Abstract: 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/m 2 and limited to 18 months exposure. We have reported already that KRd on a weekly basis at 56 mg/m 2 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/m 2 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.

Abstract: Background Ixazomib (IXA) is an orally-administered proteasome inhibitor approved in Europe in November 2016 for relapsed and/or refractory multiple myeloma (RRMM). It became available in France in May 2017 via a compassionate use program (CUP) and from October 2018 via the classical market access (non-CUP). In addition to pivotal clinical trials, real-world evidence (RWE) is required to evaluate effectiveness and safety in clinical routine practices. A non-interventional study, has been conducting in France to evaluate IXA use in combination with lenalidomide and dexamethasone (IRD) in real life. Methods REMIX is a non-interventional, multicentric study to assess IRD effectiveness and safety, conducted in 59 sites (public and private) in patients with RRMM. IRD was initiated in second line or more during the CUP and afterwards. After inclusion, patients were assessed every 3 months (mo) during 24 mo then every 6 mo as per standard practice. This interim analysis assessed IRD effectiveness (median Progression Free Survival (mPFS), 12 and 24-mo overall survival (OS) rates and tolerance in the CUP patients initiating IXA concomitantly to RD (patients who started lenalidomide more than 6 weeks before IXA were excluded). The analysis was conducted globally and per subgroups (age, number of lines of treatment, frailty as defined by Facon T & al.in Leukemia 2020). The CUP-patient median study follow-up was 17.4 mo for this interim analysis. Results The 198 eligible CUP patients were 47% of males, with a median age of 69 years (26% ≥75y). Out of them, 45% were frail and 7% had renal failure (CrCl ≤30 ml/min). Comorbidities were reported in 64% of patients including diabetes (9%), renal disease (10%), solid tumor (9%). At diagnosis, the cytogenetic risk was standard, high or unknown in respectively 46%, 13% and 41% of patients; 11% presented a plasmacytoma. 41% had multiple or severe bone lesions and 25% peripheral neuropathy. MM was diagnosed at a median of 4 years before IRD initiation. IXA was initiated after one (L2) / two (L3) / three or more lines of treatment (L4+) in respectively 58%, 18% and 24% of patients. Of them, 38% had received lenalidomide during prior line(s), mainly in patients with L3 and L4+ (78%, 65/84) vs L2 (8%, 9/114). The median washout period between lenalidomide discontinuation and IRD start was 18 mo 95%CI [17.6 - 29.6]. The mPFS was 19.2 mo 95%CI [13.3; 21.9] for the CUP cohort. mPFS was 21.5 mo 95%CI [13.3; 21.9] for L2 (104 patients), 17,8 mo 95%CI [12.2; 26.7] for L3 (29 patients) and 5.6 mo 95%CI [4.1; 8.8] for L4+ (38 patients) (c.f. Figure1). mPFS was similar in & lt;75 YO (19.2, mo 95%CI [12.3; 24.8]) and in ≥75 YO patients (19.2 mo, 95%CI [1.7; 21.5] ). In the subgroup with available frailty score (n= 124), mPFS was 21.5 mo 95%CI [12.5; -] in non-frail and 13.3 mo 95%CI [5.6 ; 19.8] ) in frail patients. 12mo and 24mo-OS rates were 84% 95%CI [78%; 89%] and 73% 95%CI [65%; 80%] for the global group. Among the 166 patients with available response according to investigators, overall response rate (ORR) was 68% (66% in & lt;75 YO and 71% in ≥75 YO patients) and very good partial response (VGPR) 35% (38% in & lt;75 YO and 27% in ≥75 YO patients). The 187 followed-up CUP patients received a median of 14 IRD cycles. IXA discontinuation was reported in 50% of patients (n=92), related to AE in 13% of cases (n= 24). Serious adverse events were reported in 34% (n=69), including 14 (7%) patients with SAE considered related to IXA. Most frequent ( & gt;10%) AE were thrombocytopenia (30%), diarrhoea (28%), asthenia (20%), anaemia (18%), neutropenia (15%), nausea (14%) and peripheral neuropathy (10%). Conclusion Few RWE data have been published for IXA use in Europe. In this first interim analysis, estimated mPFS is consistent with MM1 results or data reported in MM1 study (19,2 mo vs 20.6 mo) even though CUP patients in REMIX were globally elder, frailer and more frequently treated in advanced lines (24% of L4+ in REMIX vs 11% of L4 in MM1). Reported adverse events were in line with known safety IXA profile. Figure 1 Disclosures Laribi: abbvie: Honoraria, Research Funding; amgen: Research Funding; novartis: Honoraria, Research Funding; takeda: Research Funding. Vincent:Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Congress support; takeda: Membership on an entity's Board of Directors or advisory committees, Other: Congress support; janssen: Membership on an entity's Board of Directors or advisory committees, Other: Congress support. Hulin:Celgene/Bristol-Myers Squibb, Janssen, GlaxoSmithKline, and Takeda: Honoraria. Macro:sanofi: Honoraria; gsk: Honoraria; janssen: Honoraria, Other: travel accomodation, Research Funding; takeda: Honoraria, Other: travel accomodation, Research Funding. Karlin:Celgene/Bristol-Myers Squibb: Consultancy, 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, Other: Travel support; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Personal fees; Sanofi: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees. Texier:Kappa Santé: Other: employee of the CRO in charge of REMIX. Chouaid:pfizer: Honoraria, Research Funding; GSK: Honoraria, Research Funding; novartis: Honoraria, Research Funding; pfizer: Honoraria, Research Funding; takeda: Honoraria, Research Funding; bms: Honoraria, Research Funding; msd: Honoraria, Research Funding; astra zeneca: Consultancy, Honoraria, Research Funding; amgen: Consultancy, Honoraria, Research Funding; roche: Consultancy, Honoraria, Research Funding. Leleu:GSK: Honoraria; Amgen: Honoraria; BMS-celgene: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Oncopeptide: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Merck: Honoraria; Novartis: Honoraria; AbbVie: Honoraria; Karyopharm: Honoraria.

Abstract: 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.

Abstract: Background : Bacterial infections (BI) are a major cause of morbidity and mortality in patients treated for hematological malignancies, especially those with acute myeloblastic leukemia or receiving allogeneic hematopoietic stem cell transplantation. Despite severe neutropenia and prolonged treatment with corticosteroids, there are little published data on BI during induction chemotherapy in adults with acute lymphoblastic leukemia (ALL). Between 2006 and 2014, 787 adult patients were included in the GRAALL-2005 study, a prospective, randomized and multicenter phase III trial for patients newly diagnosed patients with Philadelphia chromosome-negative B-cell precursor (BCP) or T-cell ALL. We retrospectively reviewed the occurrence of BI during induction treatment in these patients. Patients and Methods: The GRAALL-2005 study evaluated the value of hyperfractionated cyclophosphamide in the whole study population and of rituximab in patients with CD20+ BCP-ALL. All patients received a 5-drug induction therapy with corticosteroids (prednisone) for 21 days, associated with vincristine, daunorubicin, cyclophosphamide and L-asparaginase. A broad-spectrum antibiotic treatment effective on Gram-negative and positive germs was recommended when the neutrophil count was less than 0.5 G/L. Pneumocystis prophylaxis was made by trimethoprim/sulfamethoxazole or pentamidine. Results: During induction chemotherapy, 270 of the 787 patients (34.3%) experienced a total of 376 BI episodes (1.4 BI episodes per patient). The BI incidence rate was higher in the subgroup of patients combining hyperfractionated cyclophosphamide and rituximab as compared to those who received standard-dose cyclophosphamide and no rituximab (40.7% versus 29.5%; p=0.098). The median time from the first day of induction therapy to BI diagnosis was 10 days (range, 7-14). The infection was considered as serious in 58 patients, with a diagnosis of septic shocks in 57. Forty-one patients were transferred in intensive care unit. At 50 days after induction initiation, 22 patients had died from BI: 8.1% of patients with BI and 2.8% of all patients. Bloodstream was the most common site (82.7%), followed by gastrointestinal tract (6.5%) and lungs (6.5%). In less than 2% of cases, skin and soft tissues, central venous catheter, or urinary tract was concerned. Infections with Gram-positive cocci predominated as the etiology of microbiologically documented infections (46.9%), more specifically coagulase-negative Staphylococci. E. coli and Pseudomonas species were the most common Gram-negative organisms (40.5%). The patients received a median number of 3 antibiotics. The first-line was a monotherapy in 57% of cases, with the predominant use of betalactam. In one-third of the cases, it was betalactam in combination with aminoglycoside or glycopeptide. More than 2 antibiotics were prescribed in 12% of cases. Conclusion: Induction chemotherapy in adults with ALL is associated with a high incidence of bacterial infections and a significant related mortality. To our knowledge, this report is the only large adult ALL study dealing with bacterial infectious complications during induction chemotherapy. Despite an intensely myelosuppressive chemotherapy regimen, the infection-related mortality seems to be lower than that reported during induction in acute myeloid leukemia. Predictive risk factors for bacterial infections have to be analyzed, as well as prophylactic/empirical antibiotic strategies in order to improve care for this subset of patients. Disclosures No relevant conflicts of interest to declare.

Abstract: Multiple myeloma (MM) is a haematological cancer characterized by a malignant plasma cell infiltration restricted to the bone marrow (BM). Bcl-B protein is the last anti-apoptotic member of the Bcl-2 family to be discovered and is mainly expressed in B lymphocytes and human plasma cells. However, its pathophysiologic role is still unknown. Our team has generated a transgenic mouse model (Eμ-Bcl-B) where Bcl-B protein expression is restricted to the B cell compartment; Eμ-Bcl-B mice develop with age a lymphoproliferative syndrome recapitulating all of the human MM characteristics. Following these promising results, we focused our attention on the potential role of Bcl-B protein in the pathogenesis of MM to designate this anti-apoptotic protein as a prognostic marker and eventually as a new therapeutic target. BM samples were collected with the support of the internal medicine and clinical hematology departments of Nice CHU to study the expression of Bcl-B protein in the plasma cell population. BM extracts were separated into 2 parts: 1) 3 millions cells were used to measure Bcl-B expression level by flow cytometry. For this purpose, we performed successively an intracellular (Bcl-B) and an extracellular (CD138+ plasma cells) staining. For each patient, results were expressed as the percentage of plasma cells (CD138+) expressing intracellular Bcl-B marker. 2) The remaining cells were subjected to CD138 positive magnetic sorting to isolate plasma cells. The quantification of Bcl-B protein in the plasma cells was performed in this case by semi-quantitative Western blot experiment. Between March 2011 and July 2015, 68 BM extracts were analyzed. Among these patients, the median age was 70 years with a sex ratio 1:1. We studied the expression of Bcl-B in 3 healthy individuals, 21 MGUS (Monoclonal Gammopathy of Undetermined Significance) patients, 15 MM patients at diagnosis and 1 patient suffering plasma cell leukemia. In addition we analyzed 7 samples from MM patients treated with first-line therapies and 21 samples from relapsed MM patients. Using flow cytometry, we determined that the average expression of the Bcl-B protein was 3.66% within the plasma cell population of healthy individuals, 4.56% in MGUS patients, 53.56% in newly diagnosed MM patients and 99% in untreated plasma cell leukemia. In addition, the average expression of Bcl-B protein in the plasma cell population was 9.14% in MM patients treated with first-line therapies and 50.33% in relapsed MM patients. Western Blot experiments performed with CD138+ sorted plasma cells revealed an overexpression of Bcl-B protein in newly diagnosis and relapsed MM patients and in patients suffering plasma cell leukemia. MGUS and MM patients treated with first-line therapies revealed a low expression of Bcl-B. In conclusion, thanks to the BM patients samples collected with the support of the internal medicine and clinical hematology departments of the Nice CHU, we showed overexpression of the anti-apoptotic Bcl-B protein in MM patients at diagnosis or after relapse compared to patients with MGUS. Importantly, the Bcl-B protein was undetectable in MM patients that respond to first-line therapies. Altogether, these results, combined with those obtained from our transgenic mice Eμ-Bcl-B model, suggest that Bcl-B protein could be a new diagnostic marker for MM and a pertinent tool to predict the quality of response treatment. Disclosures No relevant conflicts of interest to declare.

Abstract: Multiple myeloma (MM) is rare in young patients, especially before age 40 years at diagnosis, representing & lt;2% of all patients with MM. Little is known about the disease characteristics and prognosis of these patients. In this study, we examined 214 patients diagnosed with MM at age ≤40 years over 15 years, in the era of modern treatments. Among them, 189 patients had symptomatic MM. Disease characteristics were similar to older patients: 35% had anemia, 17% had renal impairment, and 13% had hypercalcemia. The staging was ISS-1 in 52.4%, ISS-2 in 27.5%, and ISS-3 in 20.1%. Overall, 18% of patients had high-risk cytogenetics [del 17p and/or t(4;14)]. Ninety percent of patients received intensive chemotherapy followed by autologous stem cell transplant, and 25% of patients had allogeneic stem cell transplant predominantly at time of relapse. The median follow-up was 76 months, the estimated median overall survival was 14.5 years, and the median progression free-survival was 41 months. In multivariate analysis, bone lesions (hazard ratio [HR] , 3.95; P = .01), high ISS score (HR, 2.14; P = .03), and high-risk cytogenetics (HR, 4.54; P & lt; .0001) were significant risk factors for poor outcomes. Among predefined time-dependent covariables, onset of progression (HR, 13.2; P & lt; .0001) significantly shortened overall survival. At 5 years, relative survival compared with same age- and sex-matched individuals was 83.5%, and estimated standardized mortality ratio was 69.9 (95% confidence interval, 52.7-91.1), confirming that MM dramatically shortens the survival of young patients despite an extended survival after diagnosis.

Abstract: BACKGROUND: Real-world data can provide important information on the safety profile for recommended treatment options, but these data are collected infrequently. The ongoing post-authorization safety study (PASS) MM-034 (NCT03106324) is a prospective non-interventional study in patients (pts) with newly diagnosed multiple myeloma (NDMM) who are transplant ineligible. This study allows for the collection of robust safety data for currently recommended regimens for the management of these pts. Global guidelines recommend lenalidomide (LEN) regimens, such as LEN plus dexamethasone (DEX; Rd) and LEN plus bortezomib (BORT) plus DEX (Vd), and BORT regimens, including BORT plus melphalan plus prednisone (VMP). METHODS: Transplant-ineligible adult pts with NDMM initiating therapy in centers throughout Europe are being enrolled in the ongoing MM-034 trial. Pts receiving any first-line regimen are eligible, but the decision for which treatment regimen will be used must be made prior to study inclusion. The primary endpoint is the incidence of cardiovascular events. Secondary endpoints include the incidence of renal impairment, infections, and second primary malignancies. In this analysis, the safety profiles of Rd, Vd, and VMP were compared. RESULTS: As of April 12, 2019, 145 Rd, 53 Vd, and 83 VMP pts were enrolled in the study (evaluable cohort). At the time of data cutoff, treatment was ongoing in 64.8% of Rd pts, 41.5% of Vd pts, and 61.4% of VMP pts. Median age was 79 years in Rd pts and 75 years in both Vd and VMP pts. The proportion of pts with ISS stage III disease was higher in the Vd group (24.8% Rd vs 32.1% Vd vs 24.1% VMP), and more pts in the VMP group were male (49.7% Rd vs 58.5% Vd vs 65.1% VMP). Adverse events (AEs) of all grades confirmed the expected side effects. Any-grade neutropenia occurred in 7.6%, 11.3%, and 13.3% of Rd, Vd, and VMP pts, respectively, and thrombocytopenia occurred in 6.2%, 5.7%, and 12.0%, respectively. However, any-grade febrile neutropenia was seen only in the VMP group, at 2.4%, but not in the other 2 groups. Any-grade polyneuropathy was reported in 1.4% of Rd pts, but in 18.9% of Vd pts and 19.3% of VMP pts. Any-grade infections of all kinds occurred in 28.3% of Rd pts, 41.5% of Vd pts, and 20.5% of VMP pts, with pneumonia in 3.4%, 11.3%, and 2.4% of Rd, Vd, and VMP pts, respectively. Any-grade thrombosis was reported in 4.8% of Rd pts and 3.8% of Vd pts and in no VMP pts. Grade 3/4 AEs occurred in 42.8% of Rd pts, 52.8% of Vd pts, and 43.4% of VMP pts. Grade 3/4 neutropenia was reported in 4.8%, 9.4%, and 8.4% of Rd, Vd, and VMP pts, respectively, and thrombocytopenia in 2.8%, 0%, and 8.4%, respectively. Grade 3/4 infections were lower in Rd pts (6.9% vs 24.5% Vd and 12.0% VMP); pneumonia, the most important of these, was reported in 0.7%, 5.7%, and 2.4% of Rd, Vd, and VMP pts, respectively. Grade 3/4 peripheral neuropathy was not seen in the Rd group; however, it was reported in 3.8% of Vd pts and 2.4% of VMP pts. Grade 3/4 venous thrombosis was reported in only 0.7% of Rd pts, with no events reported in the Vd and VMP groups. CONCLUSIONS: The results from this analysis, along with those from a previous analysis of cardiovascular events in the LEN-treated and non-LEN treated cohorts of pts from the European PASS MM-034 study (De Stefano, EHA 2019), provide real-world evidence for the safety profile of Rd as first-line therapy and support the role of Rd in the treatment of pts with NDMM who are transplant ineligible. Disclosures Cavo: celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; amgen: 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; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; novartis: Honoraria; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Tromp:Janssen: Other: Grant. Dhanasiri:Celgene Corporation: Employment, Equity Ownership. Kueenburg:Celgene: Consultancy. Rosettani:Celgene International: Employment. Martin:Celgene: Employment. Pozzi:Celgene: Consultancy. Bacon:Celgene: Employment, Equity Ownership. Gamberi:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Front-line treatment (of any type) was at the discretion of the investigator.

Abstract: In July 2004 in Europe, radioimmunotherapy (RIT) with Yttrium-90 Ibritumomab Tiuxetan ((90)Y-IT) obtained marketing authorization (MA) for follicular lymphoma (FL) in consolidation treatment in front line or relapse after rituximab treatment. Additional results also showed the potential interest of high-dose ((90)Y-IT) in monotherapy or in combination with intensive chemotherapy with autologous or allogeneic hematopoietic stem cell transplantation. Due to its particular toxicity profile (extended cytopenia and high rate of oral mucositis), the use of RIT in unselected patients is still debated. The aim of this retrospective cohort study was to evaluate the toxicity and efficacy of (90)Y-IT) in unselected consecutive adult patients treated for CD20+ B-type lymphoma. Between January 2013 and December 2014, 102 patients at 25 Francophone centers were treated with at least one injection of (90)Y-IT. Median age was 62 years (range 32-87) and 36% were female. Sixty-one percent of patients had a low-grade B lymphoma. More than 80% of patients presented an advanced stage with bone marrow involvement in 25% of cases. ECOG performance status was 〈 2 for 94 (92%) patients and 72 (78%) patients had a prognostic score 〉 1. Nearly two thirds of diffuse large B-cell lymphomas (DLBCL) were GC-like. About half of the patients (51%) were treated with ((90)Y-IT) combined with high-dose BEAM chemotherapy (carmustine, etoposide, cytarabine and melphalan) or BeEAM (bendamustine, etoposide, cytarabine and melphalan) followed by autologous stem cell transplantation (autoSCT). Median prior therapies was 1 (range 0-3). Eight (8%) patients were treated with ((90)Y-IT) combined with intensive chemotherapy (fludarabine, busulfan) and allogeneic stem cell transplantation (alloSCT): median prior therapies was 2 (range 1-4). Forty-two (41%) patients were treated with RIT in monotherapy: median prior therapies was 1 (range 0-3). Among the 42 patients treated with ((90)Y-IT) as consolidation, 6 (14%) did not receive chemotherapy before administration of RIT, 8 (19%) received R bendamustine, 12 (29%) RCHOP, 14 (33%) R DHAox and 2 (5%) received RFC regimen before RIT. The median time between diagnosis and first administration of ((90)Y-IT) was 22 months (range 1-281) and the median time between the last treatment received and the start of RIT regimen was 1 month (range 0-75). In the autoSCT group, ((90)Y-IT) combined with BEAM or BeEAM, the post-RIT evaluation showed 45 (86%) complete responses (CR), 2 (4%) partial responses (PR), 4 (8%) stable disease (SD) and 1 (2%) progression (PG). The median time to onset of grade 3 or 4 anemia, thrombopenia and neutropenia was, respectively, 6 (range 1-90), 8 (range 3-90) and 10 days (range 6-90). Grade 3 or 4 oral mucositis occurred in 29 patients (56%). Interestingly, among patients treated with Z-Beam associated with amifostine (n=6), only one patient suffered from severe oral mucositis (17%). In the group of patients who underwent alloSCT, ((90)Y-IT) injection combined with fludarabine and busulfan, the post-RIT evaluation showed 4 (50%) CR, 1 (12.5%) PR, 1 (12.5%) SD and 2 (25%) PG. The median time to onset of grade 3 or 4 anemia, thrombopenia and neutropenia was, 12 (range 10-35), 15 (range 11-240) and 23 days (range 15-48), respectively. Severe oral mucositis (grade 3-4) occurred in 3 patients (37%). In the group of patients who underwent consolidation treatment, ((90)Y-IT) injection in monotherapy, the post-RIT evaluation showed 25 (60%) CR, 9 (21%) PR and 8 (19%) PG. The median time to onset of grade 3-4 anemia, thrombopenia and neutropenia was 70 (range 4-150), 80 (range 6-100) and 45 days (range 6-120), respectively. Grade 3/4 oral mucositis occurred in 1 patient (2%). The median follow-up time was 11 months (range 1-30). Median progression-free survival (PFS) and overall survival (OS) were 9 months (range 1-30) and 11 months (range 1-120), respectively. These results confirmed, on a large retrospective series of unselected patients, the safety and efficacy of ((90)Y-IT) administered in monotherapy or in combination with intensive chemotherapy with autologous or allogeneic hematopoietic stem cell transplantation, without increased toxicity. For autologous bone marrow transplant, the use of amisfostine could lower the high-grade mucositis rate. However, further analysis of long-term outcome criteria such as PFS, OS and toxicities will be of interest in this series of patients. Disclosures Off Label Use: In this study, Yttrium-90 Ibritumomab Tiuxetan is administred in monotherapy for follicular lymphoma (MA) and in monotherapy or combination with intensive chemotherapy with autologous or allogeneic hematopoietic stem cell transplantation for CD20+ B-type lymphoma..