ALBERT

Description: CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins and disialosyl antibodies) is a rare syndrome characterized by chronic neuropathy with sensory ataxia, ocular and/or bulbar motor weakness, in the presence of a monoclonal IgM reacting against gangliosides containing disialosyl epitopes. Data regarding associated hematologic malignancies and effective therapies in CANOMAD are scarce. We conducted a French multicenter retrospective study that included 45 patients with serum IgM antibodies reacting against disialosyl epitopes in the context of evocating neurological symptoms. Main clinical features were sensitive symptoms (ataxia, paresthesia, hypoesthesia) (n=45, 100%), motor weakness (n=18, 40%), ophthalmoplegia (n=20, 45%) and bulbar symptoms (n=6, 13%). Forty five percent of the cohort had moderate to severe disability (modified Rankin score, 3-5). Cold agglutinins were identified in 15 (34%) patients. Electrophysiological studies showed a demyelinating or axonal pattern in respectively 60 and 27% of cases. All patients had serum monoclonal IgM gammopathy (median, 2.6 g/L; range, 0.1-40). Overt hematologic malignancies were diagnosed in 16 patients (36%), most frequently Waldenström macroglobulinemia (n=9, 20%). Forty-one patients (91%) required treatment for CANOMAD. Intravenous immunoglobulins (IVIg) and rituximab-based regimens were the most effective therapies with respectively 53 and 52% of partial or better clinical responses. Corticosteroids and immunosuppressive drugs were largely ineffective. Although more studies are warranted to better define the optimal therapeutic sequence, IVIg should be proposed as the standard of care for first-line and rituximab-based regimens for second-line treatment. These compiling data argue for CANOMAD to be included in neurological monoclonal gammopathy of clinical significance.

Description: Introduction: CLL is a heterogeneous disease in terms of response to treatment, with some patients reaching complete and prolonged remissions, while others relapsing early and requiring several lines of treatments. This highly variable course is partly explained by the existence of a heterogenic panel of genetic alterations (mutations, chromosomal abnormalities) that allow the development of drug-resistant aggressive CLL subclones. Therefore, a functional characterization of the cytogenetic alterations associated to CLL drug resistance may provide new means of improving the current therapeutic strategies. We and others have already reported that the gain of 2p (2p+) is recurrent in CLL. However, the candidate gained gene(s) on the 2p remain to be identified. Previously data: we have observed that the 2p gain is frequent in previously untreated CLL Binet stages B/C (21/132, 15.9%), and is associated with bad prognostic factors, such as 11q deletion (p=0.0008) and unmutated IGHV (p=0.02). Using a SNP-array approach, we have identified a minimally gained region of 1.28Mb on 2p16.1-15. This region included the gene CRM1/XPO1 (Chromosome Region Maintenance 1/Exportin-1), a gene also recurrently mutated in CLL. A qPCR assessment confirmed that XPO1 was overexpressed in the 2p+/CLL patients (1.4-fold increase compared to 2p-/CLL; p=0.02). The objective of our work was to identify the potential role of XPO1 in CLL drug resistance by using the selective XPO1 inhibitor Selinexor (KPT-330, provided by Karyopharm Therapeutics), which is currently in Phase II human clinical trials in hematological and solid cancers. Methods: We have analyzed 36 2p+/CLL and we have searched for XPO1 mutations in 436 CLL samples. CLL drug resistance associated to XPO1 overexpression/mutation was assessed by measuring the rate of programmed cell death (PCD) on cells from 2p- and wildtype (wt) XPO1/CLL (n=20), 2p+/XPO1 wt/CLL (n=8) and on XPO1 mut/CLL (n=6). After 24 hours treatment with Fludarabin + Cyclophosphamid + Rituximab (FCR), Ibrutinib (Ibru), Idelalisib + Rituximab (Ide+R) and Selinexor, cells were stained with Annexin-V and propidium iodide and PCD was assessed by flow cytometry. KPT-301 was used as a negative control. For the inhibition assay, the inhibitor Q-VD-Oph was added 30 min before inducing cell death. Mitochondrial membrane depolarisation was assessed using tetramethyllrhodamine ethyl ester probe and flow cytometry analysis. Results: (i) Using a FISH approach, we fully confirmed the gain of XPO1 in 2p+/CLL samples. Additionally, we found that the XPO1 gain was often subclonal, suggesting that it tends to arise late in leukemic development. Longitudinal FISH analyses, performed on 8 2p+/CLL-treated patients, showed a similar or increasing percentage of cells carrying XPO1 gain at relapse, when compared to diagnosis; (ii) XPO1 was mutated in 23/436 (5.3%) CLL and in 2/30 (6.7%) 2p+/CLL; (iii) Selinexor induced PCD in 2p-/XPO1 wt/CLL (35% of PCD). The results were similar in all tested CLL, independently of prognostic factors (del13q, tri12, del11q, del17p, IGHV status), while sparing the non leukemic cells from patients or B cells from healthy donors; (iv) Selinexor induced CLL PCD through a caspase-dependant apoptotic pathway, as evidenced by inhibition of cell death by Q-VD-Oph, and cleavage of the caspase-3. Selinexor also induced mitochondrial depolarization and was associated with upregulation and activation of the pro-apopototic Bax protein; (v) XPO1 mut/CLL were significantly resistant to PCD induced by Selinexor (p=0.003). In contrast, the mutations in XPO1 had no effect in FCR and Ibru PCD induction; (vi) 2p+/CLL cells were resistant to PCD induced by all tested drugs: FCR (p=0.01), Ibru (p=0.003), Ide+R (p=0.004) and Selinexor (p=0.0001). Conclusion: Our data show that 2p+/CLL is associated to FCR, Ibru and Ide+R drug resistance. Strikingly, Selinexor, a new XPO1 inhibitor, is unable to induce PCD in 2p+ and/or XPO1 mut CLL, which strongly suggests a key role for XPO1 in the CLL drug resistance associated to the 2p gain. Altogether, our work provide substantial progress in the understanding of the role of XPO1 in CLL drug resistance and suggests that the assessment of the 2p gain and the mutations in XPO1 will be considered before to decide a CLL therapy. As 2p gain could be observed in other B malignancies, it is tempting to extend these recommendations to all Selinexor treatments. Disclosures Choquet: Janssen: Consultancy; Roche: Consultancy. Leblond:Janssen: Consultancy, Honoraria, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; Mundipharma: Honoraria.

Description: Background: The novel, glycoengineered type II anti-CD20 monoclonal antibody, obinutuzumab (GA101) has demonstrated superior efficacy to chlorambucil (Clb) monotherapy and to Clb in combination with rituximab (R-Clb) with an acceptable safety profile in CLL. However, an increased rate of infusion-related reactions (IRRs) has been observed with the obinutuzumab(G)-Clb combination compared with R-Clb during the first cycle of treatment. The GREEN study (NCT01905943) is an ongoing phase IIIb, multicenter, open-label trial investigating the safety and efficacy of obinutuzumab alone or in combination with chemotherapy in patients with previously untreated or relapsed/refractory CLL. We report safety data from cohort 1, which aimed to reduce IRRs on the first day of obinutuzumab administration in previously untreated patients using a lower dose and slower infusion rate than in previous studies. Methods: Subjects aged ≥18 years withdocumented CLL, an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2 and adequate hematologic function are enrolled. Treatment includes obinutuzumab (1000mg) administered intravenously on days (D) 1 (25mg) and 2 (975mg), D8, and D15 of cycle (C) 1, and on D1 of C2–6, alone (any patient: n=18) or in combination with 28-day cycles of chemotherapy: fludarabine plus cyclophosphamide (FC; n=46) for fit patients (cumulative illness rating scale [CIRS] ≤6 and creatinine clearance [CrCl] ≥70mL/min), Clb (n=8) for unfit patients (CIRS 〉6 and/or CrCl

Description: Background: PIOL, now named “primary vitreo-retinal lymphoma”, is a very rare subset of non Hodgkin lymphoma, usually arising in elderly patients and characterized by a high level of relapse, mainly in the first year, with more than 20% of cases relapsing in brain, and a short survival. There is no consensus on treatment procedures, even in first line, and prospective comparative studies do not exist. Classical attitudes are systemic chemotherapy (SC), often high dose methotrexate, radiotherapy or intraocular injection of methotrexate but publication on R/R PIOL are exceptional. New treatments are necessary, especially with a good tolerance profile. As Temozolomide (Te) hassome efficiency on primary-central-nervous-system lymphoma (PCNSL) we used this drug in R/R PIOL in our center. Methods: Inclusion criteria were R/R PIOL and/or PIOL not eligible for IV chemotherapy. Diagnosis was established on cytological and molecular analysis after vitrectomy, and the absence of brain or meningeal localization verified by MRI and lumbar puncture. Treatment consisted in Te at 150mg/m2 orally 5 days per month, without corticosteroid use, in absence of any response, dosage was increased to 200mg/m². A complete response was defined as a normalization of eye exam and intraocular interleukins 10 and 6 levels. Results: Sixteen patients were analyzed, 3 males and 13 females, mean age 75 years [35-90]. All but two received systemic chemotherapy with at least high dose methotrexate and high dose cytarabin before Te, 8 were in second line, 4 in third, with 1 patient who relapsed after autologous stem-cell transplantation (ASCT) conditioned by thiotepa, cyclophosphamide and busulfan, and 2 in forth. The 2 patients treated in first line where more than 80 years old. Median duration of treatment was 5 months. The median follow-up (fu) is 16 months. Overall response rate is 75%, with 10 CR (63%) and 2 PR (13%). At the last fu, 7 patients are still in CR, with a median DFS of 13 months. The patient treated after ASCT relapse is still in CR at 62 months. The two old patients treated in first line are in CR at last fu. Two patients where treated a second time by Te after relapse, obtaining 2 new CR, one of 4 months, one persistent at 14 months. Median OS is not reached. Only 3 patients experienced hematological grade 3/4 toxicity. Conclusion: This work represents the biggest study with an homogeneous treatment in R/R PIOL. Temozolomide appears as a safe and efficient treatment of R/R PIOL or in first line in patients in bad condition, even after high dose chemotherapy and/or in elderly patients. Longer follow-up, prospective and larger studies are necessary to confirm these data Disclosures Leblond: Roche: Honoraria, Speakers Bureau.

Description: Introduction: About 2 to 10% of patients (pts) diagnosed with Chronic Lymphocytic Leukemia (CLL) develop diffuse large B-cell lymphoma (DLBCL, so-called Richter transformation (RT)) over long-term follow-up. The outcomes of pts with RT are variable and poorly understood and there is no consensus on the best therapeutic approach. The aim of this study was to analyze the clinical characteristics, outcomes and factors predictive of survival in a large series of RT from the French Innovative Leukemia Organization (FILO). Methods: Biopsy-confirmed RT (limited to DLBCL and excluding Hodgkin lymphoma) diagnosed from 2001 to 2018 were identified from eight FILO centers. Clinical and biological characteristics of CLL and RT at diagnosis, including cytogenetics, clonal relation with the pre-existing CLL, Epstein-Barr virus (EBV) status, cell of origin (COO) analyzed by immunohistochemistry and RT score (Tsimberidou AM et al, J Clin Oncol, 2006) were analyzed as well as treatment and outcomes. Overall survivals (OS) were defined as time from CLL and RT diagnosis to death from any cause and analyzed using the Kaplan-Meier method. Statistical analyses were performed with SAS version 9.4. Results: A total of 70 CLL pts who developed RT were identified. The median age at CLL diagnosis was 62 years old (range 35-82), and 50 (71.4 %) were male. The median time to transformation was 5.5 years (range 0 to 22 years), with 12 simultaneous diagnosis of CLL and RT. Prior to RT, 20 (29%) pts had not been treated for CLL, 50 received one (n=21) or more (n= 29) line of treatment ; 6 pts had received a novel agent (ibrutinib, idelalisib or venetoclax). The median age at RT diagnosis was 68 years old (range 42-88). All biopsies were centrally reviewed; 38/58 pts (66%) had elevated LDH (〉1.5N) ; 35/65 pts (54 %) had bulky disease (≥ 5 cm); 10/54 (18.5%) pts had del(17p) or TP53 mutation ; 9/42 pts (21%) had a complex karyotype (at least 3 abnormalities). The CLL and RT were clonally related in 27/27 (100%) tested pts. COO by Hans algorithm was non germinal center B cell-like (GCB) in 26/28 pts (93%). EBV was positive or detected in 5/40 (12.5%) pts. The median of Ki67 positivity was 70% (range 30% to 100%). The RT score (based at RT diagnosis on ECOG performance status 2-4, LDH 〉1.5 x normal, platelets5 cm and 〉1 prior therapy for CLL) was : low risk in 17 pts (31%), low-intermediate risk in 10 pts (19%), high-intermediate risk in 14 pts (25%) and high risk in 14 pts (25%). The most common first-line treatment of RT was immunochemotherapy (n=57, 87%) including R-CHOP-like regimen (n=48, 73%). Autologous or allogeneic transplantation was performed for 7 pts (11%). Response to first-line treatment was complete or partial response in 26 pts (40%), and stable disease or progression in 39 pts (60%). After a median follow-up of 8 years, 51/64 pts (80%) have died. The main causes of death were progressive DLBCL (n=36, 71%), infection (n=8, 16%) or progressive CLL (n=2, 4%). The median OS of the cohort from CLL and RT diagnosis (Figure 1) were 7.8 years and 9.5 months, respectively. In univariate analysis, patients with TP53 disruption at CLL stage, low platelets count, elevated LDH, elevated beta2-microglobulin, high ECOG score, high RT score, EBV positivity and absence of response to first-line RT treatment had worse OS. The ECOG score, platelets count and TP53 disruption remain significant in multivariate Cox-regression. Last, we compared the clinical and biological parameters of two Richter groups defined as: (i) short-term survivors (48 months, n = 18). Long survival was significantly associated with elevated platelets count, low LDH, low ECOG, low RT score and response to RT first-line treatment. Discussion: The clinical outcomes of RT patients is poor and novel treatment options are needed. However, a group of long-term survivors was identified, characterized by elevated platelets count, low LDH, low ECOG, low RT score and response to immunochemotherapy. Disclosures Leblond: Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees. Cymbalista:Janssen: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; Sunesis: Research Funding; Roche: Research Funding; Abbvie: Honoraria. Guièze:Abbvie: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Roche: Honoraria. Broseus:Janssen: Honoraria; Gilead: Honoraria; Novartis: Research Funding. Feugier:gilead: Honoraria, Research Funding, Speakers Bureau; janssen: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau.

Description: Background: B-PTLD is a rare but severe complication observed after organ transplantation. There is no consensus on treatment modalities in this setting but Rituximab monotherapy has been presented as an effective and well tolerated treatment. Long term efficacy is unknown. Aim: We recently published results of the first prospective study on PTLD treatment, using four weekly injection of Rituximab in progressive or non responding tumours after immunosuppression diminution (Blood2006; 107; 3053–7). We present here update results up to 6 years after inclusion. Methods: From may 2000 to December 2001, 43 PTLD after solid organ transplantation have been enrolled in M39037, a franco-belgian multicentric prospective trial. The primary end point was day 80 response rate and one year results were also presented. Participating centres were contacted in order to obtain update data on surviving patients at one year, especially for their tumour status (complete response (CR), partial response (PR) or progressive disease (PD)), date of last information, eventual death and cause of death. Results: At one year, on 43 included patients, 26 were still alive, 12 in CR or Cru, one in PR, 10 in PD and two with insufficient information. At this time, update data are available on eight patients, six were in CR or Cru at one year and two in PD. Five patients died by organ failure (n=1), graft rejection (n=1), sudden death (n=2) or heart biopsy complication (n=1); all but one were in CR at this time. Three patients are still alive and in CR. No relapse has been diagnosed and median survival is 1188 days (with a median follow up of 1689 days for surviving patients). Final analysis on all patients will be presented at the ASH meeting. Conclusion: Rituximab in monotherapy seems to have a durable efficacy on PTLD after solid organ transplantation with a follow up of more than 4,5 years. Complete results will be presented at the ASH Meeting.

Description: Background Cytogenetic abnormalities are of key importance for predicting clinical course and response to therapy in patients with chronic lymphocytic leukemia (CLL). Trisomy 12 (tri12), the third most frequent chromosomal aberration in CLL patients (10-20%), is associated with an intermediate prognostic risk but represents a clinical heterogeneous entity. Recently, next generation sequencing have revealed recurrent mutations in genes that were unknown to be involved in CLL pathogenesis, including NOTCH1, MYD88, SF3B1, XPO1 and BIRC3. In patients harboring tri12, NOTCH1 mutations have been shown to be present in up to 25% of cases and to confer unfavorable outcome explaining in part the clinical heterogeneity of tri12 patients. To better understand the genetic basis and prognosis of tri12 patients, we performed a multicenter retrospective study combining extensive mutational and cytogenetic analysis. Methods Patients carrying tri12 were identified using fluorescence in situ hybridization (FISH) and/or chromosome banding (CB). Main clinical and biological characteristics were collected and included in univariate analysis of prognostic factors, comprising age, Binet stage (A vs. B-C), splenomegaly, lymphocyte doubling time (LDT), LDH, beta2microglobulin (B2M), CD38 expression, IGHV mutational status, percentage of interphase nuclei positive (INP) for tri12, additional FISH (del13q, del11q, del17p) or chromosomal aberrations and presence of complex karyotype (〉 2 CB abnormalities). Search for mutations was performed by Sanger direct sequencing for TP53 (exons 5-10), NOTCH1 (exon 34), MYD88 (exons 14-16), SF3B1 (exons 14-16) and XPO1 (exons 14-15). Primary and secondary endpoints were time to first treatment (TFT), response to therapy, time to next treatment (TNT) and overall survival (OS). Results The study population comprised a total of 177 untreated patients including 112 and 75 patients with stage A and B-C CLL, respectively. The median age at diagnosis was 62 years old (range, 31-87) and 33% of patients were female. B2M was superior to 4 mg/L in 30/92 (32%) patients and LDH elevated in 65%. CD38 expression was positive (〉30%) in 58% and IGHV status was unmutated in 60%. Among the whole study population, all patients were positive for tri12 by FISH and 158/165 by CB. Tri12 was associated by CB with tri19 in 21 patients (13.2%), tri18 in 12 patients (7.5%), tri3 in 1 patient (

Description: B-PLL is defined by the presence of prolymphocytes in peripheral blood exceeding 55% of lymphoid cells. The diagnosis, mainly based on clinical and morphological data, can be difficult because of overlap with other B-cell malignancies. Because of the rarity of the disease, only case reports and small series describe its cytogenetic features. Few prognostic markers have been identified in this aggressive leukemia usually resistant to standard chemo-immuno therapy. We report here the cytogenetic and molecular findings in a large series of B-PLL. We also studied the in vitro response to novel targeted drugs on primary B-PLL cells. The study included 34 cases with a diagnosis of B-PLL validated by morphological review performed by three independent expert cytologists. The diagnosis of mantle cell lymphoma was excluded by karyotype (K) and FISH using CCND1, CCND2 and CCND3 probes. Median age at diagnosis was 72 years [46-88]. K was complex (≥3 abnormalities) in 73%, and highly complex (HCK≥5) in 45%. Combining K and FISH data, the most frequent chromosomal aberrations were: translocation targeting the MYC gene [t(MYC)] (21/34, 62%), 17p deletion including TP53 gene (13/34, 38%), trisomy 18/18q (10/33, 30%), 13q14 deletion (10/34, 29%), trisomy 3 (8/33, 24%), trisomy 12 (8/34, 24%) and 8p deletion (7/31, 23%). Whole-Exome Sequencing analysis of paired tumor-control DNA was performed in 16 patients. The most frequently mutated genes were TP53(6/16, 38%), associated with del17p in all, MYD88 (n=4), BCOR (n=4), MYC (n=3), SF3B1 (n=3), FAT1 (n=3), SETD2 (n=2), CHD2 (n=2), CXCR4 (n=2), BCLAF1 (n=2) and NFASC (n=2). Distribution of the chromosomal aberrations is shown in Fig 1. The main group of patients (21/34, 62%) had a t(MYC) that was associated with a higher % of prolymphocytes (86 vs 76, p=0.03), CD38 expression (90% vs 15%,p

Description: Results to date indicate that high-dose therapy (HDT) with autologous stem cell support improves survival of patients with symptomatic multiple myeloma (MM). We performed a multicenter, sequential, randomized trial designed to assess the optimal timing of HDT and autotransplantation. Among 202 enrolled patients who were up to 56 years old, 185 were randomly assigned to receive HDT and peripheral blood stem cell (PBSC) autotransplantation (early HDT group, n = 91) or a conventional-dose chemotherapy (CCT) regimen (late HDT group, n = 94). In the late HDT group, HDT and transplantation were performed as rescue treament, in case of primary resistance to CCT or at relapse in responders. PBSC were collected before randomization, after mobilization by chemotherapy, and, in the two groups, HDT was preceded by three or four treatments with vincristine, doxorubicin, and methylprednisolone. Data were analyzed on an intent-to-treat basis using a sequential design. Within a median follow-up of 58 months, estimated median overall survival (OS) was 64.6 months in the early HDT group and 64 months in the late group. Survival curves were not different (P = .92, log-rank test). Median event-free survival (EFS) was 39 months in the early HDT group whereas median time between randomization and CCT failure was 13 months in the late group. Average time without symptoms, treatment, and treatment toxicity (TWiSTT) were 27.8 months (95% confidence interval [CI]; range, 23.8 to 31.8) and 22.3 months (range, 16.0 to 28.6) in the two groups, respectively. HDT with PBSC transplantation obtained a median OS exceeding 5 years in young patients with symptomatic MM, whether performed early, as first-line therapy, or late, as rescue treatment. Early HDT may be preferred because it is associated with a shorter period of chemotherapy. © 1998 by The American Society of Hematology.

Description: Abstract 3872 Poster Board III-808 Introduction POEMS syndrome is a rare disease characterized by peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cells, skin changes, papilledema, volume overload, sclerotic bone lesions, thrombocytosis, and high serum VEGF level. Efficient treatments consist in irradiation for patients with localized solitary plasmocytoma and high-dose chemotherapy with autologous stem cell transplantation for appropriate candidates without a focal lesion. Conventional myeloma chemotherapy can only control the disease in a limited number of patients. Results of monoclonal anti-VEGF antibodies, which seem to be attractive due to the role of VEGF in this disease, are controversy with efficacy in 3 patients but treatment related deaths in 2 other patients. Thalidomide effectiveness has been reported in Japanese patients but enthusiasm for its use is tempered by the high incidence of thalidomide-induced peripheral neuropathy. Lenalidomide, which efficacy has been described in one observation (Dispenzieri, Blood 2007 110: 1075-1076), has the advantage of being anti-angiogenic, cytotoxic to malignant plasma cells and with a much lower risk of peripheral neuropathy. We reported here a multicentric French experience with this drug in POEMS syndrome. Patients and Methods There were 3 women and 6 men treated with Lenalidomide in 7 French centres. Median age was 60 (41-76). All patients had sensitive polyneuropathy with motor deficiency in 5 patients. A monoclonal component was present in all cases (IgA lambda in 7 patients, IgG lambda and lambda light chain only in 1 patient each). Other manifestations of POEMS syndrome included sclerotic bone lesions in 6 patients, endocrinopathies in 7 patients, skin changes in 8 patients, oedema in 7 patients, organomegaly in 5 patients, papilledema in 5 patients, thrombocytosis in 3 patients. VEGF serum level was elevated in 4 among 5 patients with a dosage. Previous treatments were high-dose chemotherapy with autologous stem cell transplantation in 3 patients, Melphalan-Prednisone in 3 patients because of advanced age, and prolonged steroid treatment in 2 patients. One patient received Lenalidomide as primary treatment before high-dose therapy. Lenalidomide was given during 21 days each month and sequentially associated with dexamethasone, 5 patients received 25 mg/day and 4 patients received 10 or 15 mg, for a median of 5 cycles (1 to 11). Results Serious side effects were noted in 3 patients with 2 hematologic toxicities (grade III and IV) and a cutaneous allergy. Six patients could be evaluated for hematologic response and all responded, complete response in 3 patients and partial in 3 (〉25%). Clinical responses occurred early, before 3 months of treatment, in 6 cases among 8 (1 patient is not yet evaluable), with a marked improvement in performance and in neurological syndrome. Other manifestations of POEMS syndrome improved, especially oedema in 5 cases among 6. VEGF level (normal value 〈 500 pg/ml) could be serially measured in 4 patients with a normalization in 1 patient and a significant decrease in 3 patients, median 7100 pg/ml (2100-10100) before treatment to 887 pg/ml (304-3270). In 1 of these 3 patients VEGF level increased to initial value while he was still taking Lenalidomide. A second patient experimented a relapse 5 months after ending Lenalidomide, he is still in good response after Lenalidomide reintroduction. With a median follow-up of 12 months (1-26) all patients are alive. Conclusion Lenalidomide seems to be a very promising therapy in POEMS syndrome. It should be tested in larger studies in patients with a systemic disease, who are not able to receive high dose therapy, in relapsing patients and before high dose treatment to avoid transplant related morbidity, particularly engraftment syndrome. Disclosures: Jaccard: Celgene: Membership on an entity's Board of Directors or advisory committees. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees and Speakers Bureau. Moreau:Celgene: Membership on an entity's Board of Directors or advisory committees. Fermand:Celgene: Speakers Bureau.