes and complications, risk factors for early toxicity, and the impact of transplant strategies such as choice of GVHD prophylaxis. We therefore assembled a large retrospective international cohort of cHL pts who underwent alloHSCT after PD-(L)1 blockade to better answer these questions, including an assessment of the impact of post-transplant cyclophosphamide (PTCy) on efficacy and toxicity. Methods: Medical records and databases were reviewed at 26 European and United States transplant centers to identify pts with cHL who underwent an alloHSCT any time after receiving a PD-1 or PD-L1 mAb. Response assessment was performed by local investigators according to Lugano 2014 criteria. Overall survival (OS), progression-free survival (PFS), cumulative incidence (CumInc) of relapse (CIR), non-relapse mortality (NRM), acute (a) and chronic (c) GVHD were estimated, as was the association between baseline variables and these outcomes. Results: Between 2014 and 2019, 150 pts were identified who underwent alloHSCT after a median of 10 (range, 1-74) doses of nivolumab (n=118), pembrolizumab (n=31), or avelumab (n=1). The median age was 31 (range 17-68) and pts had received a median of 4 (range, 2-11) lines of therapy prior to PD-(L)1 blockade. 138 pts (92%) had failed BV and 111 (74%) autologous HSCT. The best overall response to PD-(L)1 mAbs was CR for 62 pts (41%), PR for 55 (37%), SD for 17 (11%), PD for 15 (10%) and unknown for 1 (1%). Median time from last dose of PD-(L)1 mAb to alloHSCT was 80 days (range, 17-756) with 70 pts (47%) receiving intervening systemic therapy. At alloHSCT, 90 pts were in CR (60%), 45 in PR (30%), 5 in SD (3%), and 10 in PD (7%). Donors were haploidentical (n=71, 47%), matched sibling (n=29, 19%), matched unrelated (n=39, 26%), mismatched unrelated (n=7, 5%), cord blood (n=2, 1%), or unknown (n=2, 1%). Stem cell source was bone marrow (n=38, 25%), peripheral blood (n=110, 73%), or cord blood (n=2, 1%). GVHD prophylaxis included PTCy in 88 pts (59%) (69/71 (97%) with haploidentical donors; 19/79 (24%) with other donors). With a median post-alloHSCT follow-up for survivors of 23.8 months (range, 1-67), the 2y OS and PFS were 79% (95CI 71-86%) and 65% (95CI 55-73%), respectively, while the 2y CumIncs of relapse and NRM were 21% (95CI 13-29%) and 14%, (95CI, 8-22%), respectively (Fig. 1A-B). 27 pts have died, 3 due to disease and 24 to NRM, including aGVHD (n=7) and VOD (n=2). Veno-occlusive disease (VOD) occurred in 5 pts (day 100 CumInc 4%) and 29 pts (19%) developed CRS (grade 1 n=16; grade 2 n=7; grade 3 n=4; grade 4 n=2). The 6-month CumIncs of grade 2-4, grade 3-4 and grade 4 aGVHD were 39%, 16% and 8%, respectively. Hyperacute GVHD (onset ≤ 14 days after alloHSCT) occurred in 4% of pts and was fatal in 2 pts. The 2y CumInc of cGVHD was 45%. Neither receipt of > 10 doses (median) of anti-PD-(L)1 mAb nor undergoing alloHSCT ≤80 days (median) after last dose of PD-(L)1 mAb were associated with PFS or OS. However, pts with a shorter time to transplant (≤80 days) appeared to have a higher risk of severe (grade 3-4) aGVHD (6m CumInc 24% vs 9%, p=0.006). Recipients of PTCy in this cohort had lower 2y CumIncs of cGVHD (34% vs 58%, p=0.01) and relapse (12% vs 31%, p=0.02), superior 2y PFS (76% vs 54%, p=0.015), and similar rates of severe aGVHD (15% vs 18%, p=0.5), 2y NRM (12% vs 16%, p=0.5), and 2y OS (82% vs 78%, p=0.6). Conclusions: With extended follow-up of a large international cohort, our results argue that alloSCT performed after PD-(L)1 mAbs is a feasible strategy associated with an excellent PFS and a very low CIR for this disease. The use of PT-Cy appears to be associated with improved outcomes and may at present represent the optimal transplant strategy in this pt population. Figure Disclosures Corradini: kite: Honoraria; Abbvie: Honoraria; Servier: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Roche: Honoraria; Novartis: Honoraria; KiowaKirin: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Daiichi Sankyo: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Ho:Jazz Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Consultancy; Omeros Corporation: Membership on an entity's Board of Directors or advisory committees. Jaglowski:Kite: Consultancy, Other: advisory board, Research Funding; Novartis: Consultancy, Other: advisory board, Research Funding; Juno: Consultancy, Other: advisory board; Unum Therapeutics Inc.: Research Funding. Herrera:Adaptive Biotechnologies: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; AstraZeneca: Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Kite Pharma: Consultancy, Research Funding. Blaise:Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria; Molmed: Consultancy, Honoraria. Hamadani:Pharmacyclics: Consultancy; Sanofi Genzyme: Research Funding, Speakers Bureau; Merck: Research Funding; Otsuka: Research Funding; Janssen: Consultancy; Medimmune: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy. Ansell:LAM Therapeutics: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Affimed: Research Funding. Nieto:Astra-Zeneca: Research Funding; Affimed: Consultancy; Affimed: Research Funding; Novartis: Research Funding. Feldman:Celgene: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Pfizer: Research Funding; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Portola Pharma: Research Funding; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Kyowa Hakko Kirin: Research Funding; Eisai: Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Cell Medica: Research Funding; Roche: Research Funding; Corvus: Research Funding; Viracta: Research Funding; Trillium: Research Funding; Roche: Research Funding; Takeda: Honoraria, Speakers Bureau. McGuirk:ArticulateScience LLC: Other: Assistance with manuscript preparation; Bellicum Pharmaceuticals: Research Funding; Kite Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gamida Cell: Research Funding; Pluristem Ltd: Research Funding; Juno Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Research Funding; Novartis: Research Funding; Fresenius Biotech: Research Funding. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Stamatoulas Bastard:Celgene: Honoraria; Takeda: Consultancy. Houot:Bristol Myers Squibb: Honoraria; Merck Sharp Dohme: Honoraria. Manson:Bristol Myers Squibb: Honoraria. Orvain:Incyte: Honoraria; Novartis: Honoraria; Jazz Pharmaceuticals: Other: Travel & accommodations; Pfizer: Other: Travel & accommodations. Bouabdallah:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Frigault:Novartis: Consultancy; Kite/Gilead: Honoraria; Nkarta: Consultancy; Incyte: Consultancy; Juno/Celgene: Consultancy; Foundation Medicine: Consultancy; Xenetic: Consultancy. Chen:Takeda: Consultancy; Kiadis: Consultancy; Magenta: Consultancy; Abbvie: Consultancy; Incyte: Consultancy. Lynch:T.G. Therapeutics: Research Funding; Rhizen Pharmaceuticals S.A: Research Funding; Takeda Pharmaceuticals: Research Funding; Juno Therapeutics: Research Funding; Incyte Corporation: Research Funding; Johnson Graffe Keay Moniz & Wick LLP: Consultancy. Smith:AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck Sharp & Dohme Corp: Consultancy, Research Funding; Acerta Pharma BV: Research Funding; Portola Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; Bristol-Myers Squibb (spouse): Research Funding; Denovo Biopharma: Research Funding; Genentech: Research Funding; Ignyta (spouse): Research Funding; Incyte Corporation: Research Funding; Ayala (spouse): Research Funding; Seattle Genetics: Research Funding. Byrne:Karyopharm: Research Funding. Cohen:Hutchison: Research Funding; Astra Zeneca: Research Funding; Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; Genentech, Inc.: Consultancy, Research Funding; UNUM: Research Funding; ASH: Research Funding; LAM Therapeutics: Research Funding; Lymphoma Research Foundation: Research Funding. Svoboda:AstraZeneca: Consultancy; Celgene: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Kyowa: Consultancy; Merck: Research Funding; BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. Santoro:Bayer: Consultancy, Speakers Bureau; MSD: Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau; Takeda: Speakers Bureau; BMS: Speakers Bureau; Roche: Speakers Bureau; Abb-Vie: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau; BMS: Consultancy; Lilly: Speakers Bureau; Sandoz: Speakers Bureau; Eisai: Consultancy, Speakers Bureau. Armand:Sigma Tau: Research Funding; Otsuka: Research Funding; Pfizer: Consultancy; ADC Therapeutics: Consultancy; Tensha: Research Funding; Affimed: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Infinity: Consultancy; Genentech: Research Funding. Zinzani:Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Honoraria, Speakers Bureau. Carlo-Stella:Servier: Consultancy, Honoraria, Other: Travel, accommodations; Genenta Science srl: Consultancy; Boehringer Ingelheim: Consultancy; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; Novartis: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Sanofi: Consultancy, Research Funding; Rhizen Pharmaceuticals: Research Funding; Celgene: Research Funding; Amgen: Honoraria; AstraZeneca: Honoraria; Janssen Oncology: Honoraria; MSD: Honoraria; BMS: Honoraria; Janssen: Other: Travel, accommodations; Takeda: Other: Travel, accommodations.

Introduction Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti-PD1 therapy. In these patients, the optimal duration of treatment and the risk of relapse after anti-PD1 discontinuation are unknown. Furthermore, the efficacy of anti-PD1 re-treatment in patients who relapse after anti-PD1 discontinuation remains to be determined. Here, we investigated the risk of relapse in patients who responded to anti-PD1 therapy and discontinued the treatment, as well as the efficacy of anti-PD1 re-treatment in patients who relapsed after anti-PD1 discontinuation. Methods We retrospectively analyzed patients with R/R HL who responded to anti-PD1 monotherapy (concomitant radiotherapy was permitted) and discontinued the treatment either because of unacceptable toxicity or prolonged remission (based on the clinician's decision). Patients who discontinued because of relapse/progression or underwent consolidation with allogenic stem cell transplantation [alloSCT] were not included. A random forest machine-learning algorithm was trained to predict relapse using 14 candidate biomarkers. Finally, we analyzed the outcome of patients who relapsed after anti-PD1 discontinuation and their response to anti-PD1 re-treatment. Results We included 32 patients from 13 Centers in France, Portugal and Belgium. Patients' characteristics are summarized in Table 1. At the time of anti-PD1 discontinuation, patients had received either nivolumab (N=27, 84.4%) or pembrolizumab (N=5, 12.5%) for a median duration of 14.6 (range, 0-33.5) months. Patients discontinued anti-PD1 treatment either because of prolonged remission (N=23, 71.9%) or unacceptable toxicity (N=9, 28.1%). Most patients were in CR (N=29, 90.1%) at the time of anti-PD1 discontinuation. After a median follow-up of 20.8 months (range, 0.7-47.6) from anti-PD1 discontinuation, 21 (65.6%) patients had not relapsed/progressed. All 3 patients who were in PR at the time of anti-PD1 discontinuation had relapsed. Among the 29 patients who were in CR at the time of anti-PD1 discontinuation, the estimated disease-free survival was 64.3% (CI 95, 46.6-88.7%) at 24 months (Figure 1). Three patients died: two from disease progression and one from severe GVHD while in CR. Interestingly, 4 patients remain in CR more than 3 years after anti-PD1 discontinuation although these patients had received only short courses of anti-PD1 ( Among the 11 patients who relapsed, 7 were re-treated with (the same) anti-PD1 (Figure 2). Five achieved a CR, 1 achieved a PR and one patient has not been evaluated yet (but is in clinical response). Conclusion A significant proportion of patients experience prolonged remissions after anti-PD1 discontinuation and thus might be cured. Using a machine-learning algorithm, we identified biomarkers capable of predicting the risk of relapse after anti-PD1 discontinuation. These biomarkers are currently being validated in an independent set of patients. Finally, among patients who relapse after anti-PD1 discontinuation, re-treatment with anti-PD1 appears to be efficient. Disclosures Manson: Bristol Myers Squibb: Honoraria. Brice:Takeda France: Consultancy, Honoraria; Millennium Takeda: Research Funding; BMS: Honoraria. Herbaux:Janssen: Honoraria; BMS: Honoraria; Takeda: Honoraria; Abbvie: Honoraria; Gilead: Honoraria. Silva:Abbvie Inc: Consultancy; Celgene: Consultancy; Gilead Sciences: Consultancy, Research Funding; Janssen Cilag: Consultancy; Roche: Consultancy. Stamatoulas Bastard:Celgene: Honoraria; Takeda: Consultancy. Houot:Bristol Myers Squibb: Honoraria; Merck Sharp Dohme: Honoraria.

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

International audience; Checkpoint inhibitors (CPI), namely anti-CTLA4 and anti-PD1/PD-L1 antibodies, demonstrated efficacy across multiple types of cancer. However, only subgroups of patients respond to these therapies. Additionally, CPI can induce severe immune-related adverse events (irAE). Biomarkers that predict efficacy and toxicity may help define the patients who may benefit the most from these costly and potentially toxic therapies. In this study, we review the main biomarkers that have been associated with the efficacy (pharmacodynamics and clinical benefit) and the toxicity (irAE) of CPIs in patients.

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

BACKGROUND: It has been recently shown that nivolumab, a programmed death 1 (PD-1) blocking antibody, had substantial therapeutic activity and an acceptable safety profile in patients with relapsed or refractory Hodgkin's lymphoma (HL). To our knowledge, this drug has never been tested after allogeneic stem cell transplantation (allo-SCT) mainly because PD-1-blocking strategy may substantially increase the risk of Graft Versus Host Disease (GVHD). Nevertheless, some studies suggested that Reed-Sternberg cells exploit the PD-1 pathway to evade immune detection, possibly explaining why some patients resist to graft-versus-lymphoma effect. PATIENTS AND METHODS: We retrospectively assessed the efficacy and toxicity of nivolumab as a single agent in 12 HL patients relapsing after allo-SCT. All patients had progressive disease at the nivolumab initiation. The dose was 3 mg/kg of body weight every 2 weeks. The median of previous systemic therapies was 9 (range 7-11), including allo-SCT. Patients were required to be off immune suppression for more than 4 weeks prior to nivolumab initiation, with no history of grades III-IV acute or extensive chronic GVHD. Toxicities were graded according to the National Cancer Institute Common Toxicity Criteria for AEs (version 4.0). Efficacy was assessed by physical examination before each infusion and per IWG guidelines (Cheson 2007) after four injections of nivolumab. RESULTS: Eight out of 12 patients were evaluable at the time of submission. Median age at time of transplant was 31 (range 28-42) and median time from allo-SCT to study treatment was 11 months (range 3 - 122). Eight patients had related donors and 4 patients had unrelated donors including one haploidentical transplantation. Best response before allo-SCT was RP in 8 patients and RC in 4 patients. Allo-SCT improved response in only 2 patients. Six patients had received therapy for HL progression/relapse post allo-SCT, including donor lymphocyte infusions (n=4). Median number of injection of nivolumab was 4 (range 1-10). Acute GVHD occurred in 2 patients after 1 injection (grade III skin acute GVHD) and 2 injections (grade IV skin acute GVHD) of nivolumab. In one patient, GVHD responded quickly to corticosteroids therapy. The patient who received haplo-identical allo-SCT presented with corticosteroid-refractory grade IV skin GVHD reversed after several extracorporeal photopheresis sessions. Both patients had prior history of grade II acute GVHD in the three months before nivolumab administration and treatment was stopped. Nivolumab did not modify chimerism. The only serious hematological adverse events were grade 4 neutropenia (1 patient) and grade 3 thrombocytopenia (1 patient). No other non-hematological adverse event was observed except a grade 2 cerebellar ataxia. With a median follow-up of 60 days post nivolumab initiation, 1 patient discontinued due to progressive disease, 2 patients due to acute GVHD and 9 patients remain on nivolumab. In our preliminary analysis of efficacy, 7 out of the 8 (87.5%) patients evaluable for response had clinical benefit, with 4 achieving partial response and 3 in complete response according to Cheson 2007 criteria. Of note, one of the patient developing acute GVHD post nivolumab achieved partial response. No data for the other patient presenting with acute GVHD after treatment was available at the time of analysis. CONCLUSIONS: Our preliminary results suggest that nivolumab is effective with manageable toxicity in patients with relapsed or refractory Hodgkin's lymphoma after allo-SCT. These encouraging results emphasize the need to delineate indications and perform prospective protocols. Disclosures Morschhauser: Genentech Inc./Roche: Other: Advisory boards.