Abstract: Pom-Dex is active and well tolerated in adverse cytogenetic patients with early RRMM, particularly in those with del(17p). Pom-Dex prolonged OS in adverse cytogenetic patients with early RRMM.

Abstract: Background. Lenalidomide plus Dexamethasone is approved at first relapse and beyond in Europe, and has transformed the prognosis of Myeloma in the relapse setting. Lenalidomide plus Dexamethasone is approved until progression, that could last for years, the median PFS in phase 3 studies being at 17 months at first relapse, but many patients eventually reach 5 to 7 years these days. Dexamethasone was showed to enhance lenalidomide-antitumor efficacy and to prolong the progression-free survival. However, long term exposure to dexamethasone is also known to be associated to an array of adverse events. Finally, IMiDs are known to act through immunomodulation a class-based mechanism. It is possible that lenalidomide might show efficacy on the long run without need to dexamethasone use, at least for some patients with myeloma. We sought to study the impact of dexamethasone discontinuation beyond six months and one year, and compare this analysis to patients treated on lenalidomide plus dexamethasone. Method. We have recruited 200 relapse refractory myeloma patients for this study from various IFM centers. The patients were to be older than 18 years old and treated with lenalidomide plus dexamethasone. We sought to study the impact of the various ways to use dexamethasone in the real life, and therefore dexamethasone was given according to physician decision. We identified groups according to dexamethasone given high dose (4 days 160mg total in a raw), given once a week at 40mg (considered standard dose), given at lower dose (considered low dose) and a group that had dexamethasone discontinued. Patients were not allowed to have other type of combination but lenalidomide plus dexamethasone. Result. A total of 200 patients were analyzed, median age of 57 years old (range 25-76). 17,5% patients had renal dysfunction at diagnosis. ISS was 2 for 20% and 3 for 20%. Approximately 10% had either del17p or t(4;14). 7% of patients had previous history of venous thrombosis before the treatment. Response rate, survival, including TTP, PFS, EFS and overall survival will be presented at ASH with updated follow-up. Conclusion. This study aims to investigate the importance of long run and exposure to Dexamethasone in the Lenalidomide-Dexamethasone regimen. We also wished to assess the optimal dose of dexamethasone that could be given to patients with prolonged exposure to lenalidomide plus dexamethasone. Disclosures Arnulf: Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. MACRO:millenium: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees; 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, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Membership on an entity's Board of Directors or advisory committees. Leleu:LeoPharma: Honoraria; Pierre Fabre: Honoraria; BMS: Honoraria; Novartis: Honoraria; TEVA: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Chugai: Honoraria.

Abstract: Background Frontline ASCT is the standard of care for patients with symptomatic NDMM less than 66 years of age. 3-drug combinations are the standard induction regimens prior to ASCT. Consolidation therapy after ASCT is aimed at improving disease control through deepening responses. Maintenance therapy is administered with the objective of prolonging response duration. The all-oral combination of weekly ixazomib plus lenalidomide and dexamethasone (IRd) was recently evaluated in NDMM, was generally well tolerated and appeared active (Kumar et al, Lancet Oncology 2014;13:1503-12). We analyzed the safety and efficacy of the triplet IRd combination prior to, and as consolidation after ASCT followed by ixazomib maintenance in the initial management of MM in patients younger than 66 years in a phase 2 study (NCT01936532). Methods Patients received 3 cycles of induction therapy with Ixazomib 4 mg on days 1, 8 and 15 plus Lenalidomide 25 mg on days 1 through 21 and dexamethasone 40 mg on days 1-8-15 and 22 of a 28-day cycle followed by Melphalan 200 mg/m2 and ASCT. Two months after ASCT, patients received an early consolidation with 2 cycles of IRd identical to induction therapy followed by a late consolidation phase with 6 additional cycles of IR without dexamethasone. One month after the last consolidation cycle, patients received maintenance therapy with Ixazomib single-agent 4 mg on days 1, 8 and 15 of a 28-day cycle, during 12 months. The primary end-point was the complete response (CR) rate after extended consolidation therapy. The secondary objectives were to evaluate the overall response rate (ORR) after induction, after ASCT, after consolidation and after maintenance, to evaluate the safety of induction therapy, the feasibility of extended consolidation, the feasibility of maintenance with Ixazomib, the duration of response, progression-free and overall survival. Responses (central lab, Dr Dejoie, Nantes) were assessed according to the IMWG criteria. Toxicity was evaluated according to NCI CTCAE, version 4.03. Results From 11/2014 to 04/2015, 42 patients (21 males, 21 females, median age 60 years (43-65)) with NDMM were enrolled in 10 centers from IFM. ISS was 1 in 12 cases (29%), 2 in 23 cases (54%) and 3 in 7 patients (17%), respectively. Adverse cytogenetics (17p deletion, and/or t(4;14); central lab, Dr Avet-Loiseau) was observed in 8 patients (19%). Induction with IRd was very well tolerated. Out of 120 cycles administered for 42 patients, only 13 cases of non-hematologic grade 3-4 toxicities were reported: infections (8 cases), abdominal pain (2), atrial fibrillation (1), thrombosis (1), and DRESS syndrome leading to study withdrawal (1). No renal or liver toxicity was reported. No cardiac failure and no ischemic heart disease was documented. No grade 3-4 peripheral neuropathy was described. Response rates increased at each step of the strategy. Following 3 induction cycles of IRd, the ORR was 81%, including 12% CR plus 24% very good partial response (VGPR), and 2 patients progressed (5%). Following ASCT, the VGPR rate or better was 78% including 38% CR. Following consolidation (early 2 cycles + extended 6 cycles), the VGPR rate or better was 80% including 44% CR. The feasibility of the consolidation phase with IRd (2 cycles) and IR (6 cycles) was excellent: 34 / 37 patients who started consolidation completed the 8 planned cycles (3 discontinuations: 2 patient decisions, 1 progression to plasma cell leukemia). 34/42 patients (81%) were able to receive maintenance therapy with Ixazomib following extended consolidation. Results of maintenance and of minimal residual disease evaluation will be presented during the meeting. At the cut-off date of June 30 2016, with a median follow-up of 16 months, 3 patients / 42 (7%) have progressed, 2 during induction and 1 during consolidation, and 2 (5%) died from progressive disease. Conclusions The all-oral triplet combination IRd administered as induction prior to, and as consolidation following ASCT is safe, convenient, and effective, leading to 80% VGPR and 44% CR before maintenance. Final results on response rates following maintenance and MRD data will be presented during the meeting. Updated results on PFS and OS will also be presented. Disclosures Moreau: takeda: Honoraria; celgene: Honoraria; janssen: Honoraria; BMS: Honoraria; Novartis: Honoraria; Amgen: Honoraria. Hulin:celgene: Honoraria; janssen: Honoraria; takeda: Honoraria. Facon:Millenium/Takeda: Consultancy; Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy; Amgen: Consultancy, Speakers Bureau; Bristol: Consultancy; Janssen: Consultancy, Speakers Bureau; Karyopharm: Consultancy. Leleu:TEVA: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Roussel:celgene: Honoraria; takeda: Honoraria; janssen: Honoraria. avet-Loiseau:takeda: Honoraria; janssen: Honoraria; celgene: Honoraria; amgen: Honoraria. Attal:sanofi: Consultancy; amgen: Consultancy, Research Funding; janssen: Consultancy, Research Funding; celgene: Consultancy, Research Funding.

Abstract: Serum FLC analysis is a more sensitive indicator of disease than urinalysis. Improved sensitivity of serum over urine measurements during monitoring translates into valuable prognostic information.

Abstract: Introduction: Multiple myeloma is one of the most debilitating hematological diseases. Most patients (pts) present with pain, fatigue, and bone lesions, and have a significantly worse health-related quality of life (HRQoL) compared with the general population. The IFM/DFCI 2009 trial demonstrated the clinical benefits of lenalidomide, bortezomib, and dexamethasone (RVd) as induction and consolidation therapy with or without stem cell transplantation (SCT) in newly-diagnosed multiple myeloma (NDMM) pts (Attal M, et al Blood 2015;126:abstract 391). RVd therapy plus SCT was associated with significantly longer progression-free survival in NDMM pts, although this did not translate to an overall survival (OS) benefit. The trial showed that transplant at time of relapse was feasible and not associated with a negative impact on OS. We evaluated changes in HRQoL in these pts, particularly during treatment with RVd to understand the impact of RVd with or without SCT on HRQoL. Methods: The IFM/DFCI 2009 trial was a phase 3, multicenter, randomized, open-label trial in adult pts (N = 700) with NDMM aged ≤ 65 years, and was conducted in France, Belgium, and Switzerland. Pts were randomized (1:1) to: RVd for three 3-week cycles as induction followed by 5 cycles as consolidation (RVd-alone); or RVd for three 3-week cycles as induction therapy followed by SCT and then RVd for consolidation (RVd-SCT). Both arms then received lenalidomide maintenance for 12 months. HRQoL was assessed using the EORTC QoL-Core Questionnaire, QLQ-C30, and the MM module QLQ-MY20. Key domains of interest were global QoL, physical functioning, role functioning, fatigue, and pain (QLQ-C30); and side effects of treatment and disease symptoms (QLQ-MY20). In both arms, assessments were performed on 9 occasions (including at baseline, during induction, consolidation, maintenance, end of treatment, and during follow-up visits). Mean QLQ-C30 scores from the general population (Scott NW, et al. EORTC QoL Group Publications: Brussels; 2008) were used as a benchmark to help interpret the study findings. Results: Compliance rates with the QLQ-C30 were generally high at baseline for both treatment arms (RVd-SCT 88.6%; RVd-alone 90.3%), and remained high at the end of the induction period (RVd-SCT 72%; RVd-alone 76%). Statistically significant (P 〈 0.05) improvements in mean changes from baseline were observed at the end of induction therapy with RVd for both treatment arms in the QLQ-C30 domains of global QoL, physical functioning, role functioning, and pain (not fatigue); and in the QLQ-MY20 domains of disease symptoms except for side effects of treatment (Table). Pts in the RVd-SCT group experienced a significant (P 〈 0.001) and clinically meaningful short-term worsening in most domains following SCT, but scores gradually improved over time. All key domains of interest for QLQ-C30 that were impaired at the time of diagnosis versus the reference values for the general population (male 52%; age range 50-59 years), improved over time in both treatment arms at the end of induction therapy, and continued to improve during consolidation and maintenance periods. Furthermore, these improvements were maintained throughout the rest of the post-treatment follow-up period and were at a level that was close, or equivalent to those experienced by the general population at follow-up visit 2 (Figure). Conclusions: Most functional and symptom domains of HRQoL that were impaired at the time of diagnosis significantly improved during treatment with RVd in SCT-eligible pts with NDMM. This improvement in HRQoL was further increased over the subsequent treatment phases to the level of HRQoL experienced by the general population. This study complements clinical data from the IFM/DFCI 2009 trial, which demonstrated that QoL outcomes for pts could be improved by combination therapy with lenalidomide and bortezomib, thus providing additional support for the use of RVd as induction and consolidation treatment for SCT-eligible pts with NDMM. Furthermore, RVd treatment post-induction seems to improve pt QoL (relative to baseline and measured just before SCT) and could potentially be a strategy to minimize the burden associated with SCT. Further research is warranted to help understand this impact. Disclosures Roussel: Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy. Hebraud:Amgen: Consultancy; Celgene: Consultancy, Other: Lecture fees, Research Funding; Janssen: Consultancy, Other: Lecture fees; travel and accommodation for congress, Research Funding; Takeda: Consultancy; Sanofi: Consultancy. Hulin:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Perrot:Celgene: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Sanofi: Honoraria. Macro:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Janssen: 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; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress. Belhadj:Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Garderet:Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy. Facon:Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Guo:Celgene Corporation: Consultancy. Altincatal:Evidera: Consultancy, Employment. Dhanasiri:Celgene International: Employment, Equity Ownership. Leleu: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; Gilead: 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; Merck: 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; Mundipharma: 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; Janssen: 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; Roche: 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. Moreau:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract: BACKGROUND Triplet regimens bortezomib + lenalidomide + dexamethasone (VRD) and bortezomib + thalidomide + dexamethasone (VTD) are recommended in both European and US guidelines for the treatment (Tx) of transplant-eligible (TE) patients (pts) with newly diagnosed multiple myeloma (NDMM). To date, there are no randomized controlled trials (RCTs) directly comparing them. Therefore, this integrated analysis evaluated VRD vs VTD in TE pts with NDMM. METHODS Published literature was searched for prospective, phase 3 RCTs evaluating VRD or VTD induction (every 3 or 4 weeks) in TE NDMM before autologous stem cell transplant (ASCT). Studies were included if they met pre-defined eligibility criteria, which included having access to pt-level data. The primary objective was noninferiority of the primary endpoint (≥ very good partial response [VGPR] rate post induction. Secondary endpoints included ≥ VGPR rate during induction and post ASCT, and safety. Progression-free survival (PFS) and minimal residual disease (MRD) negativity were exploratory endpoints. Statistical methods for efficacy analyses were based on propensity score (PS), and pts with missing baseline values for the variables used for the PS analyses were excluded. The Cochran-Mantel-Haenszel test, stratified on the stratum based on the quintiles of the PS, was used to estimate the difference of ≥ VGPR rate and 95% CI. RESULTS Four studies met the eligibility criteria: VRD, PETHEMA GEM (GEM)2012 and IFM 2009; VTD, GEM2005 and IFM 2013-04. GEM2005 and GEM2012 were the main studies, as they had a symmetrical design of the induction regimens (six 4-week cycles followed by ASCT). IFM studies were considered supportive since they had a variable number of cycles (3 VRD cycles before ASCT vs 8 VRD cycles in IFM 2009 and 4 VTD cycles before ASCT in IFM 2013-04). Thus, IFM analyses used the subgroup of pts from the VRD induction and consolidation arm of IFM 2009 to compare with the IFM 2013-04 VTD arm. No clinically meaningful differences in baseline characteristics were observed between the VRD and VTD PS-stratified cohorts of the GEM and IFM studies. The integrated analysis met its primary endpoint (noninferiority) and demonstrated a statistically significant and clinically relevant improvement of the ≥ VGPR rate after induction with VRD vs VTD (66.3% vs 51.2%; P = .00281; Figure) in the GEM studies. Non-inferiority results from the IFM studies supported those from GEM, with ≥ VGPR rate by 4 cycles (12 weeks) similar with VRD vs VTD (57.1% vs 56.5%). In the GEM studies, responses deepened during induction. Among the 378 VRD pts who started cycle 6, ≥ VGPR rate increased from 54.5% by 3 cycles of induction to 62.7% by 4 cycles, and to 70.1% by 6 cycles and post induction. Of the 111 VTD pts, these rates were 35.1%, 40.5%, and 55.9%, respectively. Analyses of ≥ VGPR rate post ASCT (74.4% vs 53.5%) and MRD negativity (10-4) rates post induction (46.7% vs 34.9%) and post ASCT (62.4% vs 47.3%) supported the benefit of VRD vs VTD. Safety was as previously reported for these studies. Peripheral neuropathy (PN) is a recognized event that can limit VRD and VTD Tx duration. In the GEM studies, subcutaneous (SC) vs intravenous (IV) administration of bortezomib (BORT) may have contributed to lower rates of PN (grouped term) with VRD vs VTD (grade 3/4, 5.5% vs 15.4%; grade ≥ 2, 20.7% vs 44.6%). Treatment-emergent adverse events (TEAEs) led to dose reduction and study or Tx discontinuation less frequently in the VRD vs VTD cohorts, respectively. In the IFM studies, TEAEs led to dose reduction more frequently and Tx discontinuation less frequently with VRD than with VTD. Grade 3/4 PN (grouped term) was 5.9% vs 15.4%, whereas grade ≥ 2 events were similar (30.3% vs 27.2%), which may reflect BORT administration in these IFM studies (IV for VRD vs SC for VTD, respectively). CONCLUSIONS Induction Tx with VRD had a significantly higher ≥ VGPR rate than VTD when 6 cycles of each Tx were compared in TE NDMM. Deepening responses and MRD negativity further support the benefit of VRD over VTD. TEAEs in the GEM and IFM studies were generally consistent with the known safety profiles of lenalidomide, BORT, thalidomide, and dexamethasone. The TEAEs with the VRD regimen were manageable, and the overall tolerability profile compared well with VTD, with lower rates of PN and TEAEs leading to discontinuation. The integrated analysis supports the favorable benefit-risk profile with VRD over VTD as induction Tx in TE pts with NDMM. Disclosures Rosinol Dachs: Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Oriol:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Rios:Amgen, Celgene, Janssen, and Takeda: Consultancy. Hulin:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Sureda:Merck: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Roche: Honoraria; Sanofi: Honoraria. Mateos:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, 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; GSK: Consultancy, 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; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Macro:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Janssen: 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; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress. San-Miguel:Amgen: Consultancy; Brystol-Myers Squibb: Consultancy; Celgene: Consultancy; Janssen: Consultancy; MSD: Consultancy; Novartis: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees. Belhadj:Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Lahuerta:Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Chen:Celgene Corporation: Employment. Garelik:Celgene Corporation: Employment. Bladé:Celgene: Honoraria; Amgen: Honoraria; Janssen: Honoraria. Moreau:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract: BACKGROUND Real-world data on the use of pomalidomide (POM) for the treatment (Tx) of relapsed/refractory multiple myeloma (RRMM) are limited. The MIROIR study was designed to evaluate POM Tx in routine clinical practice in France. Here, we present results from a prespecified 4-year interim analysis. METHODS MIROIR is a multicenter, observational, ambispective, non-interventional study of POM in routine clinical practice. Adult patients (pts) with MM who initiated POM Tx in France between October 1, 2014, and September 30, 2018, were included. All pts were required to be enrolled in the French IMNOVID® registry. Data were collected from medical records of consenting pts. Key exclusion criteria included previous treatment with POM or simultaneous participation in a clinical trial. The primary endpoint is progression-free survival (PFS) at 6 months. Key secondary endpoints include time to next Tx (TTNT), overall survival (OS), and safety. This study is ongoing; targeted enrollment is 3000 pts (ClinicalTrials.gov, NCT02902900). RESULTS A total of 2099 pts were included in this analysis (median follow-up: 23.3 months; data cutoff: February 1, 2019). Median age was 70.0 years, and 655 pts (31.2%) were aged ≥ 75 years; 1134 pts (54.0%) were male. Median time from start of first-line Tx to POM initiation was 51.4 months. Pts had received a median of 3 prior lines of therapy (range: 0-9), with 914 (43.5%), 644 (30.7%), 312 (14.9%) and 229 pts (10.9%) receiving ≤ 2, 3, 4, and ≥ 5 prior lines, respectively. From 2014 to 2016, the median number of prior lines of therapy before POM initiation was 3, and from 2016 to 2018, the median was 2. Nearly all pts received prior lenalidomide (LEN; 97.0%) and bortezomib (96.7%). POM was initiated at 4 mg/day in 1635 pts (77.9%) overall and in 1216 pts (84.2%) aged 〈 75 years and in 419 pts (64.0%) aged ≥ 75 years. Dexamethasone was prescribed at 20 mg/day and 40 mg/day in 507 (35.1%) and 732 pts (50.7%) aged 〈 75 years and in 405 (61.8%) and 62 pts (9.5%) aged ≥ 75 years. Overall, the 6-month PFS rate was 51.7% (95% CI, 49.4%-54.1%). Other key PFS data in pt subgroups are reported in the Table. In the overall population, median TTNT, 12-month OS rate, and median OS were 10.4 months (95% CI, 9.7-11.2), 70.6% (95% CI, 68.5-72.6), and 24.6 months (95% CI, 22.9-not reached), respectively. Among 1164 pts (55.5%) with ≥ 1 adverse event (AE), the most common AEs were neutropenia (290 pts; 24.9%), infections (263 pts; 22.6%), thrombocytopenia (99 pts; 8.5%), and asthenia (87 pts; 7.5%). POM dose was reduced due to an AE in 20.7% of pts; POM Tx was interrupted or discontinued due to an AE in 36.2% and 15.2% of pts, respectively. CONCLUSIONS The results of this interim analysis confirm the efficacy of POM reported in clinical trials and underscore its role in Tx of RRMM, including after LEN Tx. Median PFS in pts with ≤ 2 prior Tx lines was numerically longer than in pts who had more Tx lines, supporting earlier Tx with POM. PFS outcomes were similar regardless of the duration of LEN Tx ( 〈 or ≥ 6 months) before initiation of POM and whether pts had received LEN or another Tx as their most recent therapy. The latter finding suggests that POM can be used after relapse or resistance to LEN and that there is no need to replace an IMiD agent with another class of treatment. Disclosures Decaux: Celgene Corporation, Janssen, Takeda, Amgen: Honoraria. Macro:Celgene, Janssen, Amgen, Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial Support. Gourgou:Celgene: Employment, Equity Ownership. Lachenal:Celgene: Other: Scientific Comittee's. Stoppa:Celgene: Honoraria. Jaccard:Abbvie: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria. Moreau:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Perrot:jannsen: Honoraria, Membership on an entity's Board of Directors or advisory committees; takeda: Honoraria; Amgen: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Karlin:AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fohrer:Celgene: Consultancy, Honoraria. Leleu:Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Merck: Honoraria; Oncopeptide: Honoraria; Karyopharm: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Hulin:celgene: Consultancy, Honoraria; Janssen, AbbVie, Celgene, Amgen: Honoraria.

Abstract: BACKGROUND Pomalidomide (POM; Imnovid) in combination with low-dose dexamethasone (LoDex) demonstrated a significant improvement in progression-free survival (PFS; median, 4.0 vs 1.9 months; P 〈 .0001) and overall survival (OS; median, 12.7 vs 8.1 months; P = .0285) vs high-dose dexamethasone in a phase 3 study of patients with relapsed/refractory multiple myeloma (RRMM; MM-003; San Miguel et al. Lancet Oncol. 2013;14:1055-1066). This trial led to the European approval of POM + LoDEX in patients with RRMM previously treated with ≥ 2 regimens, including lenalidomide (LEN) and bortezomib (BORT), and who had disease progression on their last therapy. However, data on the use of POM in the real-world setting are limited. The goal of the MIROIR study is to investigate the usage, efficacy, and tolerability of POM in current clinical practice in France. Results from a pre-specified 3-year interim analysis are presented. METHODS MIROIR is a multicenter, non-interventional study of POM in routine clinical practice. Adults (aged ≥ 18 years) with multiple myeloma who initiated POM treatment in France between October 1, 2014, and September 30, 2017, were included (data cutoff, February 1, 2018). All patients were required to be enrolled in the Imnovid registry (a non-interventional post-marketing authorization registry) and to provide consent. Key exclusion criteria included previous treatment with POM or simultaneous participation in a clinical trial. Patients were followed up for ≤ 24 months after treatment initiation. Data were collected from patient medical files. The primary endpoint is PFS at 6 months. PFS is defined as the time from POM treatment initiation to the first progression according to International Myeloma Working Group criteria or death from any cause. Key secondary endpoints include OS, time to next treatment (TTNT), and safety. This study is ongoing; targeted enrollment is 3000 patients (ClinicalTrials.gov, NCT02902900). RESULTS A total of 1581 patients were included in this analysis (median follow-up, 19.1 months). The median age was 69.8 years, and 480 patients (30.4%) were aged ≥ 75 years; 844 patients (53.4%) were male. The median time from first-line treatment to POM initiation was 52.6 months. Patients had received a median of 3 prior lines of therapy (range, 0-9), with 628 (39.7%), 509 (32.2%), and 444 patients (28.1%) receiving ≤ 2, 3, and ≥ 4 prior lines, respectively. The most common prior treatments included BORT (97.3%), LEN (97.0%), melphalan (80.3%), and autologous/allogeneic stem cell transplant (50.0%). POM was prescribed at 4 mg/day in 923 patients (83.8%) aged 〈 75 years and in 300 patients (62.5%) aged ≥ 75 years. Dexamethasone was prescribed at 20 mg/day and 40 mg/day in 382 (34.7%) and 566 patients (51.4%) aged 〈 75 years and at 20 mg/day and 40 mg/day in 287 (59.8%) and 49 patients (10.2%) aged ≥ 75 years. The 6-month PFS rate was 50.5% (95% CI, 47.7%-53.3%). Other key PFS data are reported in the Table. Median TTNT was 9.8 months (95% CI, 9.0-10.6 months). The 12-month OS rate was 68.7% (95% CI, 66.1%-71.0%), with a median OS of 22.4 months (95% CI, 21.0-24.6 months). A total of 233 serious adverse events (AEs) related to POM were reported; 26 (11.2%) were neutropenia, 13 (5.6%) were pancytopenia, and 13 (5.6%) were thrombocytopenia. POM dose was reduced due to an AE in 20.0% of patients; treatment was discontinued or interrupted due to an AE in 14.9% and 35.2% of patients, respectively. Many patients received concomitant treatments and supportive care in the form of thromboprophylaxis (81.2%), antiviral prophylaxis with valacyclovir (63.3%), antibiotic prophylaxis (55.8%), bisphosphonates (20.9%), erythropoietin (20.1%), and granulocyte colony-stimulating factor (8.8%). CONCLUSIONS The results of this interim analysis of the real-world MIROIR study confirm the efficacy of POM reported in clinical trials and underscore its role as a treatment in RRMM. Median PFS was numerically longer in patients who had received only 1 to 2 prior lines of therapy, supporting earlier initiation of POM. The results also indicate that POM is effective in patients whose disease has relapsed or developed resistance to LEN; PFS outcomes were similar regardless of whether patients had received LEN or another treatment as their most recent therapy. This suggests that there is no need to switch from an immunomodulatory agent to another class of treatment after relapse or resistance to LEN. Disclosures Hulin: Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Macro:Janssen: 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; Takeda: 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. Gourgou:Roche: Other: Expertise methodological seminar Force 1 since 2007 and real-life study ; Celgene Corporation: Other: Expertise methodological mirror . Lachenal:Celgene: Other: Scientific Committees . Stoppa:Celgene Corporation: Honoraria. Moreau:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Perrot:Celgene: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Sanofi: Honoraria. Mohty:MaaT Pharma: Consultancy, Honoraria. Karlin:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Fohrer:Celgene: Consultancy, Honoraria. Sylvain:Gilead: Other: scientific advisor board. Leleu:Celgene: Honoraria, Other: steering committee membership ; Janssen: Honoraria, Other; BMS: Honoraria, Other: steering committee membership ; Merk: Honoraria, Other: steering committee membership ; Takeda: Honoraria, Other: steering committee membership ; Amgen: Honoraria, Other: steering committee membership ; Sanofi: Honoraria, Other: steering committee membership steering committee membership ; Novartis: Honoraria, Other: steering committee membership ; Roche: Honoraria; Gilead: Honoraria; Incyte: Honoraria, Other: steering committee membership ; Karyopharm: Honoraria. Decaux:Takeda: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Celgene: Honoraria.

Abstract: Background. The combination of pomalidomide and low-dose dexamethasone (Pom-Dex) has been proven effective and safe in patients with end-stage relapsed/refractory multiple myeloma (RRMM), otherwise characterized by a very poor outcome and short survival of less than a year. However, multiple myeloma remains incurable and relapses are inevitable even with pomalidomide-based regimen. It is thought that patients are back to unmet medical need after pomalidomide exposure, although the outcome after pomalidomide remains unknown. We sought to analyse the line of therapy in RRMM after Pom-Dex treatment, the response to further treatment line and survival post pomalidomide era. Methods. We included 134 patients from the 2 IFM studies (IFM2009-02 in end stage RRMM, n=84, median therapy 5 lines and IFM2010-02 in del17p and/or t(4;14) RRMM, n=50, median therapy 2 lines) treated with Pom-Dex. In both studies, patients received pomalidomide (oral 4mg daily) given either 21 days out of 28 or continuous and dexamethasone (oral 40mg weekly, but 20mg if 〉 75 years old in the IFM 2010-02), given until progression. Overall, 95/135 patients (70%) received further therapy post Pom-Dex, 57/84 (68%) and 38/50 (76%) in IFM2009-02 and IFM2010-02 studies, respectively; the remaining patients had palliative care. Results. As a whole for the 95 patients, the median age was 60 (range 31-82), the M/F ratio was 1.5, t(4;14) was observed in 26/50 (52%) and del17p in 14/47 (30%). The post Pom-Dex regimens were very diverse, and varied significantly across the 2 trials; however, the regimens contained alkylating agents in 54% and 60% of patients in IFM2009-02 and IFM2010-02, respectively. The most prescribed alkylator was cyclophosphamide (60%) in IFM2010-02 while similar prescription of cyclophosphamide and bendamustine was observed in about 40% of patients in the IFM2009-02 study (p=0.032). Alkylating agents were administered primarily in a 3 drugs-based combination (or more) in IFM2010-02, 70%, versus in combination solely to dexamethasone for most patients in IFM2009-02, 60% (p=0.034). Amongst the combinations of alkylating agents, novel agents were considered in 55% versus 17.5% in the 2 studies, as expected considering that IFM2010-02 included patients exposed but not refractory to lenalidomide, while IFM2009-02 recruited essentially patients double refractory to lenalidomide and bortezomib (p 〈 0.0001). Interestingly, in 57% of cases the novel agent used was bortezomib, often associated to thalidomide. When no alkylating agent was used, bortezomib plus dexamethasone, dexamethasone alone, or clinical trials were favoured, the latter in a lesser instance. An intensification was proposed in 8% of patients (n=8), with allogeneic transplantation in 3 patients. 27% and 29% responded to the post Pom-Dex regimen, with an extra 35% and 34% having stable disease in the 2 studies, respectively. With a median follow-up of 49 months (IFM2009-02) and 24 months (IFM2010-02), 77% and 52% of patients have died. The median PFS on Pom-Dex was approximately 5 months (CI95% 2.5;6.5) across the studies, with 20% of patients free of relapse beyond a year, similar to the post Pom-Dex phase, 5 months (2.9;7.0) and 4 months (2.2;5.7) in 2010-02 and 2009-02, with 29% and 13% of patients progression-free beyond one year, respectively. Importantly, the median OS of IFM2009-02 study (end stage RRMM, median 5 lines) for patients that had a post pomalidomide regimen was 20 months (14;26), with 30% of patients beyond 3 years, versus 13 months for the study as a whole (Leleu et al. Blood 2013) including patients considered in palliative care after Pom-Dex was stopped. This difference was not observed in IFM2010-02 to the same extent, in patients treated earlier with Pom-Dex but characterized with poor risk cytogenetic features, del17p and/or t(4;14), median OS of 14 months (9;18) across the 2 subgroups versus a median OS of 12 months and 9.8 months for the 2 subgroups in the study as a whole (Leleu et al. Blood 2015). Conclusion. Pom-Dex changed the paradigm in advanced RRMM with a prolonged PFS that translated into a prolonged OS. Importantly, OS was further improved when patients were offered a post pomalidomide therapy particularly in advanced RRMM with no poor risk cytogenetic features. Future studies might confirm the survival impact of pomalidomide used earlier in the disease course. The IFM2009-02 and 2010-02 trials were conducted with the support of Celgene Disclosures Karlin: BMS: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria. MACRO:celgene: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees. Arnulf:Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Stoppa:Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Legros:BMS: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; ARIAD: Speakers Bureau. Garderet:Bristol-Myers Squibb: Consultancy. Moreau:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Avet-Loiseau:Janssen: Research Funding; Celgene: Research Funding; Takeda: Research Funding. Attal:jansen: Honoraria; celgene: Membership on an entity's Board of Directors or advisory committees. Facon:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Membership on an entity's Board of Directors or advisory committees. Leleu:Pierre Fabre: Honoraria; BMS: Honoraria; Novartis: Honoraria; TEVA: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; LeoPharma: Honoraria; Chugai: Honoraria.

Abstract: High dose chemotherapy plus autologous transplantation (ASCT) is considered a standard of care for newly diagnosed myeloma patients younger than 65 years of age. The high complete response rate (CR) achieved with the triplet combination of immunomodulatory drugs + proteasome inhibitors + dexamethasone has led investigators to propose this strategy upfront without immediate ASCT. The aim of this study was to determine if, in the era of new drugs, ASCT was still required in the initial management of young patients. We conducted a randomized trial comparing conventional dose treatment (RVD arm= 8 cycles of Lenalidomide, Bortezomib and Dexamethasone, plus stem cell mobilization after 3 cycles of RVD utilizing high dose cyclophosphamide and G-CSF) to RVD with ASCT (Transplant arm= 3 induction cycles of RVD, followed by stem cell collection, and then ASCT conditioned with Melphalan 200 mg/m2, followed by 2 cycles of RVD as consolidation). Maintenance treatment with Lenalidomide (10 to 15 mg/d) was used in both arms for one year. In the RVD arm, ASCT was planned at time of relapse. From November 2010 to November 2012, 700 previously untreated French and Belgian patients were equally randomized between arms. Randomization was stratified according to ISS stage (I vs II vs III) and FISH analysis (standard vs high risk = del 17p or t(4;14) or t(14;16)). The primary study end point was progression-free survival (PFS). Two pre-specified interim analysis were to be performed at 33% and 69% of the estimated total number of events. The second interim analysis was performed in June 2015 (346 events= 197 in the RVD arm, 149 in the transplant arm). These results were submitted to an independent data management and safety committee, who recommended completing the trial, and continuing follow-up (without cross over before progression), since the difference in PFS between the 2 groups had reached the pre-specified level of significance for stopping the study. As of June 8, 2015, median follow up was 39 months. All patients had discontinued treatment (completion of planned therapy= 66%, disease progression= 16%, adverse events= 10%). Patient characteristics of each group were similar and no significant differences were found with regard to age (median=58 years), ISS stage (I=233, II=341, III=126), Ig isotype, beta-2-microglobulin (median=3.5 mg/L), and cytogenetics (high risk=90 patients). In the transplant arm, 93% of patients underwent ASCT and 5 toxic deaths occurred during mobilization or in the actual transplant phase (1.4%). ASCT was found to improve PFS (stratified p value for log-rank test 〈 0.0002; HR= 1.5, 95% CI= 1.2-1.9). The 3-year post-randomization PFS rate was 61% in the transplant arm versus 48% in the RVD arm. The PFS benefit observed in the transplant arm was uniform across all the following subgroups: age (≤ or 〉 60 years), sex, Ig isotype (IgG or others), ISS stage (I or II or III), cytogenetics (standard or high risk), and response after the 3 first cycles of RVD (complete response or not). The 3-year post randomization rate of overall survival was extremely high (88%) and similar between the 2 study groups (stratified p value for log rank test=0.25). The complete response rate was significantly higher in the transplant arm compared to the RVD arm: 58% versus 46%, respectively (p 〈 0.01). Forty-one second primary malignancies among 39 patients were recorded (Transplant arm=23, RVD arm=18). In conclusion, these results demonstrate that ASCT should remain a standard of care for young patients with de novo myeloma, and suggest that RVD plus ASCT could be a future reference strategy in this setting. Further follow-up is needed, as the number of deaths is still low in both arms. The parallel US trial, which uses a similar design but importantly administers maintenance Lenalidomide continuously until progression in both arms, is ongoing. Disclosures Attal: celgene: Membership on an entity's Board of Directors or advisory committees; jansen: Honoraria. Hulin:jansen: Membership on an entity's Board of Directors or advisory committees; 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, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Membership on an entity's Board of Directors or advisory committees. Arnulf:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. MACRO:celgene: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees. Garderet:celgene: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees. Roussel:celgene: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees. Avet-Loiseau:celgene: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees; onyx: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Munshi:novartis: Membership on an entity's Board of Directors or advisory committees; onyx: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees. Richardson:Novartis: Membership on an entity's Board of Directors or advisory committees; Millennium Takeda: Membership on an entity's Board of Directors or advisory committees; Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees. Moreau:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees.