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. Protein electrophoresis and immunofixation in the serum (SPEP - SIF) and urine (UPEP – UIF) have been routinely used for decades for characterizing and quantifying the M protein in Multiple Myeloma (MM). However, these techniques are notoriously tarnished with inaccuracy, despite improvements in recent years. The most important breakthrough in the field in recent years was the discovery of the Serum Free Light Chain Assay (sFLC), a routine quantitative and automated assay that measures kappa and lambda sFLC, however this was added to / rather than replaced traditional tests in the diagnostic armamentarium of MM. Recently, a new test quantifying paired clonal and non-clonal immunoglobulins (heavy/light chains HLC i.e. IgGκ/IgGλ) in serum was developed. Here we aim to assess the new HLC assays as tools to replace SPEP / IFE during MM patient monitoring Materials and methods. 110 Myeloma treated with pomalidomide and dexamethasone in two IFM studies (IFM 2009-02 in end stage RRMM and IFM 2010-02 in del17p and t(4;14) RRMM ) were included. The criteria for selection were that patients had measurable intact immunoglobulin myeloma according to IMWG criteria (M spike ≥10g/L), using serum and/or urine protein electrophoresis, with exclusion of patients solely measurable on UPEP and sFLC. All sera were collected centrally before initiation of treatment and sequentially every cycle until progression. Hevylite® (HLC) was measured in the biology laboratory of CHRU of Lille, France and results compared to traditional measurements. Along with SPEP, SIF, UPEP, UIF, and sFLC, we have also measured IgA HLC (IgA k and IgA l) and IgG (IgG k and IgG l) and the corresponding difference (clonal - non clonal) and ratio (clonal/non clonal). Results. Overall, 80% were measurable on SPEP with a median serum level of 31g/L (CI95% 19;42), and the remaining also had UPEP measurable myeloma with a median serum level of 0.66g/24h (CI95% 0.4;1.3). The median involved HLC level was 29.7g/L (CI95% 17.6;43.3), the median involved HLC difference clonal - non clonal was 28.8g/L (CI95% 15.6;42.7), the median involved HLC ratio clonal / non clonal was 51.9 (CI95% 18.3;203.9). Since all patients had a measurable intact immunoglobulin-based disease according to IMWG criteria, we have first confirmed that patients had also a measurable disease by HLC. All patients had an abnormal HLC ratio but one patient, who was measurable with an abnormal IgG L involved HLC test. Approximately 32% of patients had an M-spike below 20g/L and/or an electrophoretic migration in beta region meaning in the range of lack of sensitivity of the techniques used, all of whom had a measurable disease using involved HLC level and/or a measurable HLC ratio. We then sought to study the response rate according to HLC, and for that purpose we applied the exact same criteria as to the sFLC-based response criteria recommended by IMWG (e.g. normal ratio is CR and if abnormal ratio, then 〈 50% reduction in the difference clonal – non clonal is SD, ≥50% - 〈 90% reduction is PR, 〉 90% reduction is VGPR). The ORR in the 2 studies as a whole using traditional measurements was 32%, including 29% PR rate, absence of CR, and 44% had SD (SD and MR). Using HLC, the ORR was 36%, including 26% PR rate and 4.0% CR, and 33% had SD (r² 0.823, p 〈 .0001). Interestingly, 7 patients classified as SD with regular techniques, were progressive disease using HLC, anticipating a progression of Myeloma. Similarly, 5 patients classified as SD with regular techniques, were ≥PR using HLC. Conclusion. HLC is a new routine quantitative and automated assay that measures Immunoglobulin heavy chain/light chain pairs immunoassay, allowing diagnosis, prognosis and precise assessment of the response to treatment and disease progression in all cases with Myeloma treated with pomalidomide and dexamethasone in 2 different clinical trials. Our study indicates that HLC may be used as a replacement for traditional tests and may offer greater sensitivity in some instances. Furthermore, obviating the need for interpretation may standardize assessments of patients during trials. Future studies might confirm this data analysis in larger trials. Disclosures Karlin: Janssen: Honoraria; celgene: Consultancy, Honoraria; Sandoz: Consultancy. Hulin:Celgene: Honoraria. Stoppa:Celgene Jansen: Honoraria. Marit:Celgene, Janssen: Congress expenses Other.

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 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: Background. The IFM2009-02 study was launched in 2009, and randomized 84 patients (pts) with pomalidomide (oral 4 mg daily) and dexamethasone (oral 40 mg weekly) given either 21 days out of 28 or continuous. Whilst the overall median PFS was 4.6 months - this end stage very advanced RRMM population, we observed that 40% of the patients had a prolonged PFS and subsequently OS in the trial. We sought to analyze the characteristics of 58 pts that had more than 3 months of pomalidomide to study the effect of long exposure to Pomalidomide. Method. IFM 2009-02 was a multicentre phase 2 study of pts with RRMM who had at best a stable disease with the last course of bortezomib and of lenalidomide, or who were refractory to bortezomib and lenalidomide (IMWG). This analysis was performed on the ITT population combining data from the 2 study arms. We have analyzed the characteristics of pts according to duration of treatment with pomalidomide and dexamethasone 3 months to one year ( 〈 1 year) or more than one year (≥1 year). Results. 60% and 40% of pts were exposed to pomalidomide for 〈 1 year and ≥1 year, respectively. The ORR for the 〈 1 year group was 43%, the median PFS 4.6 months (CI95% 4;6) with only 6% at 12 months, and the median OS 15 months (4;6) and 65% at 12 months, 40% at 18 months. For the ≥1 year group, the response rate and survival were strikingly different, ORR at 83%, PFS 20.7 months, OS not reached (CI95% 40;-) and 100% at 12 months, 91% at 18 months. Of the pts in the 〈 1 year, 87% have died versus 35% in the ≥1 year group. Of note, death of most pts occurred during the follow up period post pomalidomide therapy , however in a far greater extent for the 〈 1 year group, 96% versus 67%, that could suggest it was more difficult to salvage these pts post pomalidomide. We next sought to identify the characteristics of the 2 groups. Interestingly, the median number of prior lines was similar across groups, 5 (range 1-10), with 89% and 79% of the pts exposed to more than 3 lines and 17% and 22% exposed to more than 6 lines, for the 〈 1 year and ≥1 year groups, respectively. 40% and 48% of pts had Bortezomib as last line, 29% and 43% Lenalidomide, 43% and 26% and alkylating agent. Similarly, 80% and 74% of pts were refractory to Bortezomib, 89% versus 87% to Lenalidomide, 65% versus 75% to alkylating agents, 74% and 87% to the last line of therapy, respectively. 74% and 70% were double refractory (Bortezomib and Lenalidomide) and 60% and 70% were triple refractory (double +last line), respectively. The time from diagnosis to IFM 2009-02 study entry was also similar between cohorts, 5.8 and 6.5 years for 〈 1 year and ≥1 year groups; however with 6% versus 26% of pts, entering the study in less than 3 years since diagnosis. There was no difference in terms of patients characteristics between groups, either patients-based such as gender, age, weight, or myeloma-based characteristics. However, serum beta 2m level was higher at diagnosis in the 〈 1 year compared to the ≥1 year, 54% versus 35%, with a slightly more adverse cytogenetic profile 35% versus 12%, with the limitation that this was not available for all the patients. Presence of plasmacytoma/EMD was also greater in the former group, 20% versus 4%, respectively. It seems that the 〈 1 year had more intrinsic adverse features of the tumor cells compared to the ≥1 year group. There was no clear difference in terms of safety management of pomalidomide and/or dexamethasone, with respect to the daily dose intensity of Pomalidomide (median, 3.0 and 2.9 mg/day), and the relative dose intensity of pomalidomide that was 89% and 84%, respectively; similar to the rate of dose reduction and dose interruption. Conclusion. Pomalidomide and dexamethasone is effective and well tolerated in these heavily pre-treated MM pts refractory to Bortezomib and Lenalidomide, with approximately 40% of the patients having a prolonged exposure to treatment, which translated into a significantly prolonged OS. Our study suggests that patients with more intrinsic adverse features of Myeloma tumor cells could not have prolonged exposure to pomalidomide as they progressed within a year from start of pomalidomide. Future studies should examine optimizing pomalidomide therapy in those patients, such as using multidrug pomalidomide-based combined regimens to prolong exposure to pomalidomide and improve the survival of these patients. Disclosures Karlin: Janssen: Honoraria; celgene: Consultancy, Honoraria; Sandoz: Consultancy. Stoppa:Celgene Jansen: Honoraria.

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: Multiple myeloma with del(17p) and/or t(4;14) are characterized with short survival related to early relapse rate (median TTP 〈 4 months) and rapid development of mechanisms of resistance to multiple agents. Furthermore, RRMM to IMiDs® imunomodulatory agent and proteasome inhibitors (bortezomib) also display a shortened median survival of approximately 9 months. We and others have previously showed that pomalidomide plus low-dose dexamethasone has produced 30% to 40% response rate (ORR, PR and greater) with prolonged duration of response (DOR) and median time to progression (TTP) in RRMM who have progressed after multiple treatment options. However, the median TTP was much shorter 〈 4 months for patients with del17p and/or t(4;14) who have been previously exposed to a median of 5- 6 lines of therapies in those studies. We have designed a phase 2 multicenter, open-label study aimed to determine the efficacy and safety profile of pomalidomide in RRMM patients with del(17p) and/or t(4;14). Method This study enrolled patients with progressive RRMM that were relapsing but not necessarily refractory to lenalidomide (minimum two cycles). Del(17p) and/or t(4;14) was identified centrally by Pr. Avet-Loiseau using FISH on bone marrow plasma cells. The response was evaluated centrally in Lille according to IMWG criteria. The primary objective was to evaluate TTP using pomalidomide plus low-dose dexamethasone in RRMM with del(17p) and/or t(4;14). Pomalidomide was given orally at 4 mg daily on days 1–21 of each 28-days and dexamethasone orally at 40 mg daily on days 1, 8, 15 and 22 of each cycle. Venous thrombotic events (VTE) prophylaxis was mandatory. The primary analysis was conducted on the ITT population. An interim analysis is reported. Results 50 patients (gender ratio 1.5) were enrolled, the median age was 59 yrs (range, 30-80). The median time from diagnosis to enrolment was 3 years (IQ 2-4), 40% had ISS 3, and 60% high beta2m. All patients had loss of 17p (46%) and/or t(4;14) (64%). At entry into the trial, 30% had Hb 〈 10 g/dL, 12% platelet count 〈 100 G/L and 4% neutrophils 〈 1 G/L, 6% had circulating plasma cells and 10% presence of clinically plasmacytomas. The median number of prior lines of therapy was 3 (1-10). All patients had prior exposure to lenalidomide with 84% refractory, 96% had received a proteasome inhibitor with 54% that became refractory; 90% had got an alkylating agent, with 36% became refractory; 76% had an autotransplant and 2% an allotransplant. Overall, 76% were refractory to the last line of therapy prior to study entry. The overall response rate (ORR) was 20% (27% in del17p and 16% in t(4;14)), including 6% 〉 VGPR, and 54% had stable disease. The median duration of response was not reached, but the 6-months event-free survival (EFS) was 54%. With a median follow-up of 5 months (IQ 3-11), 66% have stopped treatment including 76% due to progression of MM, and 38% had died. The median OS for the cohort as a whole is 12 months (CI95% 5;nr), with a 8-months event-free survival rate of 59%. Interestingly, del(17p) patients benefited more from pomalidomide plus low-dose dexamethasone as median OS was not reached, with 63% 8-months OS, while 9 months (4.5;16) for t(4;14). The median TTP for the cohort as a whole is approaching 3 months (2-5), nonetheless longer for del17p, 8 months (3;nr) versus 3 months (2;4) for t(4;14). We then concentrated on RRMM with more than 2 cycles, and found a similar profile with a clear cut benefit for del17p as compared to t(4;14) treated with pomalidomide plus low-dose dexamethasone. Toxicity was manageable in these fragile RRMM patients with 40% of serious adverse events (SAEs) reported related to the studied treatment, 13% of which led to death and 21% to permanent drug discontinuation. An other 48% led to drug dose reduction. No occurrence or worsening of neuropathy was reported, and only 1 pulmonary embolism was noted. Conclusion Pomalidomide plus low dose dexamethasone is active and well tolerated in this RRMM population characterized with high and rapid development of a refractoriness state, particularly with del(17p). This study provides further evidence that IMiD® compound, including pomalidomide is active in patients with adverse FISH cytogenetic and that ongoing triplet-based combination should demonstrate improved response rates and survival in future studies. Updated results will be presented at ASH2013. Disclosures: Leleu: JANSSEN: Honoraria; CELGENE: Honoraria. Off Label Use: Pomalidomide. Karlin:Janssen: Honoraria; Celgene: Export board committee Other, Honoraria. Roussel:JANSSEN: Honoraria; CELGENE: Honoraria. Moreau:JANSSEN: Honoraria, Speakers Bureau; CELGENE: Honoraria, Speakers Bureau. Attal:JANSSEN: Honoraria, Speakers Bureau; CELGENE: Honoraria, Speakers Bureau. Avet-Loiseau:JANSSEN: Honoraria, Speakers Bureau; CELGENE: Honoraria, Speakers Bureau. Facon:JANSSEN: Honoraria, Speakers Bureau; CELGENE: Honoraria, Speakers Bureau.