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Risk-stratified treatment strategies have the potential to increase survival and lower toxicity in relapsed/refractory classical Hodgkin lymphoma (R/R cHL) patients. This study investigated the prognostic value of serum (s)TARC, vitamin D and lactate dehydrogenase (LDH), TARC immunohistochemistry and quantitative PET parameters in 65 R/R cHL patients who were treated with brentuximab vedotin (BV) and DHAP followed by autologous stem-cell transplantation (ASCT) within the Transplant BRaVE study (NCT02280993). At a median follow-up of 40 months, the 3-year progression free survival (PFS) was 77% (95% CI: 67–88%) and the overall survival was 95% (90–100%). Significant adverse prognostic markers for progression were weak/negative TARC staining of Hodgkin Reed-Sternberg cells in the baseline biopsy, and a high standard uptake value (SUV)mean or SUVpeak on the baseline PET scan. After one cycle of BV-DHAP, sTARC levels were strongly associated with the risk of progression using a cutoff of 500 pg/ml. On the pre-ASCT PET scan, SUVpeak was highly prognostic for progression post-ASCT. Vitamin D, LDH and metabolic tumor volume had low prognostic value. In conclusion, we established the prognostic impact of sTARC, TARC staining, and quantitative PET parameters for R/R cHL, allowing the use of these parameters in prospective risk-stratified clinical trials. Trial registration: NCT02280993.

Touchant préférentiellement les jeunes adultes, le lymphome de Hodgkin (LH) classique est une hémopathie maligne dont le traitement par chimiothérapie plus ou moins radiothérapie engendre de bons taux de guérison (> 80 %) avec cependant une toxicité à long terme significative. Certains cas sont réfractaires à la chimiothérapie ou rechutent précocement et nécessitent des chimiothérapies intensives aux lourds effets secondaires. L’étude de la physiopathologie des LH révèle que d’importantes altérations des interactions entre les cellules de Reed-Sternberg et leur micro-environnement impliquent la voie de signalisation Programmed Cell Death 1(PD-1)/PD-Ligand-1. Récemment, les anticorps anti-PD-1 ont montré des résultats spectaculaires dans les LH réfractaires ou en rechute avec une toxicité modérée, mais leur efficacité à long terme n’est pas encore établie. La place de ces traitements dans la stratégie globale de prise en charge des LH reste à déterminer.

•Brentuximab-vedotin in combination with bendamustine is highly active salvage therapy in R/R PTCL with an ORR of 68% and CR of 49%.•Patients who underwent an allo-stem cell transplantation in CR had better outcome. m-PFS and OS was 19.3 months and not reached.

•The REALYSA cohort is a source of RWD of high quality for lymphoma thanks to a multistep rigorous data validation process.•Effectiveness results on patients with first-line DLBCL seem consistent with literature and recent CTs.

The first-in-class small molecule inhibitor OTX015 (MK-8628) specifically binds to bromodomain motifs BRD2, BRD3, and BRD4 of bromodomain and extraterminal (BET) proteins, inhibiting them from binding to acetylated histones, which occurs preferentially at super-enhancer regions that control oncogene expression. OTX015 is active in haematological preclinical entities including leukaemia, lymphoma, and myeloma. We aimed to establish the recommended dose of OTX015 in patients with haematological malignancies. We report the results from a cohort of patients with lymphoma or multiple myeloma (non-leukaemia cohort).

The risk of central nervous system (CNS) dissemination in mantle cell lymphoma (MCL) is low and occurs late in the course of the disease. However, prognosis in such cases remains extremely poor despite high-dose antimetabolite chemotherapy. Among novel drugs used to treat relapsing MCL patients, ibrutinib, an oral inhibitor of Bruton tyrosine kinase, shows great promise. Here we report the clinical observation of 3 MCL patients with symptomatic CNS relapse treated with single-agent ibrutinib. All 3 patients had dramatic and rapid responses with almost immediate recovery from symptoms. We also confirmed that ibrutinib crosses the blood-brain barrier with parallel pharmacokinetic analyses in plasma and cerebrospinal fluid using a validated LC-MS/MS method. All responses were ongoing after 2 months to 1 year of follow-up.

The risk of central nervous system (CNS) dissemination in mantle cell lymphoma (MCL) is low and occurs late in the course of the disease. However, prognosis in such cases remains extremely poor despite high-dose antimetabolite chemotherapy. Among novel drugs used to treat relapsing MCL patients, ibrutinib, an oral inhibitor of Bruton tyrosine kinase, shows great promise. Here we report the clinical observation of 3 MCL patients with symptomatic CNS relapse treated with single-agent ibrutinib. All 3 patients had dramatic and rapid responses with almost immediate recovery from symptoms. We also confirmed that ibrutinib crosses the blood-brain barrier with parallel pharmacokinetic analyses in plasma and cerebrospinal fluid using a validated LC-MS/MS method. All responses were ongoing after 2 months to 1 year of follow-up.

Romidepsin is a histone deacetylase inhibitor approved in the USA for patients with recurrent or refractory peripheral T-cell lymphoma and has shown activity in this setting with mainly haematological and gastrointestinal toxicity. Although it has limited efficacy, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy is widely used for treatment of de-novo peripheral T-cell lymphoma. We aimed to assess the safety, tolerability, and activity of romidepsin combined with CHOP in patients with previously untreated disease.

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.

Lazarovici: Mundipharma: Other: Travel grant. Bouabdallah: Takeda: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Sandoz: Consultancy, Honoraria; Abbvie: Honoraria; Kite/Gilead: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses. Morschhauser: Roche: Consultancy, Speakers Bureau; Chugai: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Genmab: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: 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; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Laribi: Takeda: Other: Personal Fees, Research Funding; Novartis: Other: Personal Fees, Research Funding; AbbVie: Other: Personal Fees, Research Funding; BeiGene: Other: Personal Fees; Le Mans Hospital: Research Funding; IQONE: Other: Personal Fees; Astellas Phama, Inc.: Other: Personal Fees; AstraZeneca: Other: Personal Fees; Jansen: Research Funding. Feugier: Abbvie: Consultancy, Honoraria; Amgen: Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Astrazeneca: Consultancy, Honoraria. Sibon: iQone: Consultancy; Takeda: Consultancy; Abbvie: Consultancy; Roche: Consultancy; Janssen: Consultancy. Ribrag: Gilead: Membership on an entity's Board of Directors or advisory committees; PharmaMar: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Nanostring: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Argen-X: Research Funding; MSD Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Epizyme: Honoraria, Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Astex Pharmaceuticals: Research Funding; GSK: Research Funding; Infinity Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.Nivolumab. Presently labelled for relapse and refractory classical Hodgkin lymphoma and other malignancies

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.Brentuximab Vedotin and Bendamustine

Herbaux: Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Gilead Sciences, Inc.: Consultancy, Honoraria. Laribi:Roche: Other: Grant; Teva: Other: Grant; Hospira: Other: Grant; Sandoz: Other: Grant; Gilead: Other: Personal fees; Novartis: Other: Grant and personal fees; Takeda: Other: Grant and personal fees; Amgen: Other: Personal fees. Feugier:Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Guieze:abbvie: Honoraria; janssen: Honoraria; gilead: Honoraria.

Introduction.The BCL-2 inhibitor venetoclax has demonstrated high efficiency in relapsed/refractory (R/R) CLL patients with an overall response rate (ORR) of 79%, regardless of the TP53gene status. Venetoclax has then been EMEA-approved for CLL patients with TP53disruption who are unsuitable for or have failed a BCR inhibitor (BCRi) and those without TP53 inactivation who have failed both immunochemotherapy and a BCRi. Whether this agent provides a well-balanced safety/efficacy profile and a prolonged survival in real-world practice remains to be investigated.

Brice: Takeda Pharmaceuticals International Co.: Honoraria, Research Funding; Seattle Genetics: Research Funding; Roche: Honoraria; Gilead: Honoraria; Bristol Myers-Squibb: Honoraria. Thieblemont:Roche: Research Funding; Celgene: 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; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Background. L-asparaginase (L-ASPA) based-chemotherapy (chemo) is one of the most efficient treatment for patients with extra-nodal NK/T nasal type lymphoma, in front- line or at relapse. This treatment is combined either with radiation therapy (RT) if localized or with high dose therapy plus autologous stem cell transplantation (HDT/ASCT) if disseminated. However it may be associated with toxicities that may impair efficacy and survival.

Fenaux: AMGEN: Honoraria, Research Funding; CELGENE: Honoraria, Research Funding; NOVARTIS: Honoraria, Research Funding; JANSSEN: Honoraria, Research Funding.

Off Label Use: In this study, Yttrium-90 Ibritumomab Tiuxetan is administred in monotherapy for follicular lymphoma (MA) and in monotherapy or combination with intensive chemotherapy with autologous or allogeneic hematopoietic stem cell transplantation for CD20+ B-type lymphoma..

Background: The development of MDS or AML after treatment of lymphoma (Ly) by chemotherapy (CT), especially alkylating agents, topoisomerase II inhibitors (topo II inh), purine analogs, and autologous hematopoietic cell transplantation (auto ASCT) is well known. Those MDS/AML generally occur 3 to 7 years after CT, although often earlier (1 to 3 years) after topo II inh. Only occasional cases of MDS/AML have been described concomitantly or just after treatment of Ly, questioning their relationship with the underlying Ly. We investigated this occurrence in 2 French centers over a 6-year period.

In July 2004 in Europe, radioimmunotherapy (RIT) with Yttrium-90 Ibritumomab Tiuxetan ((90)Y-IT) obtained marketing authorization (MA) for follicular lymphoma (FL) in consolidation treatment in front line or relapse after rituximab treatment. Additional results also showed the potential interest of high-dose ((90)Y-IT) in monotherapy or in combination with intensive chemotherapy with autologous or allogeneic hematopoietic stem cell transplantation. Due to its particular toxicity profile (extended cytopenia and high rate of oral mucositis), the use of RIT in unselected patients is still debated. The aim of this retrospective cohort study was to evaluate the toxicity and efficacy of (90)Y-IT) in unselected consecutive adult patients treated for CD20+ B-type lymphoma.

Off Label Use: Romidepsin in association with CHOP for first line treatment of peripheral T-cell lymphoma. Morschhauser:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Tilly:Celgene: Research Funding. Coiffier:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Thieblemont: Oncoethix SA: Research Funding. Stathis:Oncoethix SA: Research Funding. Inghirami:Oncoethix SA: Research Funding. Karlin:Oncoethix SA: Research Funding. Morschhauser:Oncoethix SA: Research Funding. Gleeson:Oncoethix SA: Research Funding. Broussais:Oncoethix SA: Research Funding. Amorim:Oncoethix SA: Research Funding. Salles:Oncoethix SA: Research Funding. Facon:Oncoethix SA: Research Funding. Cunningham:Oncoethix SA: Research Funding. Vey:Oncoethix SA: Research Funding. Bourdel:Oncoethix SA: Employee of study CRO Other. Herait:Oncoethix SA: CMO and Shareholder Other. Zucca:Oncoethix SA: Research Funding.

Amorim: Oncoethix SA: Research Funding. Brice:Seattle Genetics, Inc.: Research Funding; Takeda Pharmaceuticals International Co.: Honoraria, Research Funding; Roche: Honoraria. Thieblemont:Oncoethix SA: Research Funding.

Rationale: BET-bromodomain (BRD) proteins are DNA readers that bind acetylated histone (H) tails preferentially at hyperacetylated superenhancer promoter regions and trigger gene transcription. The expression of several oncogenes, including c-MYC, is epigenetically regulated by BRD. OTX015 is a BRD 2, 3 and 4 inhibitor that prevents BRD binding to acetylated H4 and downregulates gene expression of BRD-dependent genes. OTX015 has been shown to inhibit the growth of diffuse large B-cell lymphoma (DLBCL) cells in vitroand in animal models.

Introduction. Risk of CNS dissemination in mantle cell lymphoma (MCL) is a rare and secondary event that occurs during the course of the disease. Prognosis from time of CNS involvement diagnosis is poor despite high-dose metabolite chemotherapy. New drugs are emerging in MCL treatment. The oral inhibitor of Bruton’s tyrosine kinase (BTK), Ibrutinib (Pharmacylics, Sunnyvale, CA), has demonstrated unprecedented single agent overall response rate in relapsed or refractory MCL. Efficacy of Ibrutinib in CNS relapse is not known.

Background:Romidepsin is a histone deacetylase inhibitor approved by the FDA for patients with cutaneous T-cell lymphoma and PTCL who have received at least 1 prior therapy. In recurrent/refractory PTCL, it has been evaluated as a single agent in 2 phase II studies with overall response rates of 25-38%(Piekarz, Blood2011 & Coiffier, J Clin Oncol2012). Toxicity is mainly hematologic and digestive. We here present the final analysis of a phase Ib/II trial aiming to evaluate the safety, tolerability and efficacy of romidepsin in association with CHOP in patients with previously untreated PTCL.