Abstract: The previous studies assessing the relationship of cytogenetic abnormalities to JAK2 status have not shown any significant associations, although numbers have generally been too small to make a definitive comment. We therefore assessed the JAK2 V617F mutation status of 337 patients from 39 centers (175 males, 161 females; median age at time of study 71 years old, range 32–98). Patients were classified as follows: 100 with typical MDS, 10 with 5q- syndrome, 17 with AREB-2, 2 with RARS, 13 with RARS-T, 23 with MPD/MDS, 12 with CMML, 142 with typical MPDs, 5 with hypereosinophilic syndrome (HES), 7 with AML with multi-lineage dysplasia from Ph- MPD, 10 with aCML Ph- or MPD/MDS-u and 25 with typical CML Ph+. Bone marrow or blood derived genomic DNA was screened for the JAK2 mutation. The JAK2 V617F mutation was found in 109/337 pts (32%): typical MPD-Ph− (47%) cases, MDS (4.5%), 5q- syndrome (60%), AREB-2 (64%), CMML (42%), MDS/MPD (36%). A clonal cytogenetic abnormality was detected by R-banding in 159/337 cases (47%). The JAK2 mutation was associated with a chromosomal abnormality in 81/159 cases (51%). The most common chromosome abnormality associated with JAK2 mutation was the gain of chromosome 9 (n= 22, Associated with JAK2 mutation: 19/22 cases 86%). The second most common abnormality was partial deletion of 20q (n=30, Associated with JAK2 mutation: 19/30 cases 63%). The partial or complete loss of chromosome 7 (n=16, Associated with JAK2 mutation: 6/11), deletion of 5q- (n=10, Associated with JAK2 mutation: 6/10), gain of chromosome 8 (n=11, Associated with JAK2 mutation: 7/11), partial deletion of 11q (n=8, Associated with JAK2 mutation: 5/8), partial deletion of 12p (n=6 Associated with JAK2 mutation 4/6), partial deletion of 13q (n=5, Associated with JAK2 mutation: 4/5). Patients with trisomy 9 and JAK2 mutation were classified as follows : polycytemia vera (PV) n=4 (100% JAK2 mutated), essential thrombocytemia (ET) n=3 (100% JAK2 mutated), idiopathic myelofibrosis (IMF), n=2 (100% JAK2 mutated), MPD/MDS, n=3 (67% JAK2 mutated), secondary AML post MDS, n=1 (JAK2 mutated), atypical MPD, n=6 (100% JAK2 mutated), MMCL, n=1(JAK2 mutated). The V617 mutation was not found in the case of de novo AML, and 2 typical MDS cases. 9 males, 10 females, the median age: 68 years old, range 40–98 years old, median white cell count (WCC) 11 G/l, range 2.4–50.7 G/l (13/19 pts & gt; 10G/l), median hemoglobin 13.5 g/dl, range 9–20.2 g/dl (5/19 pts & gt; 17g/dl), median platelet count 667G/l range 9–1769 G/l (9/19 pts & gt; 500 G/l). The BCR/ABL transcript (multiplex PCR) was not detected in all of these cases. In this study the gain of chromosome 9 associated with JAK2 V617F mutation was the most frequent chromosome abnormality (100%) observed in typical MPDs and atypical syndrome such as MDS/MPD. In summary, previous studies assessing the relationship of cytogenetic abnormalies to JAK2 status did not show any significant association (ref). The del(20q), del(13q), trisomy 8 and del(5q) are known to be recurring non-specific cytogenetic abnormalities, and some of them are also detectable in patients with JAK2 mutation positive or negative. We describe here a significant association the JAK2 V617F mutation and trisomy of chromosome 9 that was detected in a cohort of patients with gain of chromosome 9. Clearly, in addition to PV, IMF, and ET these associations were found in other disease entities, high frequency in the case of atypical MPDs particularly in the case of aCML. Previously, Campbell et al. reported 10 patients with a trisomy 9, in typical MPDs, all of them were V617F+. A longer follow-up and morphological diagnosis is however necessary to determine the prognostic signification of JAK2 mutation and +9 in the cases of classic myeloproliferative syndromes and atypical syndrome such as MDS/MPD overlap syndrome.

Abstract: Orbital NHL (ocular and/or adnexal involvement) represents less than 1% of all lymphomas but about half of malignant tumors of the eye and/or ocular adnexae. We therefore reviewed all patients treated at the Institut Curie between 1970 and 2003 for a NHL exhibiting initial orbital localization to define their initial characteristics, natural history and prognostic factors. Among 172 patients, 145 cases with completed datas were selected for the study. Pathological review according to the WHO classification showed 52 cases of MALT-type lymphoma (36%), 32 lymphoplasmocytic lymphomas (22%), 14 patients with lymphocytic lymphoma, 7 cases of follicular lymphoma, 13 unspecified low grade lymphomas [namely, 118 cases (82%) of low grade NHL], 22 patients with diffuse large B-cell lymphoma (15%), 2 cases of mantle cell lymphoma, 2 Burkitt’s lymphomas and one T-lymphoblastic lymphoma [namely, 27 cases (18%) of high-grade NHL] . Initial characteristics were: median age 66 years (range 3–96), sex ratio M/F 0.6, B symptoms 6%, PS≥2 in 4% of patients, stages III–IV 31.7%, bone marrow involvement 12%, elevated LDH in 18% and IPI 0-1/2/3/4-5 in 92/28/13 and 1 cases, respectively. Anatomic localizations were intra-orbital in 39 patients (27%), conjunctival in 38 (26%), eyelid in 9 cases, lachrymal in 8 and other in 8 cases. Treatment of selected patients consisted of abstention in 2 cases, surgical complete resection in 5 cases, mono or polychemotherapy alone (CT) in 4 cases, and radiotherapy alone in 98 cases (68%) or with CT in 36 cases (25%). With a median follow-up of 90 months (range 3–314), the 5-year relapse-free (RFS) and overall (OS) survivals were 64% and 79% for the low-grade NHL, and 43% and 50% for the high-grade NHL. Prognostic factors were determined for the 118 low-grade patients. In univariate analysis, age greater than 59 years, elevated IPI score and elevated LDH level were prognostic for lower RFS and OS. In multivariate analysis, age greater than 59 years was the only prognostic factor for both lower RFS and OS (Figure 1). In conclusion, with a median follow-up of 7.5 years, our large monocentric cohort of patients represents one of the most important series that defines the initial characteristics, natural history and prognostic factors of NHL with initial orbital localization. Figure Figure

Abstract: The overall response rate following 4 induction cycles of VTD prior to ASCT is higher than that of 4 cycles of VCD.

Abstract: High-dose melphalan (HDM) and transplantation are recommended for eligible patients with multiple myeloma. No other conditioning regimen has proven to be more effective and/or safer. We previously reported in a phase 2 study that bortezomib can safely and effectively be combined with HDM (Bor-HDM), with a 32% complete response (CR) rate after transplantation. These data supported a randomized phase 3 trial. Randomization was stratified according to risk and response to induction: 300 patients were enrolled, and 154 were allocated to the experimental arm (ie, arm A) with bortezomib (1 mg/m2 intravenously [IV]) on days −6, –3, +1, and +4 and melphalan (200 mg/m2 IV) on day –2. The control arm (ie, arm B) consisted of HDM alone (200 mg/m2 IV). There were no differences in stringent CR + CR rates at day 60 posttransplant (primary end point): 22.1% in arm A vs 20.5% in arm B (P = .844). There were also no differences in undetectable minimum residual disease rates: 41.3% vs 39.4% (P = .864). Median progression-free survival was 34.0 months for arm A vs 29.6 months for arm B (adjusted HR, 0.82; 95% CI, 0.61-1.13; P = .244). The estimated 3-year overall survival was 89.5% in both arms (hazard ratio, 1.28; 95% CI, 0.62-2.64; P = .374). Sixty-nine serious adverse events occurred in 18.7% of Bor-HDM–treated patients (vs 13.1% in HDM-treated patients). The proportion of grade 3/4 AEs was similar within the 2 groups (72.0% vs 73.1%), mainly (as expected) blood and gastrointestinal disorders; 4% of patients reported grade 3/4 or painful peripheral neuropathy in arm A (vs 1.5% in arm B). In this randomized phase 3 study, a conditioning regimen with Bor-HDM did not improve efficacy end points or outcomes compared with HDM alone. The original trial was registered at www.clinicaltrials.gov as #NCT02197221.

Abstract: Background EMMY is a large-scale epidemiological study to assess the epidemiology and real-life management of multiple myeloma (MM). Proteasome inhibitors (PI), immunomodulators (IMID) and anti-CD38, provide broad therapeutic solutions for the management of first-line Multiple Myeloma (MM). At more advanced stages, the therapeutic possibilities in patients already exposed to these 3 therapeutic classes are limited. The EMMY study allows to describe the characteristics and the real-life efficacy of treatments in tri-exposed patients. Methods EMMY is a descriptive, multicenter, national, non-interventional study conducted in 72 IFM (Intergroupe Francophone du Myélome, sponsor) centers in France. Any patient initiating treatment for MM over a 3-month observation period, from October to December, is included, since 2017. It is a dynamic cohort with the inclusion of 1000 additional patients each year (2765 patients included at the end of 2019). Data are updated annually from hospital records up to 2020. Patients with tri-exposure to the 3 classes IMID, IP and anti CD38 were identified, and the index date was defined as the initiation of the next line. The median time to next treatment (mTTNT), median progression-free survival (mPFS), and median overall survival (mOS) were estimated for these patients. Results are focused in patients refractory to the previous line (PL-Ref). Results After 3 years of data collection in EMMY, 491 patients (17.8%) were identified as tri-exposed in the cohort. The median age was 69.9 years [62.2-75.8] with 158 patients (32.2%) & lt; 65 years and 63 (12.8%) ≥ 80 years. When available, patients had ECOG 0 or 1 for 59.3% (n=211), high cytogenetic risk for 29.5% (RD) (n=65), an ISS of 1/2/3 for 25.3, 28.5 and 46.2% and at least one comorbidity for 32% (n=157). The patients were tri-exposed at the end of L2, L3, L4, L5 and L6+ for respectively 2%, 16.9%, 26.9%, 26.3% and 27% of them with a median time from diagnosis to the index date of 54.9 months (mo) [32.9 -89.7]. The proportion of patients early tri-exposed as of L3 or L4 increased over the years with respectively 9.8% (L3) and 15.7% (L4) in 2017 (n=51), 11% and 18.9% in 2018 (n=127), 17.1% and 26.8% in 2019 (n=164) and 24.5% and 37.4% in 2020 (n=147). Time from diagnosis to the index line decreased from 64.6 mo (2017) and 62.8 mo (2018) to 54.5 mo (2019) and 49.5 mo (2020). Half patients (52.5%) had previously received ASCT. At the index date, patients had previously been treated with bortezomib (98%), carfilzomib (21.2%), ixazomib (10.4%), lenalidomide (90.4%), thalidomide (35.8%), pomalidomide (61,9%), daratumumab (96.5%) and isatuximab (3.5%). In overall, 86% were refractory to anti-CD38, 51% refractory to 3 classes, and 31% to 2 classes. Of them, 89.2% (438) were refractory to the line prior to the index line (PL-Ref). The mPFS was 5,1 mo 95%CI [4.4 - 6.3] and the mTTNT 6.9 mo 95%CI [6.1 -8.2] for the whole cohort (n=481). In the 438 PL-Ref patients, mPFS was 4.8 mo 95%CI [4.1-6] and mTTNT was 6.6 mo 95%CI [5.5; 7.8] (Figure 1). The mOS was 17.7mo 95%CI [14.2 - 20.2] for the whole cohort with mOS of 16.6 mo 95%CI [13.1 - 19.8] in PL-Ref patients. Conclusion Advances in the management of myeloma are leading to the increasingly early use of combination treatments with IMID, PI and anti-CD38 antibodies in the treatment of multiple myeloma. As a result, patients are increasingly early exposed to these 3 major classes. The EMMY cohort confirms that patients are triple exposed to PIs, IMID, and anti CD38 at an increasingly early stage in the management of MM. Most of them were refractory to the last line and to anti-CD38 antibodies. The majority remains healthy with ECOG less than 2 and few comorbidities. Median PFS and TTNTs are approximately six months, lower than those observed with modern anti-BCMA immunotherapies. These results underline the importance of developing new therapeutic strategies in triple-exposed patients such as novel immunotherapy including bi-specific antibody/CART cells. Figure 1 Figure 1. Disclosures Perrot: Abbvie: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria, Research Funding; GSK: 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; BMS Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hulin: Janssen: Honoraria; abbvie: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; Celgene/BMS: Honoraria. Macro: takeda: Honoraria; abbvie: Honoraria; sanofi: Honoraria; celgene bms: Honoraria; janssen: Honoraria. Moreau: Abbvie: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Celgene BMS: Honoraria; Oncopeptides: Honoraria. Leleu: Roche: Honoraria; Pierre Fabre: Honoraria; Oncopeptides: Honoraria; Novartis: Honoraria; Mundipharma: Honoraria; Merck: Honoraria; Karyopharm Therapeutics: Honoraria; Janssen-Cilag: Honoraria; Gilead Sciences: Honoraria; Celgene: Honoraria; Carsgen Therapeutics Ltd: Honoraria; Bristol-Myers Squibb: Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Other: Non-financial support; Amgen: Honoraria; AbbVie: Honoraria. Manier: Novartis: Consultancy, Research Funding; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene - Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Karlin: Takeda: Honoraria, Other: member of advisory board; oncopeptide: Honoraria; Celgene-BMS: Honoraria, Other: member of advisory board; Sanofi: Honoraria; GSK: Honoraria, Other: member of advisory board; Amgen: Honoraria, Other: travel support and advisory board ; Abbvie: Honoraria; Janssen: Honoraria, Other: member of advisory board, travel support. Vincent: Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Rigaudeau: Takeda: Membership on an entity's Board of Directors or advisory committees. Boccaccio: celgene: Current holder of individual stocks in a privately-held company. Decaux: Amgen BMS Celgene Janssen Sanofi Takeda: Honoraria.

Abstract: Introduction: The autologous anti-CD19 chimeric antigen receptor (CD19 CAR) T-cells demonstrated significant clinical benefits and a manageable safety profile in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), with an ORR of 52-83% and CR of 40-58% in the 3 pivotal clinical trials (ZUMA-1, TRANSCEND-NHL-001, JULIET), leading to a rapid approval in third line R/R DLBCL in Europe and in USA. The CD19 CAR T-cells Axicabtagene and Tisagenlecleucel have been approved in France since June 2018 for patients with DLBCL, primary mediastinal B-cell lymphomas (PMBL) and transformed FL (tFL), recurrent or refractory after 〉 2 systemic therapy lines. However, all patients are not deemed eligible for such therapy. Here we describe the characteristics of the non-eligible patients and the causes of non-eligibility for CD19 CAR T-cells at our center. Methods: We performed a retrospective analysis of all patients for whom our center was contacted for potential eligibility to CD19 CAR T-cells. Upon each request, a screening form was completed by the referring hospital to validate the indication (DLBCL, PMBL or tFL; recurrent or refractory to 〉 2 systemic therapy lines) and the absence of contra-indications (CNS involvement (MRI mandatory), active infection). The patient was then evaluated in our hospital to check the predetermined eligibility criteria: age, comorbidities, LVEF 〉 45%, no pericarditis or cardiogram abnormality, creatinine clearance 〉 60 mL/min, ALT/AST 〈 2.5 N, total bilirubin 〈 1.5 mg/dL, no pleural effusion, SpO2 〉 92% without oxygen, lymphocytes 〉 100/µL, no rapid progressive disease (compressive mass, PS 〉 2 or rapid increase of LDH), or no active neurological/auto-immune disease. In case of severe comorbidities or age 〉 70, patient's frailty index was assessed by an ICU physician. Eligibility was then finally validated by our local board through a careful case-by-case analysis. Results: Between June 2018 and July 31, 2019, 221 requests were analyzed. Evaluation is still ongoing for 6 patients (3%). 80/215 patients (37%) were deemed eligible for CAR T-cells, 58 patients (27%) were excluded before any visit at the expert hospital because of histology other than DLBCL, PMBL and tFL (n=30: non-transformed FL 9, transformed SLL/CLL 7, transformed Waldenström 3, transformed MZL 3, MZL 2, primary CNS lymphoma 2, SLL/CLL 1, HL 1, lymphoblastic lymphoma 1, CD19- 1), 〈 2 previous lines (n=7), CNS involvement (n=7), administrative reason (n=14). The remaining 77 patients (36%) were deemed non-eligible for CAR T-cells after the first visit. Median age was 59 years (range 18-86, 41% ≥ 65 years), 68% were male. There were 62, 4 and 2 patients with DLBCL, PMBL and tFL, respectively. Median number of prior lines was 3 (range 2-11, 43% 〉 3 lines), 86% of patients presented with a primary refractory disease. Nine patients were with a refractory disease despite stem cell transplantation (SCT, 5 autologous, 3 allogeneic and 1 both). Considering these 77 patients, 12 (16%) had 2 concomitant causes of non-eligibility. Overall, the two main causes of non-eligibility were rapid disease progression (n=49) and major frailty (n=23), including 10 patients with 11 severe organ dysfunctions [5 cardiac, 3 kidney, 1 liver, 1 respiratory and 1 heavy engine handicap]. Replicative viral infections (n=4) constituted also an important cause of frailty: HIV (1), HBV (2), HBV + HCV (1). Two patients had a solid organ transplantation requiring immunosuppressive drugs. Advanced neurological diseases (n=4) included: extrapyramidal syndrome (3), advanced multiple sclerosis (1). Active autoimmune diseases were a cause of frailty for 2 patients: thyroiditis (1), periodic fever (1). In one patient, the screening evaluation showed a concomitant malignancy. Other causes of non-eligibility were found in 17 patients: complete remission after the salvage therapy (n=7), age 〉 80 (n=4), severe thrombocytopenia 〈 20 G/L (n=2), no slot available (n=1), patient refusal (n=3). Outcomes of the non-eligible patients (alternative treatments, survival) will be presented at the meeting. Conclusion: In this pioneering experience, 37% of patients in whom a CAR T-cell request is made are ultimately deemed eligible for the therapy. Other patients are either rapidly excluded based on lack of CAR T-cells indications (27%), or deemed non-eligible because of failure to control the disease / major frailty (36%). Disclosures Paillassa: Janssen: Other: Bibliography board with young hematologists. Di Blasi:Novartis: Honoraria. Casasnovas:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Merck Sharp and Dohme: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cartron:Roche, Celgene: Consultancy; Sanofi, Gilead, Janssen, Roche, Celgene: Honoraria. Feugier:gilead: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau; janssen: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau. Gyan:Pfizer: Honoraria. Haioun:novartis: Honoraria; celgene: Honoraria; roche: Consultancy; celgene: Consultancy; gilead: Consultancy; takeda: Consultancy; janssen cilag: Consultancy; amgen: Honoraria; servier: Honoraria. Thieblemont:Roche: Honoraria, Research Funding; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; Novartis: Honoraria.

Abstract: Rituximab, a chimeric monoclonal antibody directed against the CD20 antigen is widely used for the treatment of B-cell malignancies and others auto immune pathologies. HBV reactivation is a well known life-threatening complication of rituximab. In 2004, US FDA recommended HBV screening of high risk patients before the first Rituximab infusion and treatment of patients with positive hepatitis B surface antigen or antibody to hepatitis B core. Then in 2008, CDC recommended screening of all patients. EASL in 2012 recommended treating patients with positive HBsAg or anti-HBc. The aim of this study was to evaluate HBV screening and management before the initiation of rituximab. We conducted a retrospective monocentric study in Argenteuil Hospital, located in the neighborhood of Paris, France. All patients who received rituximab between January 1, 2008 and December 31, 2013 were included. The list was exhaustive through the Pharmacy Informatics. Laboratory Informatics gave test dates and results for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antibody (anti-HBc) and antibody to hepatitis B surface (anti-HBs). We investigated for medical record when serology was missing. We considered serology as not done when no result was found. The data are described as number and percentages for categorical variables and mean ± standard deviation or median for continuous variables. Between-group comparisons were done using the chi-square test for categorical data and Student t-test for continuous data. P values 〈 0.05 were considered statistically significant. Statistical analysis was performed with R software (http://cran-project.org). We included 509 patients with a mean age of 65.5 when rituximab treatment was initiated. Men represented 58% and 33% of patients were born outside of France, mainly in Africa or in Asia. Rituximab was mainly used in cancer treatment (91%) and chemotherapy was associated in 82% of cases. Five medical records were lost, so the study was conducted for 504 patients. The rate of assessment for HBV serology was 79.4% (104 not done among the 504). Sex, country of origin, indication for treatment or cancer were not statistically significant for the quality of screening. No difference was found depending on the period. A trend in favor a worst screening for older patients was seen: median age for screening patients was 64.8 versus 68.1 (p=0.053). Among the 9 patients who were HBsAg+, 8 received analogue nucleoside and did not reactivate HBV. These patients have also been screened for Hepatitis Delta virus. The patient who did not receive a preemptive therapy reactivated HBV. This patient was initially treated in another center without HBV screening. When he was referred to us an important hepatic flare secondary to HBV reactivation was found. Six among the 11 patients who were anti-HBc+ /antiHBs- received preemptive therapy and no reactivation was seen. Adenofovir then tenofovir was chosen preferentially. None of the patients with anti-HBc and anti-HBs received preemptive antiviral therapy as recommended since 2004. Among them, one patient treated with rituximab and chlorambucil for CLL reactivated HBV. Evolution was favorable on entecavir. To summarize, our HBV management before Rituximab first infusion must be improved. All patients with HBc with or without HBs antibody are of risk of HBV reactivation. Pre-emptive treatment should be proposed to all patients with HBc positive antibody. Disclosures No relevant conflicts of interest to declare.

Abstract: Abstract 3869 Poster Board III-805 Introduction The outcome of patients with plasma-cell leukemia (PCL) is poor. Avet-Loiseau reported on behalf the IFM, our first experience in PCL patients and showed that the median overall survival (OS) was 8 months (Avet-Loiseau, Blood, 2001). Since 1999, novel agents such as Thalidomide, Bortezomib (Velcade) or Lenalidomide (Revlimid) have been widely used in the treatment of multiple myeloma, both at the time of relapse or part of upfront therapy. Patients and methods In this retrospective analysis, we have looked at the outcome of PCL patients treated within the IFM since 1999 in order to study the impact of novel agents on survival. Results 31 cases, 20 males, 11 females, median age 55 years (34-78) were analyzed. Twenty one patients less than 65 years received high-dose therapy as part of frontline treatment : 19 autologous haematopoietic stem cell transplantation (HSCT) and 5 allogeneic transplantation. Novel agents were used part of induction therapy in 6 cases, at the time of relapse for 9 patients, for both induction and relapse in 16 cases. Thirteen patients received 1 novel agent, 11 received 2 and 7 patients received the 3 novel agents. The median number of lines of therapy was 2 (1 to 4). Bortezomib was used as up front treatment in 15 patients and at relapse for 9 patients. Overall response rate according the IMWG criterias was 70% (17/24) including 11 CR or VGPR (45%). PAD (Bortezomib, Adriamycin and Dexamethasone) and VTD (Bortezomib, Thalidomide, Dexamethasone) regimens provided the best response rates. Lenalidomide was used in 13 patients mostly at relapse. A response was obtained in 53% of patients including 2CR and 2 VGPR (30%). Nineteen patients were treated with Thalidomide-based regimens. Overall response rate was 52% (10/19) including 2 CR and 6 VGPR (31%). Overall, for the whole group of patients, the median progression-free survival was 8 months (0-26) and the median OS was 15 months (6-108). When comparing this survival with that described in our previous experience reported before 1999, we clearly showed that the use of novel agents improved the survival of patients with PCL. Conclusion In this retrospective study, novel agents improved the prognosis of P-PCL. Prospective IFM phase II studies are ongoing to confirm these results. Disclosures: No relevant conflicts of interest to declare.

Abstract: Introduction In immune thrombocytopenia (ITP), isotopic assessment of the site of platelet destruction using autologous111Indium-oxinate-labelled platelet sequestration study could be an helpful parameter to determine whether or not to perform splenectomy. Two independent studies have suggested that a purely splenic sequestration could be a significant predictive factor of long-term complete response after splenectomy. An increasing number of patients receives thrombopoietic receptor-agonists (TPO-RAs) but such treatments are not curative and therefore do not necessarily prevent from considering splenectomy in the course of ITP. TPO-RAs increase platelet production by inducing proliferation and differentiation of the megakaryocyte lineage. We have only very few data evaluating the impact of TPO-RAs, on mean platelet life span (MPLS), platelet production and platelet site of destruction. The aim of this study was to assess these parameters and clinical outcome of patients treated with TPO-RAs who underwent kinetic study of autologous111Indium-oxinate-labelled platelet. Patients and Methods We carried out a retrospective study in the Ile de France region, between 2008 and 2016. Patients were retrospectively selected from a prospective clinical database at the Cellular Biology Department of Saint Louis Hospital. We selected adult patients with definite ITP according to the international criteria. The isotopic method used to study platelet lifespan was previously described. Analyses were based on the radioactivity accumulation slopes in the hepatic or splenic area. We excluded patients who had received less than 3Mbeq of 111In. Data from patients' medical charts were collected using the standardized form of the Referral Center for Adult ITP. Complete response (CR) and Response (R) were defined according to standardized international criteria: platelet count 〉 30x 109/L with at least a doubling of the baseline value or 〉 100 x 109/L. Results of platelet kinetic study from patients treated with TPO-RAs were compared with those from patients receiving no treatments. Results Two hundred and fifty three adults ITP patients were included. At the time of platelet kinetic study, 24 patients (10 men/14 women) with a median age of 63 years [range: 22-83] were treated with TPO-RAs (romiplostim n= 10, eltrombopag n = 14) and 229 (81 men/148 women) had no treatment. Among the TPO-RAs treated patients, some also received low dose steroids (n=6), dapsone (n=1) or intravenous immunoglobulins (n=2) at least two weeks before the kinetic study. Three were newly diagnosed, 9 had persistent ITP and 12 chronic ITP. The median platelet count was 62 x109/L [range: 22-175] , and 7 patients had a platelet count 〉 100 x109/L. The median Mean Platelet Life Span (MPLS) was reduced in both groups (1.44 day [range: 0.4-7.5] (normal: 7-10) in patients treated with TPO-RAs), but was significantly higher in untreated patients (2.3 day [0.4-11] , p = 0.004). The median turnover platelets ratio was increased in both groups (48% per day [range: 11-173] in patients treated with TPO-RAs), but was significantly lower in untreated patients (30% per day [range: 0.8-247] ). Ratio of platelet production was significantly increased in patients treated with TPO-RAs (median: 2, [range: 0.1-5.0]) compared with untreated patients (median: 0.84, [range: 0.1-85.0] ). Repartition of the site of platelet sequestration was similar in the two groups, 12 (50%) patients treated with TPO-RAs had a splenic uptake, versus 112 (49.1%) in untreated patients, and 2 (20%) patients treated with TPO-RAs had an hepatic uptake versus 9 (3.9%) in untreated patients. A splenectomy was performed in 9 out of the 12 patients with a purely splenic sequestration. After a median follow-up of 26 months [range 0-53], 8 (88%) had achieved CR and 1 had relapsed 5 months after splenectomy. Conclusion Our study shows that despite an increase production and turnover of platelets due to the stimulation of the megakaryopoiesis by TPO-RAs, the MPLS was clearly reduced and the repartition of platelet sequestration was not modified in patients receiving these drugs. Moreover, it would seem that a purely splenic sequestration is also predictive of CR after splenectomy in this group of patients. More importantly platelet kinetic study can be used in patients treated with TPO-RAs to position the splenectomy in the therapeutic management. Disclosures No relevant conflicts of interest to declare.

Abstract: Background Induction therapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with symptomatic multiple myeloma less than 66 years old. The quality of response to the induction treatment is an important prognostic factor and is predictive of progression free survival (PFS) following ASCT. The triplet combinations bortezomib-thalidomide-dexamethasone (VTD) and bortezomib-cyclophosphamide-dexamethasone (VCD) have demonstrated high response rates in prospective phase 2 and phase 3 clinical trials, they are 2 of the most commonly used induction regimens prior to ASCT, and are both recommended in the International guidelines. To date, no comparative data from prospective randomized trials of the safety and efficacy of VTD vs VCD are available. This provided the rationale for the phase 3 investigation of VTD vs VCD prior to ASCT in patients with de novo MM in this randomized multicenter study (NCT01564537). Methods Patients with de novo symptomatic MM less than 66 years old were prospectively randomized to receive either 4 cycles of VTD (arm A) or 4 cycles of VCD (arm B) followed by ASCT. The VTD regimen consisted of four 21-day cycles of bortezomib 1.3 mg/m²/d, subcutaneously (SC) D1, 4, 8 and 11, Dexamethasone 40 mg/d, PO D1 to 4, D9 to 12 and Thalidomide 100 mg/d, PO D1 to D21. The VCD regimen consisted of four 21-day cycles of bortezomib 1.3 mg/m²/d, SC D1, 4, 8 and 11, Dexamethasone 40 mg/d, PO D1 to 4, D9 to 12 and Cyclophosphamide 500 mg/m²/d, PO D1, 8, 15. Patients were stratified according to ISS (1-2 versus 3) and cytogenetics (high-risk defined by 17p deletion and t(4;14) versus other).The primary endpoint was very good partial response (VGPR) rate following 4 cycles. Response was assessed in a central lab according to the IMWG criteria. Assuming a VGPR rate of 60% in the VTD arm versus 45% in the VCD arm (15% difference), the possibility to detect a statistically significant difference required the enrolment of 340 patients overall (170 per arm). Adverse events were graded using the NCI CTCAE catalogue, version 4.0. Results From 11/2013 to 02/2015, 358 patients were enrolled into the study. 18 were screening failures, and 170 were randomized each to arm A (VTD) and arm B (VCD). The median age was 60 years (range, 26-65), 62% of the patients were male, and overall, the patient characteristics were well-balanced across the 2 arms of the study. The median number of induction cycles administered in both arms was 4 (1-4). On an intent-to-treat basis, the overall response rate ( 〉 partial response [PR]) was 92.3% in arm A, including a 10.7% complete response (CR) rate and a VGPR rate of 66.7%, while in arm B the overall response rate was 84%, with a 9.5% CR and a 56.2% VGPR rate. VGPR and PR rates were significantly higher in the VTD arm with p-values of 0.04 and 0.02, respectively. Seven patients died during induction therapy (2%), 3 in arm A from infections (2) and pulmonary embolism (1), and 4 in arm B from progression to extramedullary myeloma (2) and infections (2). Grades 3 / 4 peripheral neuropathy occurred in 4% and 2.2% in Arm A and B, respectively. Grade 3/4 neutropenia was seen in 11.9% vs 22.5% in Arm A and B, respectively. Conclusion This trial is the first prospective randomized comparison of 4 cycles of VTD versus 4 cycles of VCD administered as induction therapy prior to ASCT. VTD was shown to be significantly superior to VCD in terms of VGPR and PR rates. Neuropathy rates low in both arms, while neutropenia was more frequent with VCD. Disclosures Moreau: Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hulin:Celgene Corporation: Honoraria; Janssen: Honoraria; Bristol Myers Squibb: Honoraria; Amgen: Honoraria. MACRO:celgene: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees. Garderet:Bristol-Myers Squibb: Consultancy. Stoppa:Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Facon:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Membership on an entity's Board of Directors or advisory committees. Laribi:Hospira SAS: Research Funding. Avet-Loiseau:jansen: Membership on an entity's Board of Directors or advisory committees; onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees; onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Attal:jansen: Honoraria; celgene: Membership on an entity's Board of Directors or advisory committees.