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 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: 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.

Abstract: Background. The depth of Hypogammaglobulinemia has been related to adverse prognosis in myeloma for decades, but most importantly, it has been suggested that its recovery following treatment was associated with good outcome and prolonged survival. However, none of the traditional techniques has allowed a precise measurement of isotype-matched (i.e. concentrations of IgGκ in an IgGλ myeloma patient) hypogammaglobulinemia. 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 measure Hypogammaglobulinemia, and potentially replace traditional techniques for the monitoring of patients with myeloma. Materials and methods. 107 (59 IgGκ, 29 IgGλ, 12 IgAκ, 7 IgAλ) myeloma patients 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). For each patient we have measured the clonal isotype HLC level, and the corresponding non-clonal paired isotype HLC level, e.g. for IgAκ myeloma, the IgAλ non-clonal paired isotype. (Normal ranges: IgGκ 3.84-12.07, IgGλ 1.91-6.74 and IgGκ/IgGλ 1.12-3.21; IgAκ 0.57-2.08, IgAλ 0.44-2.04 and IgAκ/IgAλ 0.78-1.94 g/L). Results. Overall, 98 (92%) patients had an abnormal suppressed uninvolved HLC level at baseline with suppression being more common in IgG than IgA patients (95% v 73%, p 〈 0.001), and 94 (87%) at the time the greatest response was reached (IgG 90% 〉 IgA 77%), meaning that the vast majority of patients had not recovered from hypogammaglobulinemia at the time of best response. The median uninvolved IgG and IgA HLC concentrations at baseline were 0.62 and 0.2 g/L respectively (range: 05-6.9; 0.01-5.6). At best, response levels reached were 0.53 and 0.24g/L respectively (0.01-5.6; 0.01-7.4). Interestingly, more patients had recovered in the IFM 2009-02 study compared to the IFM2010-02 study, essentially different in the number of prior lines of therapy (3 and 9, respectively). We then sought to understand the relationship with response to therapy. We noted that very few patients’ hypogammaglobulinemia levels normalized completely, nor did their uninvolved paired isotype HLC levels normalize. However, we found that 55% of responders (IMWG) had improved levels (by at least 20%) of the uninvolved paired isotype HLC compared to 18.5% of the non-responders (p=0.001). Similarly, an improvement of at least 50% in the levels of uninvolved paired isotype HLC was achieved by 35% of responders compared to 13% of non-responders, respectively (p=0.013); an improvement of 75% was reached by 22.5% of responders and 7.4% of non-responders (p=0.028). This data strongly correlated to the depth of response, since, for example, 75% of patients in VGPR or better had improved levels of uninvolved paired isotype HLC by 50% at the time of greatest response, compared to 31% for PR and 13% for SD (p=0.005). Similar correlations were seen for 20% (p 〈 0.0001) and 75% (p=0.16) recoveries. Conclusion. The mechanism of immunosuppression in myeloma patients is poorly understood. Here we have shown for the first time that isotype-matched hypogammaglobulinemia correlates to depth of response. Hypogammaglobulinemia is important to assess not only because of its greater risk of infectious complications, often severe in myeloma, but also as it plays a predictive role in occurrence of response and more importantly depth of response. Future studies are needed to unravel the relationship between debulking of tumor cells and correction of hypogammaglobulinemia; in other words, is repopulating of the marrow with normal B cells associated to better outcome, and how does this affect the homeostasis of the bone marrow in its ability to support tumour cells. Disclosures Stoppa: Celgene Jansen: Honoraria. Marit:Celgene, Janssen: Congress expenses Other.

Abstract: Combination of pomalidomide with dexamethasone is highly active and can salvage end stage myeloma refractory to lenalidomide and bortezomib. Current data suggest pomalidomide 4 mg/day on days 1 to 21 per 28-days cycle with dexmethasone should be studied in future phase 3 trials.

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: Abstract 859 Method: This study was addressed to patients with MM who were symptomatic and progressive following at least two cycles of lenalidomide and two cycles of bortezomib (either separately or in combination). Patients must have had at best a stable disease as per IMWG response criteria with the last course of bortezomib and lenalidomide, including refractory pts to bortezomib and lenalidomide (progression on therapy or within 60 days of stopping either regimen). The primary objective was to determine response rate (PR and better) to pomalidomide and dexamethasone using IMWG response criteria. The secondary objectives were to separately determine the response and safety profiles in the 2 dose-regimen modalities of pomalidomide. The time to response, response duration, time to disease progression and overall survival in both arms with regards to cytogenetic of the bone marrow tumour plasma cells were collected. The response and FISH cytogenetic analysis were assessed centrally in Lille and Nantes, France. Pomalidomide was given orally either 4 mg daily on days 1–21 of each 28-days (arm A) or continuously on days 1–28 of each 28-days (arm B). Dexamethasone was given orally at 40 mg daily on days 1, 8, 15 and 22 of each cycle to all patients. All patients received prophylaxis against venous thromboembolism. A first safety analysis was planned when 6 patients were treated within each arm, and the DMC declared both 2 arms safe for further enrolment. A second analysis was planned when 17 patients were randomized to each arm, and the 2 arms were declared promising as we observed at least 4 responses per arm based on a two stage Simon design with comparable incidence of serious adverse events between the 2 arms. Results: Eighty three patients (56 male and 27 female) were enrolled between August first and June first, 43 in arm A and 40 in arm B, respectively. The median age was 54 years (range, 36–78). The median time from diagnosis to enrolment was 55 months (range 11–227) in arm A and 76 (30-281) in arm B. All patients had loss of 17p and t(4;14) cytogenetic abnormalities studied on bone marrow plasma cells. As of August first, the median follow-up was 119 days. The median number of cycles administered was 4 in either arm. Overall, 40 and 36 patients were evaluable for response evaluation in arm A and B, respectively. In arm A, 12 (30%) patients had PR and better, including 3 VGPR, and 21 (52%) had stable disease. In arm B, 17 (47%) patients had PR and better, including 1 VGPR, and 15 (41%) had stable disease. The median duration of response was 77 and 89 days in arm A and B, respectively. Twenty three (57%) and 22 (61%) patients remained progression free, and 5 patients have died in either arm, respectively. Toxicity (at least possibly related to treatment) consisted primarily of myelosuppression in both arms. The occurrence of neuropathy was not observed nor worsening of pre-existing neuropathy. No thromboembolic events have occurred. Conclusion: Pomalidomide and dexamethasone is active and well tolerated in this heavily pre-treated population of lenalidomide and bortezomib-refractory MM patients. This study provides further evidence that pomalidomide has no-cross resistance with lenalidomide and suggests that it can provide benefit for patients who have relapsed after other novel therapies. Updated results will be provided at ASH 2010. Disclosures: Leleu: Celgene: Consultancy, Research Funding; Janssen Cilag: Consultancy, Research Funding; Leo Pharma: Consultancy; Amgen: Consultancy; Chugai: Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Attal:celgene: Consultancy, Research Funding; johnson and johnson: Consultancy, Research Funding. Facon:celgene: Consultancy, Research Funding; johnson and johnson: Consultancy.

Abstract: Abstract 812FN2 On behalf of IFM (Intergroupe Francophone du Myélome) Background. The interim analysis of this phase 2 randomized open label trial was presented at ASH last year. It aimed to determine the impact of the combination of pomalidomide (oral 4 mg daily) and dexamethasone (oral 40 mg weekly) in pts characterized with advanced myeloma (MM) following lenalidomide and bortezomib. The response rate (ORR, PR and better), and the median PFS were similar in the 2 arms, pomalidomide on days 1–21 vs. 1–28 of each 28-day cycle. The final analysis of IFM 2009-02 will be fully presented at ASH 2011. We have also studied subgroups characterized with refractory MM, in order to further demonstrate that the combination of pomalidomide and dexamethasone might benefit pts that have progressed after multiple novel agents. Method. This study was addressed to MM pts who had at best a stable disease with the last course of bortezomib and the last course of lenalidomide, or who were refractory to bortezomib and lenalidomide (as per IMWG criteria). The primary objective was ORR (PR and better). The responses were assessed centrally in Lille, and reviewed by an independent committee (all data reported herein are based on the IRC). FISH cytogenetic analysis was performed in Nantes on bone marrow plasma cells. All pts had received prophylaxis against venous thromboembolism. Data are presented for the overall population when there was no difference between the 2 arms. The analysis is performed on ITT. Results. Eighty four pts (57 male and 27 female) were enrolled; 43 in arm 21/28 and 41 in arm 28/28. The median (min-max) age was 60 (42–83) years. The median time from diagnosis to enrolment in IFM 2009-02 was 70.5 months (9–277). The median number of prior lines of therapy was 5 (1–13), and 100% of the pts had received bortezomib and lenalidomide as per protocol, 70% had received alkylating agents and 71% thalidomide. Overall, 21 (37.5%) pts had loss of 17p (n=15) or t(4;14) (n=6). At the cut-off of March 1st 2011 the median follow-up for alive pts was 10.4 months (1.6–14.3), the median number of cycles administered was 8 (1–18) in arm 21/28 and 6 (1–18) in arm 28/28. The ORR was 34.9% in arm 21/28 and 34.1% in arm 28/28, including 4.7% and 7.3% VGPR, respectively. Overall, 40 (47.6%) pts had stable disease (including minor response) and 3 pts reached CR. The median (95%CI) PFS was 6.3 (4.1–9.1) months in either arm, and the median duration of response was 11.4 (3.7–13.6) months and 7.9 (4.0–) months in arm 21/28 and 28/28, respectively. The median PFS was 4.2 (3.3–6.9) months for pts with SD as compared to 12.6 (9.9–14.8) months in pts that had a response. A summary of subgroups characterized with refractory MM is presented in the table below. Survival and toxicity will be updated at ASH 2011. Conclusion. Pomalidomide and dexamethasone is active and well tolerated in these heavily pre-treated MM pts. This study provides further evidence that pomalidomide has no-cross resistance with lenalidomide and suggests that it can provide benefit for pts who have relapsed after other novel therapies. Disclosures: Leleu: LeoPharma: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding; Roche: Research Funding; Amgen: Honoraria; Novartis: Research Funding. Roussel:Celgène: Honoraria; Janssen: Honoraria. Hulin:Celgene: Honoraria; Janssen: Honoraria. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees.