Abstract: Immunomodulatory drugs (IMiDs) are associated with an increased risk of venous thromboembolism (VTE) in multiple myeloma (MM) patients. We designed MELISSE, a multicentre prospective observational study, to evaluate VTE incidence and identify risk factors in IMiDstreated MM. Our objective was to determine the real-life practice of VTE prophylaxis strategy. A total of 524 MM patients were included, and we planned to collect information at baseline, at four and at 12 months, on MM therapy, on VTE risk factors and management. VTE incidence was 7% (n=31), including 2.5% pulmonary embolism (PE) (n=11), similar at four or 12 months. VTE was observed at all risk assessment levels, although the increased risk assessment level correlated to a lower rate of VTE, maybe due to the implemented thromboprophylaxis strategy. VTE occurred in 7% on aspirin vs 3% on lowmolecular- weight heparin (LMWH) prophylaxis, and none on vitamin K antagonists (VKA). New risk factors for VTE in IMiDs-treated MM were identified. In conclusion, VTE prophylaxis is compulsory in IMiDstreated MM, based on individualised VTE risk assessment. Anticoagulation prophylaxis with LMWH should clearly be prioritised in MM patients with high VTE risk, along with VKA. Further prospective studies will identify most relevant VTE risk factors in IMiDs-treated MM to select accurately which MM patients should receive LMWH prophylaxis and for which duration to optimise VTE risk reduction.

Abstract: Abstract 1169 Background and objectives Immune thrombocytopenia (ITP) is thought to result from an autoimmune mechanism, and some case-reports have suggested that immunizations could be involved and trigger the autoimmune process. This prospective multicenter case-control study investigated for the first time associations between ITP and vaccination in adults, particularly between ITP and influenza vaccinations. Methods Over a three year period, a network of 15 physicians from hematology and internal medicine referral centers across France recruited newly diagnosed cases of primary ITP in patients aged over 15 years fulfilling the ITP standardized criteria of the American Society of Hematology. Recruiting physicians completed standardized forms for each patient and every patient underwent a standardized 1 hour-interview focused on previous medications and vaccinations in the last 12 months. Incident ITP cases were compared to sex and age-matched controls selected and recruited from general practice settings, also from the same geographically areas of France. The method of referent recruitment has been described elsewhere (Grimaldi-Bensouda et al. 2010 Pharmacoepidemiol Drug Saf 2010;19(6):591–5). Controls were also interviewed in the same standardized way as cases. Cases and control were compared in respect of various descriptive factors and potential risk factors for ITP. Written or other confirmation of vaccinations was sought from both the patient and his/her physician. The time window defining exposure to vaccines was 12 months before the index date. In secondary analysis, the most prevalent vaccines in adults were analyzed. Results Two hundred and twenty four cases fulfilling the inclusion criteria and 4412 were included in the study. Seventy eight of the 224 cases (34.8%) and 1566 of 4412 controls (35.5%) received a vaccination within this time window [adjusted odds ratio 0.97, 95% confidence interval 0.70–1.33]. Twenty percent of the cases and 26% of controls received an influenza vaccine [adjusted odds ratio 0.66, 95% confidence interval 0.45–0.98] . Other prevalent vaccines in adult are currently under study. Conclusions This systematic case-control design is well-suited to study rare disorders such as ITP and few such studies have been conducted. Another advantage was the minimization of recall bias because questions about vaccinations were included in a standardized interview focusing on exposure to all medications. When all vaccines were considered, we found no association between vaccination and the incidence of ITP in either crude or adjusted analyses. Moreover, cases were less likely than controls to have been vaccinated against influenza in the 12 months before the index date. Disclosures: Grimaldi-Bensouda: LA-SER: Employment; INSERM: I was the recipient of a research fellowship from the INSERM (French National Institute for Health and Medical Research) at the time of the study. Leighton:LA-SER Europe Ltd: Employment. Aubrun:LA-SER Europe Ltd: Employment. Abenhaim:LA-SER Europe Ltd: I'm a stock owner and chairman of LA-SER, the company conducting the study.

Abstract: Background Peripheral T-cell lymphoma (PTCL) is a heterogeneous and accounts for approximately 10% of all lymphomas. Outcome of relapse/refractory (R/R) PTCL is poor with median progression-free survival (PFS) and overall survival (OS) of 3 and 6 months in the absence of stem-cell transplantation (SCT). [Mak, JCO, 2013]. Brentuximab vedotin (BV) monotherapy is approved for R/R systemic anaplastic large cell-lymphoma (ALCL) based on 86% overall response rate (ORR) and 57% complete remission (CR). [Pro, JCO, 2012] . In other CD30-positive (CD30+) R/R PTCL, the ORR of BV is 41%. Gemcitabine (G) used as monotherapy in control arm in the randomized phase 3 LUMIERE trial, provided ORR and CR rates of 35 and 22% respectively. [O'Connor, JCO, 2019]. Considering these results we designed a phase 2 study for R/R CD30+ PTCL combining G and BV with the primary end point to increase the ORR by 15%, compared to G monotherapy. Patients (pts) and Methods: Pts with histologically confirmed CD30+ (≥5%) PTCL who failed or were refractory to 1-3 prior lines of systemic therapy, with measurable disease and ECOG performance status & lt; 3 were eligible. Pts received an induction of 4 cycles of G-BV (28-days cycles; G: 1000 mg/m² at D1 and D15 plus BV: 1.8 mg/kg at D8). Pts with CR or partial remission (PR) and non-eligible for SCT, received BV maintenance 1.8 mg/kg at D1 (21-days cycles) up to 12 cycles. The primary endpoint was the ORR (CR + PR) according to Lugano criteria based on CT-scan. Secondary objectives included tolerance and safety, DOR, PFS, OS and impact of BV maintenance. Eligible pts were censored at time of SCT. (NCT03496779). Results: From April 2018 to October 2019, 71 pts were included. Pathology central review according to WHO 2017 criteria, so far available for 50 patients, confirmed angioimmunoblastic T-cell lymphoma (AITL) (22 ; 31%); nodal PTCL-TFH (5 ; 7%); PTCL-NOS (5 ; 7%); ALK- ALCL (10 ; 14.1%) ; ALK+ ALCL (4 ; 5.6%), Enteropathy associated T-cell lymphoma (EATL) (2 ; 2.8%); unclassified PTCL (2 ; 2.8%). There were 47 male and 24 female with a median age of 66 years (20-79) and 17 pts were & gt; 75 years. Median time from diagnosis to enrolment was 9.4 months (range, 6-21). Sixty-five pts (91.6%) presented with stage III-IV. The number of prior lines of therapy were 1 (57 pts), 2 (11 pts) or 3 (3 pts), all pts had received previous CHOP-like chemotherapy, 11 pts previous autologous SCT, 5 pts epigenetic modifiers and 39.4% were refractory to their last line of treatment prior to inclusion. The cut-off date of this analysis was 01/31/2020. The 4 cycles of G-BV induction were completed in 45 pts (63%). The reasons for early discontinuation were progression (21 pts), death (3 pts) or adverse event (2 pts). In intention-to-treat analysis, the ORR at the end of induction (EOI) was 47.9% including CR (14 pts; 19.7%), PR (20 pts; 28.2%). PET performed in all patients reaching EOI showed overall and complete metabolic responses in 45.1 and 23.9%, respectively. During G-BV induction 58 pts (81.7%) had at least one G & gt; 3 adverse event (AE) including neutropenia (67.2%), thrombopenia (17.2%), infections (15.5%), peripheral neuropathy (PN) (5.2%) and cardiac event (5.2%). Overall PN of any grade was recorded in 8/71 patients (11%) during G-BV induction and caused BV withdrawal in one case. Among the 34 responding pts after EOI, 27 pts began BV maintenance and 7 pts remain on maintenance at cut-off date. Eight pts were removed from the study due to SCT eligibility, either after the 4 GBV induction (4 pts) or after 1 or 2 maintenance BV cycles (4 pts). With a median follow-up (FU) of 9.5 (0.5-19.4) months, median PFS is 4.5 months (95%CI [3.5 - 10]) and median OS is 12 months (95%CI [8.6 - NR] ). Among the 34 patients in PR/CR after induction, the duration of response (DOR) is 12.8 months (95%CI [10.3 - NR]). At last FU were recorded 32 deaths. Disease status at time of death was PD (25 pts), CR (1 pt) NE or missing (6 pts). Conclusion: The addition of BV to G increases the overall response rate by 15% in the treatment of R/R CD30+ PTCL. OS data are encouraging for this overall R/R patient population but PFS is overall short and a longer FU is mandatory. Especially the DOR of pts achieving CR or PR after 4 cycles of G-BV exceeds 1 year on BV maintenance. This combination is generally well tolerated and this study suggests that G-BV combination could be an interesting alternative for R/R CD30+ PTCL. Disclosures Tournilhac: Janssen: Consultancy, Honoraria, Other: Travel grant; INNATE Pharma: Consultancy, Honoraria; GILEAD: Consultancy, Honoraria, Other: Travel Grant; ABBVIE: Consultancy, Honoraria, Other: Travle grant; Takeda: Consultancy, Honoraria, Other: Travel grant. Laribi:novartis: Honoraria, Research Funding; amgen: Research Funding; abbvie: Honoraria, Research Funding; takeda: Research Funding. Ysebaert:AbbVie: Consultancy; Roche: Consultancy; Janssen: Consultancy. Guidez:BMS: Honoraria; TAKEDA: Honoraria; Service Hématologie et Thérapie cellulaire CHU POITIERS: Current Employment; AMGEN: Honoraria; CELGENE: Honoraria; JANSEN: Honoraria. Le Gouill:Loxo Oncology at Lilly: Consultancy; Roche Genentech, Janssen-Cilag and Abbvie, Celgene, Jazz pharmaceutical, Gilead-kite, Loxo, Daiichi-Sankyo and Servier: Honoraria. André:Celgene: Other, Research Funding; Takeda: Consultancy; Bristol-Myers-Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Karyopharm: Consultancy; Gilead: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Consultancy, Research Funding; Amgen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Johnson & Johnson: Research Funding; CHU UCL Namur, site Godinne, Yvoir, Belgium: Current Employment; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Abbvie: Consultancy; Seattle Genetics: Consultancy. Dupuis:Henri Mondor University Hospital Creteil France: Current Employment. Thieblemont:Roche, Amgen, Kyte Gilead, Celgene, Abbvie, Novartis, Cellectis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Roche, Hospita: Research Funding; Cellectis: Speakers Bureau. Bachy:Beigene: Membership on an entity's Board of Directors or advisory committees; Roche, Gilead: Consultancy; Amgen: Research Funding; Roche, Celgene, Amgen, Janssen, Gilead, Novartis, Sanofi: Honoraria. Morschhauser:Celgene: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; F. Hoffmann-La Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Epizyme: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Servier: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Feugier:janssen: Consultancy, Honoraria, Research Funding; gilead: Consultancy, Honoraria, Research Funding; roche: Consultancy, Honoraria, Research Funding; astrazeneca: Consultancy, Honoraria, Research Funding; abbvie: Consultancy, Honoraria, Research Funding. Cartron:F. Hoffmann-La Roche: Consultancy, Honoraria; Abbvie: Honoraria; Jansen: Honoraria; Celgene: Consultancy, Honoraria; Sanofi: Honoraria; Gilead: Honoraria. Camus:ROCHE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); JANSSEN: Honoraria; AMGEN: Honoraria; PFIZER: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Sibon:takeda france: Consultancy. Snauwaert:roche: Other: travel; janssen: Other: travel; abbvie: Other. Delarue:BMS: Other: stock options ; Celgene/BMS: Current Employment. De Leval:Abbvie: Honoraria; Lausanne University Hospital & Lausanne University Institute of Pathology: Current Employment; Roche Diagnostics: Honoraria; Lunaphore Technologies SA: Consultancy, Honoraria. Gaulard:CHU Henri Mondor, Assistance Publique-Hôpitaux de Paris: Current Employment; TAKEDA: Consultancy, Honoraria, Research Funding; INNATE PHARMA: Research Funding; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company).

Abstract: Abstract 809 Background. Immunomodulator drugs (IMiDs) are new and very promising oral agents for initial treatment and for treatment of relapse in Multiple Myeloma (MM); however, IMiDs are also associated with an increased risk of venous thromboembolism (VTE) which necessitates routine prophylaxis. Guidelines (Palumbo et al, Leukemia 2008) have proposed either aspirin or low weight molecular heparin (LWMH) for VTE prophylaxis based on a VTE risk stratification. Controversies remain regarding the best choice of VTE prophylaxis regimen in MM patients treated with IMiDs-based therapy and the criteria for the VTE risk definition. More studies are needed to better determine the criteria required for patients to receive either aspirin or LWMH as VTE prophylaxis. We designed a large multicentre observational study aimed at prospectively evaluating the incidence and risk factors of thromboembolism associated with IMiDs [either lenalidomide (Len) or thalidomide (Thal)] therapy in MM. Method. A total of 519 patients with MM treated with first to third line of therapy were included in this study. Patients were treated with IMiDs-based therapy at entry in the study, and those receiving VTE prophylaxis had to start this prior to start IMiDs (the choice was solely that of the clinician). Patients gave written informed consent according to the declaration of Helsinki. Various patient characteristics were recorded, such as age, sex, criteria of vascular complications, including adjuvant treatment such as EPO, bisphosphonates, radiotherapy, and previous history of either deep venous thrombosis (DVT) or pulmonary embolism (PE), or arterial vascular complications. The physicians were to record the risk of VTE occurrence, breakdown as low, mild and high, based on guidelines and their own appreciation of the risk. Occurrence of any thrombosis event (either venous or arterial) was to be recorded along with the descriptive characteristics of the event, how the event was managed and the outcome of the patient. The data were collected at entry in the study, and then at 4 and 12 months. Results. Out of the 519 patients, 35.66% had Thal-based and 64.34% had Len-based therapy. Overall, median age was 71, with 64.67% 〉 65 years old and sex ratio was 249 male/268 female, similar in the 2 groups (data missing for n=2). One hundred and eighty patients were in first line therapy, 169 in second line therapy and 153 in third line therapy (data missing for n=17). Patients were treated with VTE prophylaxis as follow (data missing for n=8); 293 (57.34%) aspirin, 91 (17.81%) LWMH and 46 (9.00%) vitamin K antagonists. Surprisingly, 81 (15.85%) patients had no VTE prophylaxis. Aspirin was administered in 164 (69.79%) of low risk patients and LWMH in 33 (45.83%) of high risk patients. Investigators recorded 13 (3.65%) VTE at the 3564-months visits currently completed, with 7 DVT, 2 PE and 4 DVT+PE. Of these 13 VTE, 8 patients had aspirin, 1 had LWMH and 4 had no prophylaxis treatment. Of the 13 VTE, 1 patient was considered to have high risk of vascular complication and 12 patients either low or moderate risk, according to guidelines. The occurrence of VTE was unrelated to the regimen-based IMiD therapy and the line of therapy. Conclusion. This study further demonstrates that occurrence of VTE is low in IMiDs-based treated MM patients upon VTE prophylaxis, and that VTE prophylaxis is needed for patients treated with IMiDs-based therapy. However, despite VTE prophylaxis, we observed occurrence of VTE. These results question whether the current guidelines on VTE prophylaxis in MM patients treated with IMiDs-based therapy are accurate. Final results will be proposed with updated results at ASH 2010. Disclosures: Leleu: Celgene: Consultancy, Research Funding; Janssen Cilag: Consultancy, Research Funding; Leo Pharma: Consultancy; Amgen: Consultancy; Chugai: Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Daley:LEO Pharma: Employment. Lamblin:LEO Pharma: Employment. Natta:LEO Pharma: Employment.