Anti-PD-1 therapy provides high response rates in Hodgkin lymphoma (HL) patients who have relapsed or are refractory (R/R) to autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV), but median progression free survival (PFS) is only one year. The efficacy of treatment following anti-PD-1 is not well known. We retrospectively investigated the efficacy of salvage therapies for unsatisfactory response to anti-PD-1 therapy, assessed by PET-CT according to the Lugano criteria, in 30 R/R HL patients. Patients were highly pre-treated before anti-PD-1 (70% received ASCT and 93% BV). Unsatisfactory responses to anti-PD1 therapy were progressive disease (PD) (n=24) and partial response (PR) (n=6). For the 24 PD patients, median anti-PD-1 related PFS was 7.5 months (95%CI, 5.7-11.6); 17 received subsequent CT alone (Group 1) and 7 received CT in addition to anti-PD-1 (Group 2). 16/24 patients (67%) obtained an objective response. In the 15 patients treated with the same CT, twelve obtained PR or complete response (CR). In Group 1, there were 7 CR (41%), 3 PR (18%), and 7 PD (41%). In Group 2, there were 4 CR (57%), 2 PR (29%), and 1 SD (14%). No unexpected toxicity was observed. Six patients who achieved response proceeded to allogeneic SCT. With a median follow-up of 12.1 months (7-14.7), the median PFS following the initiation of CT was 11 months (95%CI, 6.3; not reached) and the median of overall survival was not reached. These observations in highly pre-treated HL patients suggest that anti-PD-1 therapy might re-sensitize tumor cells to CT. This article is protected by copyright. All rights reserved.

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Abbreviations: aaIPI = Age-adjusted International Prognostic Index; DLBCL = diffuse large-B-cell lymphoma; LVEF = left ventricular ejection fraction; MCL = mantle-cell lymphoma; R-DHAP = rituximab-dexamethasone aracytine carboplatine; TCLO = transfert lung factor for CO. a Only for patients with DLBCL.Bone Marrow Transplantation (2016) 51, 319-321

Patients with relapsed or refractory Hodgkin lymphoma (RR-HL) have poor outcomes. Brentuximab vedotin (BV), an antibody-drug conjugate comprising an anti-CD30 antibody conjugated to the potent anti-microtubule agent, monomethyl auristatin E, induces high tumour responses with moderate adverse effects. In a retrospective study, we describe objective response rates and subsequent allogeneic stem cell transplantation (allo-SCT) in patients with RR-HL treated by BV in a named patient program in two French institutions. Twenty-four adult patients with histologically proven CD30(+) RR-HL treated with BV were included from July 2009 to November 2012. Response to BV treatment was evaluated after four cycles. Eleven patients were in complete response (45.8%), while five patients were in partial response (20.8%), with an overall response rate of 66.6%. Eight patients failed to respond to BV (33.3%). All of the responding patients could receive consolidation treatment after BV: three patients underwent autologous stem cell transplantation (auto-SCT), three patients received a tandem auto-SCT/allo-SCT, nine patients received allo-SCT and one patient was treated with donor lymphocyte infusion. We found no treatment-related mortality at day 100 among the 12 patients who underwent BV following by allogeneic transplantation. With a median follow-up of 20 months (range 10.5-43.2), none of them relapsed or died. BV followed by allo-SCT represents an effective salvage regimen in patients with RR-HL.

The transcription factor PLZF (promyelocytic leukemia zinc finger protein) acts as an epigenetic regulator balancing self-renewal and differentiation of hematopoietic cells through binding to various chromatin-modifying factors. First described as a transcriptional repressor, PLZF is also associated with active transcription, although the molecular bases underlying the differences are unknown. Here, we reveal that in a hematopoietic cell line, PLZF is predominantly associated with transcribed genes. Additionally, we identify a new association between PLZF and the histone methyltransferase, EZH2 at the genomic level. We find that co-occupancy of PLZF and EZH2 on chromatin at PLZF target genes is not associated with SUZ12 or trimethylated lysine 27 of histone H3 (H3K27me3) but with the active histone mark H3K4me3 and active transcription. Removal of EZH2 leads to an increase of PLZF binding and increased gene expression. Our results suggest a new role of EZH2 in restricting PLZF positive transcriptional activity independently of its canonical PRC2 activity.

Carmustine shortage has led to an increase use of alternative conditioning regimens prior to autologous stem cell transplantation for the treatment of lymphoma, including Bendamustine-based (BeEAM). The aim of this study was to evaluate the safety of the BeEAM regimen in a large cohort of patients. A total of 474 patients with a median age of 56 years were analyzed. The majority of patients had diffuse large B-cell lymphoma (43.5%). Bendamustine was administered at a median dose of 197 mg/m /day (50-250) on days-7 and -6. The observed grade 1-4 toxicities included mucositis (83.5%), gastroenteritis (53%), skin toxicity (34%), colitis (29%), liver toxicity (19%), pneumonitis (5%), and cardiac rhythm disorders (4%). Nonrelapse mortality (NRM) was reported in 3.3% of patients. Acute renal failure (ARF) was reported in 132 cases (27.9%) (G ≥2; 12.3%). Organ toxicities and death were more frequent in patients with post conditioning renal failure. In a multivariate analysis, pretransplant chronic renal failure, bendamustine dose >160 mg/m and age were independent prognostic factors for ARF. Pretransplant chronic renal failure, hyperhydration volume, duration of hyperhydration, and etoposide dose were predictive factors of NRM. A simple, four-point scoring system can stratify patients by levels of risk for ARF and may allow for a reduction in the bendamustine dose to avoid toxicity. Drugs shortage may have dangerous consequences. Prospective, comparative studies are needed to confirm the toxicity/efficacy extents from this conditioning regimen compared to other types of high dose therapy.

BackgroundThe contribution of patients’ non-medical characteristics to individual physicians’ decision-making has attracted considerable attention, but little information is available on this topic in the context of collective decision-making. Medical decision-making at cancer centres is currently carried out using a collective approach, at MultiDisciplinary Team (MDT) meetings. The aim of this study was to determine how patients’ non-medical characteristics are presented at MDT meetings and how this information may affect the team’s final medical decisions.DesignObservations were conducted at a French Cancer Centre during MDT meetings at which non-standard cases involving some uncertainty were discussed from March to May 2014. Physicians’ verbal statements and predefined contextual parameters were collected with a non-participant observational approach. Non numerical data collected in the form of open notes were then coded for quantitative analysis. Univariate and multivariate statistical analyses were performed.ResultsIn the final sample of patients’ records included and discussed (N = 290), non-medical characteristics were mentioned in 32.8% (n = 95) of the cases. These characteristics corresponded to demographics in 22.8% (n = 66) of the cases, psychological data in 11.7% (n = 34), and relational data in 6.2% (n = 18). The patient’s age and his/her “likeability” were the most frequently mentioned characteristics. In 17.9% of the cases discussed, the final decision was deferred: this outcome was positively associated with the patients’ non-medical characteristics and with uncertainty about the outcome of the therapeutic options available.LimitationsThe design of the study made it difficult to draw definite cause-and-effect conclusions.ConclusionThe Social Representations approach suggests that patients’ non-medical characteristics constitute a kind of tacit professional knowledge that may be frequently mobilised in physicians’ everyday professional practice. The links observed between patients’ attributes and the medical decisions made at these meetings show that these attributes should be taken into account in order to understand how medical decisions are reached in difficult situations of this kind.

Lenalidomide is an oral non-chemotherapy immunomodulatory agent with an acceptable toxicity profile and manageable side-effects. Efficacy has widely been demonstrated, especially in MCL, FL and non-Germinal Center DLBCL patients. Further studies are now warranted to better define the strategy for the use of lenalidomide in B-NHL patients, and clarify which subgroup of patients will really benefit of lenalidomide as part of first-line treatment or in a relapsed/refractory setting.