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International audience; Smoldering multiple myeloma (SMM) is a heterogeneous group of asymptomatic plasma cell disorder characterized by the presence of monoclonal protein >= 30 g/L and/or 10-60% of bone marrow plasma cells and no evidence of SLiM-CRAB criteria according to the 2014 International Myeloma Working Group (IMWG) recommendations. Once the effort to reclassify SMM with active disease as MM requiring treatment was completed, the need to redefine new high-risk SMM arose. The 20/2/20 and the IMWG risk model with the add-on high-risk cytogenetic abnormalities allow to identify high-risk SMM with 50% risk of progression to MM within 2 years, and therefore might help to propose a better therapeutic approach, either with the goal to << cure >> by profoundly debulk the MM with aggressive therapies, or alternatively to restore the immune surveillance like a << delay >> strategy with immune-based therapies. The debate is still ongoing but clearly challenges the watch-and-wait standard of care.

Primary or secondary immune deficiency (ID) is a risk factor, although rare, to develop Waldenström macroglobulinemia (WM). We aimed to better understand the incidence of this occurrence in the real-life and the outcome of either entity. We conducted a review of 194 WM in the Poitou-Charentes registry and identified 7 (3.6%) with a prior history of ID. Across the 7 WM with ID, 4 progressed to active WM disease and required treatment for WM with a median time between WM diagnosis and the first treatment of 1.5 years (range 0-3). The median time from ID to WM occurrence was 8 years (1-18). WM could develop from ID, although a rare event. Our first action was to systematically decrease immunosuppression with long-term control of ID. Half of indolent WM remained indolent despite ID and for remaining WM none appeared of poor risk WM.

The multiple myeloma (MM) non transplant eligible (NTE) population is growing in line with the aging of the population in Western countries. Historically, this population has been known for having a greater risk of treatment related toxicity, and therefore drug development was slow and rather oriented towards the improvement of safety profile than the optimization of disease control. However, NTE MM patients, at least for the fit/non frail patients in recent years, seemed to have benefited more from a less palliative care to improve the depth of response and then prolong survival. NTE MM being a quite heterogeneous population, there are still a number of groups of patients that are in need of more efficient therapy, avoiding unnecessary toxicity, particularly for the frail patients. The use of triplet regimen with a melphalan-prednisone (MP) backbone has long been the standard of care for NTE MM, often dedicated to non-frail patients. New standards of care, triplet, and even quadruplet combinations, are emerging on the basis of the MP backbone but also on the more recently approved lenalidomide-dexamethasone (Rd) backbone. These developments were largely possible in line with the development of antibody-based immunotherapies (IT) in MM. The objective to improve outcomes with an acceptable safety profile will see other key therapeutic developments such as the dropping of dexamethasone early in the disease course or various attempts to allow permanent treatment discontinuation with a prolonged disease control. In that context, it is possible that immunomonitoring, minimal residual disease (MRD), and genomic risk-adaptation will become key elements of the treatment decisions on triplet-based regimens.

Background. Acute myeloid leukemia (AML) incidence increases with age, but elderly patients are often too frail to receive intensive chemotherapy (IC). Instead, treatment with hypomethylating agents (HMAs) is usually proposed, even if they have not demonstrated any real improvement over best supportive care. However, clinical practice has shown a significant difference in overall survival (OS) between responding and non-responding patients to HMAs. Thus, we aimed to assess predictive criteria of HMA response in elderly and frail AML patients. We reviewed the literature for any existing scores: none was found for elderly unfit patients. On the other hand, 3 models/scores existed for fit elderly patients undergoing IC : in the ALFA 9803 trail published by Malfuson and al, the HOCSG model in the MRC AML11 and LRF AML trails by Wheatley and al and finally the MDACC model by Kantarijan and al. Methods. We reviewed all patients aged ≥ 60 years old (y.o) diagnosed with AML, unfit for IC and treated with Azacytidine (AZA) alone in first line from July 2015 to December 2019 in Poitiers' University Hospital. The ineligibility to IC was defined by an age > 75 y.o and/or the appreciation by the physician based on performance status (ECOG) and the evaluation of comorbidities with Charlson Comorbidity Index (CCI). The type of AML (de novo versus secondary) and the 2017 ELN prognosis score were also assessed. Results. Among 63 patients recruited, 86% were older than 70 y.o and 29% older than 80. Frailty criteria were found with a ECOG ≥ 2 in 11 (17%) and a CCI ≥ 3 in 29 (45%) patients. Secondary AML was found in 41 (63%) of patients. Adverse karyotype was detected in 21 (32%) patients and 2017 ELN score was quoted as adverse in 25 (38%) patients. After a median follow up of 10.75 months (IQR 3.98 - 17.94) for the whole cohort, median OS was 10.75 months (95%CI 6.37476 - 14.984). Among 54 (86%) evaluable patients, 50 reached some response: at least hematological improvement according to 2003 International Working Group criteria in 20 of them (37%), and stable disease in 30 (55.6%) patients. Patients reaching at least hematological improvement were able to complete a median of 11.5 cycles (IQR 7.5 - 17) vs 6.5 cycles (IQR 3 - 12). Sadly 23 (35%) patients died before achieving 6 cycles. In our cohort the 2017 ELN score failed to predict risk assessment in elderly frail patients. The ALFA model and HOCSG score were also not able to identify treatable patients neither to predict mortality in our cohort. Interestingly the MDACC high-risk category was able to identify the patients who would not benefit from AZA treatment with worst survival rates (HR 3.01; 95%CI 1.04 - 8.79). Conclusion. To date, stratification scores were developed for young fit patients, undergoing IC. Those scores predict poorly response to HMA and OS in unfit patients. In the era of new treatments and combinations with AZA, there is an urgent and growing need for dedicated prognosis model for unfit elderly AML patients. Disclosures Leleu: Bristol-Myers Squibb: Honoraria; Carsgen Therapeutics Ltd: Honoraria; Gilead Sciences: Honoraria; Celgene: Honoraria; Janssen-Cilag: Honoraria; Karyopharm Therapeutics: Honoraria; Merck: Honoraria; Mundipharma: Honoraria; Novartis: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Oncopeptides: Honoraria; Pierre Fabre: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Other: Non-financial support.

Simple Summary Immunotherapy-based treatments have brought many new options in the treatment of multiple myeloma; still, the disease will inevitably relapse as it remains incurable. The development of non-immunologic drugs is therefore still needed, particularly for patients with advanced myeloma who become refractory to most of the drugs available, including immunotherapy. Non-immunologic agents have proven effective in the field for the past 20 years, notably with the advent of cytotoxic drugs and, subsequently, targeted therapy. In this review, we summarize the information currently available on novel generations of non-immunologic agents:proteasome inhibitors, immunomodulatory agents, anti-BCL-2/MCL-1, anti-XPO1, peptide–drug conjugates, and targeted drugs in early-stage development. Abstract Novel treatments are needed to address the lack of options for patients with relapsed or refractory multiple myeloma. Even though immunotherapy-based treatments have revolutionized the field in recent years, offering new opportunities for patients, there is still no curative therapy. Thus, non-immunologic agents, which have proven effective for decades, are still central to the treatment of multiple myeloma, especially for advanced disease. Building on their efficacy in myeloma, the development of proteasome inhibitors and immunomodulatory drugs has been pursued, and has led to the emergence of a novel generation of agents (e.g., carfilzomib, ixazomib, pomalidomide). The use of alkylating agents is decreasing in most treatment regimens, but melflufen, a peptide-conjugated alkylator with a completely new mechanism of action, offers interesting opportunities. Moreover, with the identification of novel targets, new drug classes have entered the myeloma armamentarium, such as XPO1 inhibitors (selinexor), HDAC inhibitors (panobinostat), and anti-BCL-2 agents (venetoclax). New pathways are still being explored, especially the possibility of a mutation-driven strategy, as biomarkers and targeted treatments are increasing. Though multiple myeloma is still considered incurable, the treatment options are expanding and are progressively becoming more diverse, largely because of the continuous development of non-immunologic agents.

Simple Summary The therapeutics of multiple myeloma (MM) have greatly evolved in recent years both in the first-line setting and at relapse, and for both young and older patients. While still being considered as uncurable, MM survival has significantly increased. The development of immunotherapy (naïve and modern) largely contributed to these progresses, providing new effective drug combinations with acceptable toxicity profiles. Interestingly, some traditional concepts remain up to date, such as high-dose melphalan followed by autologous transplant, which can allow treatment intensification for eligible patients. Yet, with innovative response assessment techniques, allowing new response objectives, and treatment associations enabling profound responses, this, too, might be questioned in the near future. As the MM landscape is continuously moving, we sought to provide a review on the recent advances in the field of treatments in 2020. Abstract The survival rate of multiple myeloma (MM) patients has drastically increased recently as a result of the wide treatment options now available. Younger patients truly benefit from these innovations as they can support more intensive treatment, such as autologous stem cell transplant or multiple drug association (triplet, quadruplet). The emergence of immunotherapy allowed new combinations principally based on monoclonal anti-CD38 antibodies for these patients. Still, the optimal induction treatment has not been found yet. While consolidation is still debated, maintenance treatment is now well acknowledged to prolong survival. Lenalidomide monotherapy is the only drug approved in that setting, but many innovations are expected. Older patients, now logically named not transplant-eligible, also took advantage of these breakthrough innovations as most of the recent drugs have a more acceptable safety profile than previous cytotoxic agents. For this heterogenous subgroup, geriatric assessment has become an essential tool to identify frail patients and provide tailored strategies. At relapse, options are now numerous, especially for patients who were not treated with lenalidomide, or not refractory at least. Concerning lenalidomide refractory patients, approved combinations are lacking, but many trials are ongoing to fill that space. Moreover, innovative therapeutics are increasingly being developed with modern immunotherapy, such as chimeric antigen receptor T-cells (CAR-T cells), bispecific antibodies, or antibody–drug conjugates. For now, these treatments are usually reserved to heavily pre-treated patients with a poor outcome. MM drug classes have tremendously extended from historical alkylating agents to current dominant associations with proteasome inhibitors, immunomodulatory agents, and monoclonal anti-CD38/anti SLAMF7 antibodies. Plus, in only a couple of years, several new classes will enter the MM armamentarium, such as cereblon E3 ligase modulators (CELMoDs), selective inhibitors of nuclear export, and peptide–drug conjugates. Among the questions that will need to be answered in the years to come is the position of these new treatments in the therapeutic strategy, as well as the role of minimal residual disease-driven strategies which will be a key issue to elucidate. Through this review, we chose to enumerate and comment on the most recent advances in MM therapeutics which have undergone major transformations over the past decade.

Background: The treatment revolution of multiple myeloma (MM) with the advent of novel therapies, proteasome inhibitors, immunomodulators and newer drugs lead to increased survival. Clinical characteristics at diagnosis of Long-term survivor (>5 years after the start of treatment) were described; however data regarding the profile of lines of treatment is very limited. The aim of this study was to describe the profiles of response of this population. Methods: The Poitou‐Charentes cancer registry has exhaustively registered incident cases of MM from 2008 to 2010. The follow-up date was December 31st, 2018. Patients (pts) alive after 5 years from the start of first line treatment were considered long-term survivors and their data were collected from their medical files. Three pts profiles were studied, very long responder (VLR) treated with a single line; long responder (LR) treated with [2-3] lines; and advanced (AdMM) [4 lines +[. Smoldering Myeloma, AL amyloidosis, lost to follow-up pts were excluded from the analysis. Results: Among the 396 MM registered, 177 were alive after 5 years, and 158 were included in the study. The mean age was 62.3 +/-11, sex ratio 1.2, 51% IgG, 25% IgA and 20% Light Chain isotype. ISS1 was 42%, 34% ISS2 and 14% ISS3. The median follow-up after the 5-year landmark was 39.9 +/-13 months and 52% pts died during follow-up. Overall, the median number of lines was 2.9 +/-2, 44% had at least one ASCT, 83% received Bortezomib, 72% Lenalidomide, 48% Thalidomide, 22% Pomalidomide, 20% Daratumumab (usually 3 lines+). VLR represented 19%, 27% LR, and 54% AdMM. In VLR group, 43% received a Bortezomib-based regimen (2 or 3 drugs) followed by ASCT, 47% a Melphalan-based regimen plus Thalidomide (MPT) or Bortezomib (MPV). In LR group, first line comprised: 39% Bortezomib-based regimen and ASCT versus 24% MPT and 15% MPV. Second line for LR group: 75% had Lenalidomide single agent or combination, 22% had a Bortezomib-based regimen, 17% had an ASCT. In the LR group, 45% received a third line: 40% Lenalidomide, mostly single agent, 25% a Bortezomib-based regimen and 3% had an ASCT. The AdMM group had a mean of 5.9 +/-1.6 lines (range 4 -11) and 56% of RR patients had at least one ASCT. Conclusion: Approximately 40% of MM were long-term survivors at 5 years from start of therapy in 2010, mainly on the basis of proteasome inhibitors and immunomodulators-based regimens plus use of ASCT. The vast majority of pts reached the 5 years cut-off with [4;+[ lines, and very few pts were real long-term survivors with an early prolonged control of Myeloma. Future perspective will look into 10 years long-term survival, including novel drug developments with the advent of immunotherapy. Disclosures Sabirou: AbbVie: Research Funding. Leleu:Janssen: Honoraria; Amgen: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Oncopeptide: Honoraria; Karyopharm: Honoraria; Merck: Honoraria; BMS: Honoraria.

BACKGROUND: Tunneled central venous catheters (TCVCs) are used in cancer patients for irritant or vesicant infusion such as chemotherapy or antibiotics. However, they can be associated which significant complications. Midline catheters (MCs) are peripheral intravenous access devices that ends in a large peripheral vein, easier to install and which may reduce the need for TCVCs. Therefore, the aim of this study is to assess the rate of adverse outcomes with both kind of catheter, in hospitalized patients for the treatment of acute myeloid leukemia. METHODS: We retrospectively compared the use and outcomes of TCVCs and MCs at our institution between December 2017 and December 2018. Data were collected using electronic medical records. Both devices were used indistinctly among our hospitalized patients for chemotherapy, antibiotics and parenteral nutrition. The following complications were recorded: catheter related bloodstream infection (defined as documented bacteriemia and differential time to positivity pointing to TCVC as main source), local signs of infection (such as erythema or inflammation) at insertion site, thrombosis which required an anticoagulant treatment, extravasation and local bleeding at insertion site. RESULTS: Through this period, 39 TCVCs and 50 MCs were used among 56 different patients. As expected duration of the device was shorter for MCs (mean 24days) as they were ablated on discharge, compared to TCVCs (mean 32.5 days). Median aplasia duration (defined as polymorphonuclear neutrofils count in peripheral blood No extravasations were found in any group. As expected local bleeding was more frequent inTCVCs [6 (15.8%) vs 1 (2%); p=0.039]. Whole complications (infection, thrombosis and bleeding) were more frequent among TCVCs (n=35) than among MCs (n=18) even when reported to the length of the catheter (1.08 complications/day in TCVCs and 0.75 complications/day in MCs). SUMMARY/CONCLUSION: MCs insertion -quick and easy- makes them user-friendly for hematologists and can be safely used among acute leukemia patients. Disclosures Leleu: Oncopeptide: Honoraria; Carsgen: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Sanofi: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Merck: Honoraria; Karyopharm: Honoraria.

// Guillemette Fouquet 1, * , Stephanie Guidez 2, 11, * , Valentine Richez 2 , Anne-Marie Stoppa 3 , Christophe Le Tourneau 4 , Margaret Macro 5 , Cecile Gruchet 2 , Arthur Bobin 2 , Niels Moya 2 , Thomas Syshenko 2 , Florence Sabirou 2 , Anthony Levy 2 , Paul Franques 2 , Helene Gardeney 2 , Lionel Karlin 6 , Lotfi Benboubker 7 , Monia Ouali 10 , Jean-Claude Vedovato 10 , Pierre Ferre 10 , Mariya Pavlyuk 10 , Michel Attal 8 , Thierry Facon 9 and Xavier Leleu 2, 11 1 Institut Imagine, Unite Inserm U1163, Centre National de la Recherche Scientifique CNRS ERL8254, Paris, France 2 Hopital La Miletrie, Centre Hospitalier Universitaire, Poitiers, France 3 Institut Paoli Calmettes, Marseille, France 4 Institut Curie, Paris, France 5 Centre Hospitalier Universitaire, Caen, France 6 Centre Hospitalier Lyon Sud, Lyon, France 7 Centre Hospitalier Universitaire Tours, Tours, France 8 Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France 9 Service des Maladies du Sang, Centre Hospitalier Regional Universitaire, Lille, France 10 Institut de Recherche Pierre Fabre, Toulouse, France 11 Inserm Centre d’Investigation Clinique U1402, Centre Hospitalier Universitaire, Poitiers, France * Co-first author Correspondence to: Xavier Leleu, email: xavier.leleu@chu-poitiers.fr Keywords: multiple myeloma; CXCR4; monoclonal antibody; immunotherapy; homing of tumor cells Received: January 08, 2018 Accepted: March 29, 2018 Published: May 08, 2018 ABSTRACT Purpose: Multiple myeloma (MM) remains an incurable disease as tumor cells ultimately resist to all available drugs. Homing of tumor cells to the bone marrow microenvironment, involving especially the CXCR4/SDF-1 axis, allows them to survive, proliferate and resist to therapy. F50067, a humanized anti-CXCR4 IgG1 antibody, has promising preclinical activity in MM. We present a phase I multicenter escalation study in relapsed/refractory MM (RRMM) to determine the maximum tolerated dose (MTD) for F50067 alone and in combination with lenalidomide and low dose dexamethasone (Len-Dex). Experimental design: 14 end-stage RRMM patients received F50067 single agent ( n = 10) or in combination with Len-Dex ( n = 4). Results: One dose-limiting toxicity was observed, a grade 4 neutropenia lasting more than 7 days in combination arm. MTD could not be established. Thrombocytopenia was observed in 100% and neutropenia in 92.9% of patients with no cases of febrile neutropenia and no severe bleeding or hematoma. Non-hematological adverse events were of mild to moderate severity. Nine patients (6 in single arm and 3 in combination arm) were evaluable for response, with 66.7% overall response rate (≥PR) in combination arm, and 33.3% of disease control (≥SD) in single agent arm. At the time of study termination, 55.6% had progressed. Conclusion: This study suggests that egression of tumor cells to the blood stream can represent a novel therapeutic strategy for MM. However, because of significant hematological toxicity, this study had to be discontinued. Further studies are needed to validate the feasibility of this approach in clinical practice.

8041 Background: Triplet-based Carfilzomib (K), Lenalidomide and Dexamethasone combination (KRd) has led to approval in early RRMM based on ASPIRE International phase 3 study. However, K was used on a twice a week basis at 27mg/m2 and limited to 18 months exposure. We have reported already that KRd on a weekly basis at 56 mg/m2 was active similar to ASPIRE KRd and safe. We report herein the long-term exposure data on KRd weekly given until progression. We aimed to evaluate the efficacy of KRd given on a prolong duration beyond 18months, and to validate the safety profile of continuous exposure to K. Methods: 28 patients were prospectively recruited. Carfilzomib 20/56mg/m2 was administered on days 1,8,15, Lenalidomide 25mg/day was given 21/28 days and Dexamethasone was administered weekly on 28 days cycles until progression. Results: With a median follow-up at start of KRd of 30 months, 50% of patients relapsed and 39% died. 24/28 patients received 1 prior line of treatment. 8/28 patients are still on treatment with duration > 24 month and 6/28 with duration > 30 months. The median number of cycles was 15. ORR and CBR was 85.7% and 89.3%, whom 46% ≥ CR ; with a median DOR of 13 months and 43% having more than 18 months. 6 patients had negative MRD at 10-6 and normalized PET CT. Median of OS is not reached, and the 30 month-expected OS from the start of KRd was 56%. The median PFS and EFS was at 29 months, and the 30 month-expected PFS and EFS was 45%. PFS and EFS being superimposable speaks to that there was no safety concern related to prolonged exposure to K. Only 4 patients stopped KRd for safety issues. Hematologic and non-hematologic adverse events ≥ grade 3 were reported in 16/28 and 10/28 patients. Adverse events ≥ grade 3 seen in ≥10% of patients were neutropenia, thrombocytopenia, vomiting and pyrexia. Of note, 5 patients (18%) were ≥ 65 years old and showed similar data compared to the cohort. Conclusions: KRd weekly is effective and safe to early in RRMM patients, provides improved safety profile to patients allowing treating patients until progression. Further studies are warranted to confirm this data on a larger early RRMM population and validate the concept of long duration of treatment using Carfilzomib combination.

Background. Triplet-based lenalidomide plus dexamethasone combinations have become the new standard of care for early relapse and refractory multiple myeloma (RRMM), including carfilzomib plus lenalidomide/dexamethasone (KRd) based on ASPIRE phase 3 data. In ASPIRE, and as per the marketing authorization, carfilzomib is given twice a week at 20/27mg/m² on days 1, 2, 8, 9, 15, 16 of a 28 days based cycle. In parallel, ENDEAVOR, a second carfilzomib plus dexamethasone phase 3 study validated that carfilzomib 20/56mg/m² twice weekly was safe in early RRMM. We hypothesized that KRd on a weekly basis, with 3 visits per cycle but using a more intense dosing at 56mg/m², rather than 6 visits at 27mg/m² at hospital, was far less inconvenient to patients.The aim of this study was to evaluate the efficacy and toxicity of carfilzomib weekly plus lenalidomide/dexamethasone regimen in patients treated for early RRMM. Methods. 28 patients were treated with KRd weekly regimen. Patients received carfilzomib plus lenalidomide/dexamethasone in 28-day cycles until disease progression or until occurrence of unacceptable toxic effects. Carfilzomib was administered as a 30-minute infusion on days 1,8,15 (starting dose, 20mg/m2 on day 1 of cycle 1; target dose, 56mg/m2 thereafter). Lenalidomide (25mg) was given on days 1 through 21. Dexamethasone (40mg) was administered on days 1, 8, 15, 22. All assessments were made according to IMWG. Results. The median age was 64 years (45 - 80) with 14% older than 70 years, sex ratio M/F 1.3 and ISS disease stage 2 or 3 in 39%. Patients had received a median of 1 (1 - 3) previous lines of therapy including proteasome inhibitors (100%) and immunomodulatory drugs (43%). All but 2 patients had disease that relapsed to the last line of therapy. With a median follow up of 8 months, 3 patients (11%) relapsed, and one patient died. The median number of KRd cycles administered was 6.5 (1 - 12). Overall response rate was 93%, with 89% ≥VGPR and 61% ≥CR. The mean time to a response was 1.6 months. The median TTP and OS at 12 months were 89% and 95%, respectively. 29% of patients have discontinued treatment, with solely 50% due to adverse events. Hematologic adverse events ≥ grade 3 were reported in 57% and non hematologic adverse events ≥ grade 3 in 36%. Adverse events resulted in a reduction of carfilzomib dose in 11% of patients and a reduction of the lenalidomide dose in 7% of patients. No patient died related to adverse events. Overall, adverse events ≥ grade 3 seen in ≥10% of patients were neutropenia, thrombocytopenia, vomiting and pyrexia. No patient experienced any severe cardiovascular adverse event, including cardiac failure or any severe cardiac issues or thromboembolic events. One patient required an increase of antihypertensive treatment, and resumed Carfilzomib. Conclusion. KRd weekly at 20/56mg/m2 is effective and safe to early RRMM patients. Further studies are warranted to confirm this data on a larger MM population. Furthermore, analysis of long-term outcome is needed on our studied population. Disclosures Leleu: Novartis: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Pierre Fabre: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees.

Introduction. The pronostic of Chronic hepatitis C (Hep C) has transformed towards cure in recent years with the advent of the antiviral treatment by SOFOSBUZIR (400mg/j) and DACLATASVIR (60mg/j) during 11 weeks usually turning HepC into a complete response (undetectable HCV viral load) or with HARVONI (LEDIPASVIR 90mg and SOFOSBUVIR 400mg) during 12 weeks. In parallel, Multiple Myeloma is a known hematological malignancy characterized with a very severe immuno deficiency status particularly of regards to hypogammaglobulinemia, but also recurrent short period of neutropenia, and often lymphopenia, induced by the various treatments available in the armamentarium of Myeloma. One treatment carries certainly the greatest risk of maximizing the global immunodepression of patients with Multiple Myeloma, that is the intensification using autologous transplantation conditionned with high dose melphalan (ASCT). Studies have demonstrated that the vaccination status of patients with Myeloma was severely impaired and that patients could develop infections particularly in the context of the autologous transplantation. We sought to study whether cured Hep C might relapse in patients with Myeloma while treated with induction, autologous transplantation and post transplant treatment phases. Method. We have reviewed 2 cases of MM plus Hep C homogeneously treated on a transplant eligible schema for MM and also treated using the most advanced cure for Hep C treatments. The 2 patients had a VTd- ASCT-VTd for MM treatment. The 2 patients were of genotype 4 Hep C, with the following viral loads, 1 966 055 UI/ml and 7 907 720/ml with normal hepatic enzymes. Results. AGE, sex ratio male, ISS-R was 1 and 3 (b2m elevated plus elevated LDH) respectively. None of the patients was diagnosed with either plasmablastic features, adverse cytogenetic (t(4 ;14) or del17p), PCL or EMD. MM Response prior to ASCT at completion of Induction was CR and PR, respectively. The 2 patients had undetectable viral loads prior to undergo ASCT. Interestingly, we noticed a relapse for one patient 1 month after ASCT (viral load 471 680 UI/ml), the second patient being pending at this timepoint. For the first patient in relapse for Hep C, a second Hep C treatment was started with VIEKIRAX and RIBAVIRINE during 12 weeks allowing the patient to enter again into complete response for Hep C. One year after this second treatment there is no relapse for HCV infection and for multiple myeloma. Conclusion. Autologous stem cell transplantation induces a major immunosuppression increasing the risk for HCV cure treatment failure. We have looked a tour series of patients and already identified one case with such issue, and possibly a second case to come. This data question on the need to use the Hep C cure treatment PRIOR to ASCT in patients with MM given the risk the cost issue and the risk of failure. This data question also the ability of the Hep C cure treatment to be given post ASCT with possibly a greater chance of success. This data must be confirmed on a larger international effort. Disclosures Leleu: Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Background. Pomalidomide in association with dexamethasone is approved for RRMM in 3rd line and beyond based on the MM-003 multicenter international phase 3 study that demonstrated greater efficacy for Pomalidomide plus dexamethasone over high dose dexamethasone. However, MM-003 mainly recruited advanced RRMM with a median of 5 prior lines. Few data is available regarding real life Pomalidomide-based treatment in 3rd and 4th line RRMM. The aim of this study was to study efficacy and safety of Pomalidomide-based treatment in 3rd and 4th line RRMM. Methods. We studied 108 consecutive RRMM treated with Pomalidomide-based treatment in 3rd and 4th line in a multicenter-based study. All assessment made according to IMWG. Results. The median age was 62.5 (range, 30-86), with 36% older than 65 years, sex ratio M/F 1.25 and ISS disease stage 2 or 3 in 58%. 100% were exposed to bortezomib and refractory to Lenalidomide. 52 patients (48%) had pomalidomide-based therapy as 3rd, and 56 (52%) as 4th line. 73% of patients received a double-based therapy (Pomalidomide plus Dexamethasone) and 27% received a triple based therapy (Pomalidomide, Cyclophosphamide and Dexamethasone). Overall ORR was 55%, with 20% ≥VGPR including 5% CR, and was not statistically different in 3rd versus 4th line, and with PCd versus Pd, although the former was always better. With a median f-up of 45 months, overall 77% and 49% had relapsed and died, respectively, with significantly less in benefit to combination and 3rd line compared to Pd and 4th line (p=0.020). The median PFS was 6 (CI95% 2.3;9.6) and 9 (5.5;12.5) months in 3rd and 4th line (p=0.04), and 6 (CI95% 2.8;9.2) and 12 (8.5;15.5) months in Pd and PCd (p=0.04), respectively. Interestingly, the estimated 3 years PFS for 3rd line and PCd was 34% and 32% respectively, greatly superior to 4th line and Pd, 13% and 18%, respectively. Similarly, the median OS from start of Pomalidomide was not reached in 3rd and in PCd lines versus 23months (5;49), (p=0.04), and 32 months (5;-) for 4th line and Pd use, respectively. Pomalidomide was never permanently discontinued for safety issues, but 30 (28% of patients had to reduced pomalidomide dose, 25% to N-1 that is 3mg/d and 3% at N-2 that is 2mg/d. Expectedly, more patients (increased by 10%) had to reduce pomalidomide dose in 4th line compared to 3rd line, although it was not statistically significant, but not with PCd versus Pd. Indeed Cyclophosphamide but not pomalidomide is reduced in modified in dose or scheme when facing safety issues. No patient died related to adverse events. AEs leading to pomalidomide-based modification in schema included hematological in 40% and non hematological AEs in 12% of patients. Overall, the most common adverse events grade 3 or 4 were neutropenia (22%), anemia (11%), thrombocytopenia (7%) and infectious disease (5%). Conclusion. Pomalidomide-based therapy demonstrates efficacy in the real life with a manageable safety profile. We demonstrate herein that early use and combination improves MM on pomalidomide in the real life. Further prospective studies are warranted to confirm this data on a larger MM population. Disclosures Hulin: Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Perrot:Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; Celgene: Honoraria. Macro:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress. Laribi:Hospira: Other: Grant; Amgen: Other: Personal fees; Novartis: Other: Grant and personal fees; Gilead: Other: Personal fees; Roche: Other: Grant; Takeda: Other: Grant and personal fees; Sandoz: Other: Grant; Teva: Other: Grant. Leleu:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.