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Despite a moderate prevalence in low-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), thrombocytopenia remains a risk of severe bleeding and therapeutic options are still limited. There are only a few studies with eltrombopag (ELT), a thrombopoietin receptor agonist, in those patients. In this retrospective multicentre study, ELT was used in 50 patients with MDS and 11 with CMML, with no excess of marrow blasts and platelet counts of

The risk of venous thromboembolism (VTE) is higher in myeloma patients receiving immunomodulatory compounds. A VTE prophylaxis using low-molecular-weight heparin or aspirin is therefore proposed. Apixaban is an oral direct anti-Xa. Several studies have shown the efficacy and safety of apixaban in VTE prophylaxis compared to enoxaparin. The objective of this prospective phase 2 pilot study was to assess the risk of VTE and bleeding in patients with myeloma treated with immunomodulatory compounds lenalidomide (len) or thalidomide (thal), using apixaban in a preventive scheme. Myeloma patients requiring Melphalan-Prednisone-Thalidomide in the first line, or Lenalidomide-Dexamethasone in the relapse setting received apixaban, 2.5 mg x 2/day for 6 months. Venous (pulmonary embolism-PE, or symptomatic proximal or distal deep vein thrombosis-DVT, or all proximal asymptomatic events detected by systematic proximal bilateral compression ultrasound) or arterial thrombotic events, and bleeding events (ISTH 2005) were registered. One hundred and four patients were enrolled (mean age 69.8 ± 7.8 years), 11 in first line and 93 in relapse. Two venous thrombotic events were observed, for example, an asymptomatic proximal DVT and a symptomatic distal DVT, in the context of apixaban stopped 14 days before, due to lenalidomide-induced thrombocytopenia. No PE or arterial cardiovascular events were reported. Only one major and 11 CRNM hemorrhages were reported. These data must now be confirmed on a randomized large study.

Background: Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is a rare form of T-cell lymphoma arising adjacent to a breast implant, recently recognized as a provisional entity in the 2017 revised World Health Organization (WHO) lymphoma classification. The pathogenesis of this entity remains elusive even if gene alterations in epigenetic modifiers and JAK-STAT signaling are frequent. ECHELON 2 trial (Horwitz S et al. The Lancet 2019) has set BV-CHP as a new standard of treatment for CD30-positive peripheral T-cell lymphoma, mainly in systemic ALCL patients (pts) but not in BIA-ALCL. Our objective is to describe a series of pts with BIA-ALCL included in the LYSA registry focusing on the use of BV CHP as front-line chemotherapy for patient requiring chemotherapy. Methods: since 2016, a national multidisciplinary meeting has been implemented by the French Cancer Agency to better define therapeutic strategies for newly diagnosed cases after histologic confirmation. Meanwhile, BIA-ALCL registry was funded by the LYSA to collect ambispectively, in France and more recently in Belgium, patient clinical data including reasons for breast implantation, implant manufacturer, treatment and outcome. Results: from 2009 to 2021 , 85 pts (73 in France and 12 in Belgium) gave their informed consent to participate to the registry. Median age was 57 years (range 29-82) at diagnosis. In 39 out of 85 pts (45.9%) the first implant followed a mastectomy for breast cancer. In this analysis, only implants in the breast(s) where the lymphoma occurred have been considered. Five pts (5.9%) had bilateral lymphoma and 80 pts had unilateral lymphoma (35 left side and 45 right side), 35 pts were implanted once (41.2%), 35 twice (41.2%) and 15 pts (17.6%) 3 times or more. The median period between first implant and BIA-ALCL diagnosis was 12.2 years (range 4.1-40.5), and 7 years (range 0.2-25.4) from last implant to diagnosis. The clinical presentation was seroma in 64 pts (75.3%), breast tumor mass with or without seroma in 18 pts (21.1%) and 3 pts were diagnosed without any mass or seroma (1 contiguous lymph node involvement, 2 in the context of systematic implant removal). The two main clinical presentation (i.e. seroma and tumor mass) were most often correlated with the two distinct histological subtypes (in "situ/mixed" (n=62) or "infiltrative" (n=21)). For 2 pts, histological subtype was not available. The majority of pts were Ann Arbor stage I-II (n=65, 76.5%), and 18 (21.2%) pts were stage IV. Stage was unknown in 2 pts. Considering available information, almost all patients had at least one silicone-filled (n=76) and at least one textured implant (n=85) with Biocell texturation (n=61, 71.8%). No patient had only smooth implant. Implant removal with total capsulectomy was performed in 66 patients and 25 underwent chemotherapy based on CHOP or CHOP-like (4 to 6 cycles) chemotherapy regimens (n=13), BV-CHP (6 cycles) (n=10) and others (n=2). Among the patients receiving chemotherapy, CR was obtained in 21 pts (84%) and in 2 pts failed to respond (8%). Among the patients treated with BV-CHP, 8 pts achieved CR (80%) and 2 pts were not yet evaluated at the time of analysis. No limiting toxicity was noted. After a median follow-up of 28.6 months, 78 pts are alive and free of evolutive disease and 8 are lost to follow up. Seven pts died, either from lymphoma progression alone (n=2) or associated with concomitant active breast cancer (n=2), one from breast cancer alone, one from lung epidermoid cancer and one due to myocardial infarction. Patients with an "infiltrative" histological subtype have a significantly worse outcome with a 2y-PFS of 73.8% vs 96.7% for other subtypes ("in situ/mixed subtypes") (p=0.0039, HR=5.3) and a 2y-OS of 78.7% vs 100% (p=0.0022, HR=8.5). With a median follow-up of one year, the 10 patients treated with BV-CHP are alive and free of evolutive disease at the time of analysis. Conclusions: We report on the basis of a limited series of patients that 6 cycles of BV-CHP provide an excellent disease control in patients with BIA-ALCL requiring chemotherapy. Confirmation of these results on a larger series of patients with a longer follow-up is needed. Such observation provides basis for a prospective trial in order to determine if treatment with BV-CHP could be installed as a standard of care for higher risk patients with BIA-ALCL, as those presenting with tumor mass and /or infiltrative subtype. Disclosures Le Bras: Novartis: Honoraria; Celgene BMS: Research Funding; Takeda: Honoraria, Research Funding; Kite Gilead: Honoraria. Bachy: Kite, a Gilead Company: Honoraria; Novartis: Honoraria; Daiishi: Research Funding; Roche: Consultancy; Takeda: Consultancy; Incyte: Consultancy. Bonnet: Roche: Consultancy. André: AbbVie: Other: Travel/accomodation/expenses; Roche: Other: Travel/accomodation/expenses, Research Funding; Johnson & Johnson: Research Funding; Celgene: Other: Travel/accomodation/expenses; Bristol-Myers-Squibb: Consultancy, Other: Travel/Accommodations/Expenses; Karyopharm: Consultancy; Gilead: Consultancy, Other: Travel/Accommodations/Expenses; Incyte: Consultancy; Takeda: Consultancy, Research Funding. Haioun: Amgen: Honoraria, Research Funding; Servier: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Miltenyi: Honoraria, Research Funding.

Background In contrast to the high cure rates in young patients (pts) treated with anthracycline-based chemotherapy, classical Hodgkin lymphoma (cHL) prognosis is poor in elderly pts, and very few data exist for pts considered too frail to receive standard-dose chemotherapy. In those patients, limited therapeutic options are available. Among the new immune-oncology drugs, Nivolumab, an anti-PD1 antibody, has demonstrated high response rate and very good tolerance, and is now approved in relapse and refractory (R/R) cHL. However, data on its use in the frontline setting are scarce. Material and methods We designed a prospective, open-label, multi-centric phase II study, to assess the efficacy and safety of nivolumab alone, or in combination with vinblastine in naive pts aged 61 years and older, with cHL and coexisting medical conditions. Pts were eligible if they had a Cumulative Illness Rating Scale-Geriatric (CIRS-G) score of 6 or more. Treatment consisted in an induction phase of 6 nivolumab injections, delivered at a flat dose of 240 mg every 14 days. Early assessment was done at 12 weeks by PET-CT and CT-scan. Pts who achieved complete metabolic response (CMR) at early assessment completed treatment with nivolumab monotherapy for 18 additional cycles (consolidation phase). Pts who obtained partial metabolic response (PMR) or non metabolic response (NMR, stable disease) received a combination of 18 cycles of nivolumab plus vinblastine, administered intravenously. The primary objective of the study was to assess the CMR rate based on central review at the end of treatment (EOT). Results From August 30th, 2018 to April 28 th, 2020, 64 pts were included in 31 centers, which composed the full analysis set (FAS), used for safety evaluation. Among these 64 pts, 56 pts were fully evaluable and constituted the efficacy set (ES) used for the efficacy analysis (8 pts progressed early or were not assessed by PET-CT). The median age at inclusion in the ES was 75 years [range: 62-91]. Patients had a median CIRS-G score of 10 [range: 6-18] at baseline, and a median G8 score of 12.5 [range: 6-17]. Seventy-three percent of pts had a stage III-IV disease and 42.9% of pts had B symptoms. At EOT, 16 pts (28.6%) achieved CMR according to central PET-CT review. Ten pts (17.9%) achieved PMR, 10 pts were in NMR (17.9%) and progressive metabolic disease was observed in 17 pts (30.4%). Three pts were not evaluated. The overall response rate at end of induction was 51.9%, (9 CMR and 18 PMR). 23 pts received a consolidation with nivolumab and vinblastine. With a median follow-up of 20.1 months, median PFS was 9.8 months [95% CI: 4.2;12]. 15/64 pts of the FAS died during treatment (23.4%): 6 pts from lymphoma, 2 pts from toxicity of study treatment and 2 pts from concurrent illness. One patient died from toxicity of additional treatment after progression, and 4 pts from other causes. The 2-year overall survival was 76.7% [95% CI: 59.6;87.3]. 49/64 pts (76.6%) experienced at least one AE, among which 32 pts experienced grade 3-4 AEs. The 3 more frequent grade 3-4 AEs were neutropenia (8 pts), sepsis (7 pts) and respiratory tract infection (5 pts). Adverse events were related to nivolumab in 36 pts and led to treatment discontinuation in 19 pts (29.7%). Adverse events of special interest i.e., immune-related AEs, were recorded in 22 pts, including 3 pneumonitis, 1 myocarditis, 1 encephalitis and 1 colitis. Among the 64 pts of the FAS, 34% of pts completed the treatment. The median number of cycles administered was 7 [range: 1-24] for nivolumab and 17 [range: 1-18] for vinblastine. Conclusion The NIVINIHO study is the first study to assess the efficacy and safety of an immune checkpoint inhibitor for first line therapy in elderly, frail patients with cHL. The results suggest that in this setting, a nivolumab-based therapy is active in a subset of pts. Further studies and biological analysis are planned to determine which patients may benefit from this approach. Figure 1 Figure 1. Disclosures 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. OffLabel Disclosure: Nivolumab. Presently labelled for relapse and refractory classical Hodgkin lymphoma and other malignancies

INTRODUCTION In BCR-ABL1-negative myeloproliferative neoplasms, myelofibrosis (MF) is either primary (PMF) or secondary (SMF) to polycythemia vera or essential thrombocythemia. MF is characterized by an increased risk of transformation to acute myeloid leukemia (AML) and a shortened life expectancy. METHODS Because natural histories of PMF and SMF are different, we studied by targeted next generation sequencing the differences in the molecular landscape of 86 PMF and 59 SMF and compared their prognosis impact. RESULTS PMF had more ASXL1 (47.7%) and SRSF2 (14%) gene mutations than SMF (respectively 27.1% and 3.4%, P = .04). Poorer survival was associated with RNA splicing mutations (especially SRSF2) and TP53 in PMF (P = .0003), and with ASXL1 and TP53 mutations in SMF (P

Lenalidomide (LEN) has been shown to yield red blood cell (RBC) transfusion independence in about 25% of lower risk myelodysplastic syndromes (MDS) without del(5q), but its efficacy in patients clearly refractory to erythropoiesis-stimulating agents (ESA) is not known. We report on 31 consecutive lower-risk non-del(5q) MDS patients with anaemia refractory to ESA and treated with LEN in a compassionate programme, 20 of whom also received an ESA. An erythroid response was obtained in 15 patients (48%), including 10 of the 27 (37%) previously transfusion-dependent (RBC-TD) patients, who became transfusion-independent (RBC-TI). Nine of the responders relapsed, whereas 6 (40%) were still responding and transfusion-free after 11(+)-31(+) months. Median response duration was 24 months. The erythroid response rate was lower in refractory cytopenia with multilineage dysplasia (27% vs. 60%) and tended to be higher in patients treated with LEN + ESA (55% vs. 36%). Response duration was significantly longer in responders who obtained RBC-TI and in patients treated with LEN after primary resistance to ESA. The main toxicity of LEN was cytopenias. We confirm that, in a patient population of lower risk MDS without del 5q clearly resistant to ESA, LEN is an interesting second line therapeutic option. Its combination with ESAs in this context warrants prospective studies.

Background: Myelofibrosis (MF) is the less frequent Philadelphia-negative myeloproliferative neoplasms (MPN). We have included in a nationwide database primary (P), post-polycythemia (PPV) and post-essential thrombocythemia (PET) MF diagnosed in France since 2005. Methods: Inclusion criteria were: diagnostic of MF after 2005; according strictly to WHO (bone marrow biopsy mandatory); informed consent. The registry was launched in Oct. 2013, and 26 hematology centers included patients (pts). Summary statistics were reported, namely median [Interquartile range, IQR] or percentage. Baseline characteristics were compared across IPSS groups using chi-square test or Mann and Whitney test. Kaplan-Meier survival curves were plotted and compared by the log-rank test. Results: At time of analysis (June 2016) a total of 527 pts were included in the registry, complete baseline data were available in 499 (95%), and follow-up (FU) data in 433 (87%). Median [IQR] age and M/F sex ratio were 71 [63-78] years and 315/184 (1.7), respectively (resp). 301 (60%) pts had PMF, 182 (36%) had secondary MF (including 64 PPVMF and 118 PETMF) and 16 had pre-fibrotic MF. Five percent of pts had a familial history of hematologic malignancy, and 22% a history of thrombosis or hemorrhage. Splenomegaly was present in 386 (77%) with a median [IQR] spleen size of 4 cm [1-8] below costal margin, and was symptomatic in 11% of pts. Constitutional symptoms were present in 107 (21%) (weight loss in 56, night sweats in 61, fever in 14), and ECOG score was 0, 1, 2, and 3 in 53%, 36%, 11% and 0.3% of pts, resp. Median [IQR] Hemoglobin, WBC and platelet counts were 109 g/L [94-122], 9.3 G/L [5.7-16.0] and 257 G/L [138-430], resp. Circulating blast cells were present in 41%, LDH was above normal value in 95% of pts, median EPO level was 54 [11 - 57] U/L. Grade of fibrosis (WHO) was 1, 2, and 3 in 2%, 66% and 32% of pts, resp. Karyotype was done in 321 pts, normal in 173 (54%), abnormal with favorable prognostic value in 89 (30%) and unfavorable in 30 (10%) (29 failures). A total of 461 (92%) pts had molecular testing: 60% were JAK2V617F positive, 4% had MPL and 7% had CALR mutations, and 99 (28%) over the 352 pts with triple testing were triple negative. IPSS risk categories were low, int-1, int-2 and high in 68 (14%), 168 (34%), 158 (32%), and 105 (21%) pts, resp. In addition to constitutional symptoms, there was a significant increase in the prevalence of clinical signs across IPSS categories (from low to high risk): symptomatic spleen (p=0.016) -though no difference in spleen size was found (p=0.18)-, early satiety (p=0.013), ECOG score (p= 0.0001), bone pain (p=0.002). Moreover, among biological parameters, there was an increase across IPSS groups in WBC (p=0.029), LDH (p=0.0007), ferritin (p=0.003), circulating CD34+ cells (p=0.020), EPO level (p=0.035). In contrast, a decrease was seen for hemoglobin and platelets (p=0.0001 for both). Lastly, frequency of grade 3 fibrosis increased with IPSS (p=0.043), while no evidence of difference was found regarding abnormal karyotype and mutational pattern. Median FU was 33 months [9-63 months]. Among those 433 pts with FU data, median FU was 38 months [19-68], and 124 (29 %) pts had died at the time of analysis, including 13%, 17%, 31%, and 40% of pts from the Low, Int-1, Int-2, and High risk groups, resp (p= 0.0001, figure 1). In the 450 pts with treatment data, treatments received during FU included cytoreductive drug (41%), Jak-inhibitors (35%), Interferon alpha (18%), IMIDs (4%). Splenectomy was performed in only 14 (3%) pts. Forty percent of pts received packed red blood cells, and 12% platelets transfusions. 49 (11%) patients participated in a clinical trial, and 27 (6%) were allografted. Conclusion: This is the first analysis of the French MF observatory after inclusion of more than 500 pts diagnosed and treated during the past 10 years. Complete baseline data and follow-up information available for the majority of pts should allow for new studies of outcomes and influence of clinical and biological parameters, as well as reassessment of prognostic models in the era of new targeted therapies. Figure 1 Comparison of overall survival according to IPPS Figure 1. Comparison of overall survival according to IPPS Figure 2 Figure 2. Disclosures Etienne: Pfizer: Speakers Bureau; BMS: Speakers Bureau; ARIAD: Speakers Bureau; novartis: Consultancy, Speakers Bureau. Tavitian:Novartis: Membership on an entity's Board of Directors or advisory committees. Ugo:Novartis: Membership on an entity's Board of Directors or advisory committees. Kiladjian:Novartis: Honoraria, Research Funding; AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding.