Lust, John A.

Abstract We investigated whether interleukin-1β (IL-1β) is differentially expressed in plasma cells from monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patients because IL-1β appears to play a major role in the development of lytic bone lesions, the major clinical feature distinguishing MGUS from myeloma. In situ hybridization (ISH) for IL-1β was performed using bone marrow aspirates from 51 MM, 7 smoldering MM, 21 MGUS, and 5 normal control samples. Using the ISH technique IL-1β mRNA was detectable in the plasma cells from 49 of 51 patients with active myeloma and 7 of 7 patients with smoldering myeloma. In contrast, 5 of 21 patients with MGUS and 0 of 5 normal controls had detectable IL-1β message. Bone lesions were present in 40 of the 51 MM patients analyzed, and all 40 patients had IL-1β mRNA by ISH. These results show that greater than 95% of MM patients but less than 25% of MGUS patients are positive for IL-1β production. In the future, continued follow-up of IL-1β positive and negative MGUS patients should determine whether aberrant expression of plasma cell IL-1β is predictive of those MGUS patients that will eventually progress to active myeloma.

Abstract Eukaryotic translation initiation factor 5A (eIF5A) has been implicated in the regulation of cell proliferation, apoptosis, and inflammation, and is the only known protein to be modified by hypusination. Hypusinated eIF5A, the predominant form of eIF5A in cancer cells, is involved in cell survival and activation of inflammatory pathways. In contrast, accumulation of the unhypusinated form of eIF5A is associated with apoptosis and mutants of eIF5A that cannot be hypusinated (e.g. eIF5AK50R) are pro-apoptotic. SNS01-T was designed to treat B-cell cancers and consists of two active components: a plasmid DNA expressing the pro-apoptotic eIF5AK50R under the control of a B cell-specific promoter, and an siRNA against an untranslated region of native eIF5A mRNA. When these two components are combined with linear polyethyleneimine (PEI), the nucleic acids are condensed into nanoparticles for protection from degradation in the blood and enhanced cellular delivery. The mode of action of SNS01-T is siRNA-mediated inhibition of hypusinated eIF5A and simultaneous over-expression of pro-apoptotic eIF5AK50R to induce cell death. In vitro cell studies and in vivo xenograft studies have demonstrated the efficacy of this approach. The safety and tolerability of intravenous administration of SNS01-T is being investigated in a first-in-human Phase1b/2a study in patients with relapsed or refractory multiple myeloma (MM), mantle cell lymphoma (MCL) or diffuse large B cell lymphoma (DLBCL). Eligible patients are being enrolled sequentially into four cohorts at increasing doses. Each patient receives an intravenous infusion of SNS01-T twice weekly for 6 consecutive weeks. Eligible patients must have been diagnosed with MM according to IMWG criteria, or with MCL or DLBCL with histologic confirmation. Patients also must have measurable disease, have relapsed or refractory disease after two or more prior treatment regimens, have a life expectancy of at least 3 months, and not be eligible to receive any other standard therapy known to extend life expectancy. The primary objective is to evaluate the safety and tolerability of multiple escalating doses of SNS01-T. Secondary objectives include analysis of pharmacokinetics, immunogenicity, pro-inflammatory cytokines, and therapeutic efficacy. The required 3 patients per cohort have completed the dosing schedule in cohorts 1 and 2 from a total of 10 patients enrolled (9 patients with MM and 1 with DLBCL). Of the ten patients enrolled, four completed the full treatment period, two did not complete dosing but were evaluable for safety, and four (three in cohort 1 and one in cohort 2) discontinued treatment after fewer than 8 doses and were not evaluable. There were no drug-related serious adverse events or dose limiting toxicities in either cohort 1 or 2. In cohort 1 (0.0125 mg/kg SNS01-T), two of three evaluable patients did not progress on treatment and were considered stable at week 3 and week 6, the end of the dosing regimen. The third patient progressed after receiving 10 of the 12 doses and was evaluable for safety. In cohort 2 (0.05 mg/kg), 3 patients (2 with MM and 1 with DLBCL) were evaluable for safety. Stabilization of serum monoclonal protein levels was observed in one MM patient of cohort 2. Two patients (1 with MM and 1 with DLBCL) progressed after receiving 8 of the 12 doses and were evaluable for safety. Results from ongoing pharmacokinetic studies, immunogenicity studies, and quantification of pro-inflammatory cytokines will be discussed. The planned dose levels for the third and fourth groups are 0.2 and 0.375 mg/kg, respectively. The results to date of this first-in-human clinical trial indicate that SNS01-T can be administered safely and the MTD has not yet been reached (Clinical Trials.gov Identifier: NCT01435720). Disclosures: Barranco: Senesco Technologies: Consultancy. Usmani:Celgene, Onyx, Millenium: Consultancy, Research Funding, Speakers Bureau. van Rhee:Jansen&Jansen: Research Funding. Thompson:Senesco Technologies: Consultancy, Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Taylor:Senesco Technologies: stock options Other. Dondero:Senesco Technologies: Employment. Browne:Senesco Technologies Inc.: Employment, Equity Ownership, Membership on an entity’s Board of Directors or advisory committees. Siegel:Celgene, Millenium, Onyx (same for all): Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau.

Abstract Abstract 2887 Introduction: Cardiac involvement is the major cause of death in patients with immunoglobulin light chain amyloidosis (AL). Detection of cardiac involvement and risk stratification has been facilitated by cardiac biomarkers like troponin T (cTnT) and N-terminal brain natriuretic peptide (NT-proBNP). A novel high sensitivity cTnT (hs-cTnT) assay has been developed, and we evaluated its diagnostic use with three questions in mind: 1) How do the cTnT and hs-cTnT perform in the AL amyloid staging system? 2) Does higher sensitivity add significant additional value in terms of prognosticating outcomes for patients with AL amyloidosis? 3) Can the current AL amyloidosis staging system be further improved upon? Methods: Stored serum samples (-20°C) from 224 pts with AL were analyzed for concentrations of hsTnT, TnT, and NT-proBNP on the E170 Modular analyzer (Roche Diagnostics, Penzberg, Germany). 99th percentile reference limits were <0.014 and <0.010 mcg/L for hsTnT and TnT, respectively. Results: Median values for hsTnT, TnT, and NT-proBNP were 38 ng/L (range 0–075.4), 0.017 mcg/L (<0.0–0.904), and 1230 ng/L (0–32, 226), respectively. The correlation coefficient between hsTnT and TnT was 0.972. Those classified by echocardiographic parameters as having (n=143) or not having (n=81) cardiac involvement had TnT concentrations of 0.04 and 0.01 mcg/L and hsTnT levels of 52.2 and 15.6 ng/L, respectively. The direct numeric result from the hs-cTnT result CANNOT merely be substituted for a cTnT result in the Mayo AL staging system since 14% of patients would be misclassified. The performance of the receiver operation curve derived hs-cTnT cut-point of 54 ng/L is a slight improvement over the direct substitution of 35 ng/L if replacement of one assay for another is required. An alternate staging option using hs-cTnT alone—using the two thresholds14 ng/L and 54 ng/L (figure)—performs as well as either the original Mayo AL staging system or a derivative system incorporating hs-cTnT with respective relative risks of death (95%CI) of 3.6 (2.3, 5.7), 3.8 (2.5, 5.9), and 3.3 (2.2, .50). On multivariate analysis, our newly described alternate 3 level, hs-cTnT alone staging system is independent of other factors including period of diagnosis, type of therapy, and NT-proBNP value, the last of which dropped out of the model. Alternate models using NT-proBNP and cTnT were explored, but none performed better than the original staging system or the new hs-cTnT system. Conclusion: The direct numeric result from the hs-cTnT result cannot merely be substituted for a cTnT result in the Mayo amyloid staging system. Consideration could be made for AL staging systems using hs-cTnT alone and relegating the NT-proBNP for measuring cardiac response. Disclosures: Jaffe: Roche: Consultancy.

Abstract 5079 Introduction: IgD monoclonal proteins are rare. They are not seen as a MGUS and are present in 1% to 2% of patients with myeloma. In light chain amyloidosis (AL), IgD monoclonal proteins are rare. When an IgD protein is found, amyloidosis is often omitted from the differential diagnosis. An IgD protein in amyloidosis has been reported in single cases but never as a patient series. We report IgD AL in 53. Patients & Methods: Clinical and demographic data for patients were retrieved from the patient records. Factors of interest were compared between patients who did and did not have an IgD protein. Results: Among 3,955 patients with AL amyloidosis seen, 53 patients (1.3%) had a serum IgD monoclonal protein. (Table 1) A serum monoclonal protein peak was visible on SPE in only 14, and only 5 had an M spike greater than 1 g/dL. On immunofixation of the serum, the IgD light chain was k in 11, λ in 35, and uncertain in 6; 1 patient had a biclonal D λ and G k protein. A urine monoclonal protein was detected in 43 of 51 patients; urinary immunofixation detected a λ light chain in 33 and a k light chain in 10. Biopsy of tissues showed amyloid deposits in the bone marrow in 47% and in the fat aspirate in 73%. Six patients (age 47–63 years) underwent autologous SCT. Four had renal & two had cardiac AL. All 6 had hematologic PR, 4 CR, and 4 had organ response. One patient had relapse of disease and is now on dialysis, and another had relapse and is alive with salvage chemotherapy. One patient had disease relapse and died of progressive GI amyloidosis at 22 months. The other 5 are alive at a median of 68 months (range, 7.5–83.5 months). We compared the 53 patients with IgD amyloidosis with 144 patients with non-IgD amyloidosis. (Table 2) Findings that were significantly different between groups included a lower frequency of renal amyloidosis (P=.005) and a lower prevalence of cardiac amyloidosis (P=.047). There was a higher serum albumin level (P=.04) related to the lower level of proteinuria. No difference in survival was seen between the groups. (Figure). Variables that might affect survival—liver size, performance status, septal thickness, serum creatinine level, and β2-microglobulin level—were not different between groups. Conclusions: IgD AL patients have a lower frequency of renal involvement and possibly also of cardiac involvement. The overall survival of these patients does not appear to be different from that of patients who have AL associated with another monoclonal protein. IgD monoclonal proteins are so closely linked to the diagnosis of multiple myeloma in the mind of a clinician that the possibility of amyloidosis may be overlooked. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 2868 Introduction: Improvement in renal parameters is fundamental for the assessment of organ response to treatment in immunoglobulin light chain amyloidosis (AL). Renal response, defined as a >50% reduction in proteinuria with <25% decrease in renal function, is associated with superior overall survival (OS); however, a systematic study of the interplay of proteinuria, creatinine, and free light chain has not been performed. The intent of this study is to better understand the components of the renal response criteria. Methods: Patients who underwent autologous stem cell transplantation from 1995 to 2010 were eligible for this retrospective analysis if they had > 1 year of follow-up and a baseline 24 hour urine protein > 1 g/d. Those who were dialysis dependent or died before 1 year were excluded as not evaluable for renal response. Results: Of the 435 patients screened, 152 met criteria. On univariate analysis, >50% proteinuria reduction (p < 0.001), serum free light chain (sFLC) reduction by >50% (p = 0.002), <25% increase in serum creatinine (Scr) (p = 0.0003), and a 50% proteinuria reduction within 15 months of treatment (p = 0.04) were associated with better OS. Multivariate analysis using a proportional hazard model showed that sFLC reduction by >50% (0.006), <25% increase in serum creatinine (Scr) (p = 0.0005) and >50% proteinuria reduction (p = 0.0006) were independently associated with OS. In addition, OS was significantly better among patients achieving >85% reduction in proteinuria than those with < 85% but >50%, p = 0.03 (Figure 1). Patients with >75% reduction in sFLC were more likely to achieve >50% proteinuria reduction (p = 0.009). Most importantly, among those with > 25% increase in Scr, only those patients who had <85% proteinuria reduction had a worse OS (Figure 2a, p = 0.006). There was no difference in OS among those with >85% proteinuria reduction and a rise in Scr of > 25% (Figure 2b, p = 0.77). Conclusion: Renal response is an excellent prognostic marker in patients with AL. This is the first study to show the depth of renal response correlates with OS. Patients who had the highest levels of proteinuria reduction (> 85%) had a significantly better OS than those with >50% but <85%. We also found that the negative impact of >25% decrease in renal function was only pertinent in those who did not have >85% reduction in proteinuria. These findings should help better refine the definition of renal response criteria in AL patients. Disclosures: Leung: Binding Site: Honoraria.

Abstract Abstract 2945 Background: We have previously reported on a Phase II trial using IL-1Ra and dexamethasone, in patients with SMM/IMM, showing that IL-1Ra targets the myeloma proliferative component which parallels a decrease in the C-reactive protein, a surrogate for IL-6 production. (Mayo Clinic Proceedings 84 :114 (Feb. 2009)). In early stage myeloma, IL-6 is a central myeloma growth factor and we have shown that abnormal production of IL-1 β in the myeloma microenvironment stimulates the generation of paracrine IL-6. These patients are the individuals most likely to benefit from anti-cytokine therapy in an attempt to delay/prevent the development of active myeloma. We now present updated results of this study including survival data. Methods: Patients that had ≥ 10% bone marrow plasma cells and/or an IgG or IgA M-spike ≥ 3 g/dL and did not require immediate chemotherapy were eligible. All patients received 100 mg of Anakinra (IL-1Ra) SQ qd for 6 months. Patients with evidence of reduction in M-protein levels continued receiving IL-1Ra alone. Patients with stable disease at 6 months or those with a rising M-protein before 6 months received low dose dexamethasone (20 mg qweek) in addition; the dose was adjusted based on response/toxicity. Results: Data were available on 47 patients based on intent to treat, and pts were classified as smoldering (72%) vs. indolent (28%). All SMM patients were in Group 1 or 2 and thirty-eight patients (81%) had greater than 20% bone marrow plasma cells. All 47 patients received IL-1Ra initially and 25/47 subsequently received IL-1Ra/Dex. Seven patients had a decrease in the plasma cell labeling index (PCLI) on IL-1Ra alone which paralleled a decrease in the high sensitivity C-reactive protein (CRP) in all cases. Three patients achieved a minor response to IL-1Ra alone and 9 patients achieved a PR/MR after addition of dexamethasone. For the group of 47 patients, the median progression-free survival was 45 months and the median overall survival has not been reached. When patients were grouped into whether they exhibited a reduction in the C-reactive protein from baseline after 6 months of therapy, the median PFS for patients without (21 patients) or with (26 patients) a greater than one-third reduction in baseline CRP was 1 year vs more than 8 years (p<.01). Similarly, the median OS for patients without or with a reduction in baseline CRP was 7.9 years vs. median not reached (p=.02; see Figure). Toxicity included injection site reactions during the first month of therapy in 86% of patients. Grade 3–4 adverse events consisted mainly of asymptomatic neutropenia (17% of patients) and infection (18% of patients). Patients that progressed to active MM have been treated with standard therapies including lenalidomide, bortezomib, transplant, and novel therapies. In contrast, seven of the 26 patients with a CRP decrease continue with stable disease and minimal toxicity on IL-1Ra alone or in combination with standard agents. Conclusion: The above results suggest that agents such as IL-1Ra that specifically inhibit paracrine IL-6 production are effective at targeting the proliferative myeloma component and warrant further investigation in combination with standard myeloma therapies. Combination therapy that effectively targets both the proliferative and the IL-1 producing myeloma components may be useful in patients with active myeloma that have an elevated growth rate at diagnosis. Disclosures: Lust: Mayo Clinic: Patents & Royalties. Off Label Use: IL-1Ra use in smoldering myeloma. Donovan:Mayo Clinic: Patents & Royalties.

Abstract Abstract 2950 Background: The median age of patients diagnosed with MM is approximately 70 years, and it is a relatively uncommon disease in the younger population. Both conventional chemotherapy and stem cell transplantation (SCT) have favorably impacted the overall survival (OS) of young MM patients. The median survival of patients < 40 years of age, diagnosed prior to 1993 was reportedly 54 months at our institution. However, the impact of novel agents in this patient population is not well known. We studied the outcome of young patients presenting to our institution over the last decade. Methods: Records of 1538 patients presenting between 01/99 to12/08 were reviewed. The demographics, features and therapeutic interventions in patients up to 45 years of age at diagnosis were analyzed using descriptive statistics. The survival outcome of this group was compared with the remainder of the cohort using the Kaplan-Meier method. Results: One-hundred (6.5%) out of 1538 newly diagnosed MM patients were ≤ 45 years of age at diagnosis. The median follow-up of this group of young patients was 86 months. The disease and patient characteristics are outlined in table 1. A median of 5 regimens (range 1–14) was administered, and 85% patients had received high-dose therapy. 15 patients underwent allogeneic SCT after at least one prior autologous SCT. Novel agents were used both in the front-line and relapsed setting (lenalidomide 60%, thalidomide 56%, pomalidomide 9% and bortezomib 49%), and 45% of initial regimens were novel agent based. The 5 and 7-year OS from diagnosis was 69% and 59%, respectively and the median OS was 93 months. In contrast, the median OS of patients >45 years diagnosed during this period was 53 months (P=0.001, figure 1). Conclusion: A marked improvement in OS of young patients with MM diagnosed in the novel agent era is noted in comparison to the historical control of similar age group. In addition, the age associated survival benefit in the younger patient population prevails in the era of novel therapies. Disclosures: Gertz: Celgene: Honoraria. Lacy:Celgene: Research Funding. Dispenzieri:Binding site: Honoraria; Celgene: Research Funding. Kyle:Millennium: Consultancy; Binding Site: Honoraria. Kumar:Millennium Pharmaceuticals, Inc.: Research Funding; Celgene: Consultancy, Research Funding; Genzyme: Research Funding; Novartis: Research Funding; Merck: Consultancy, Honoraria.

Abstract Background Pomalidomide (POM) is the newest Immunomodulatory agent (IMiDs) that has shown clinical efficacy in relapsed multiple myeloma (MM) refractory to lenalidomide (LEN) and thalidomide (THAL). Studies of MM cell microenvironment suggest that tumor subclones compete for dominance during changes in drug therapy. It was previously observed that a minor clonal population increased in prominence of MM cells after 1 year of treatment with LEN. We examined whether the patients having THAL or LEN as the most recent prior-line therapy affects response to POM. Methods We studied 208 patients enrolled in a phase II trial of POM / dexamethasone between November 2007 and March 2012 at Mayo Clinic, Rochester. We reviewed the immediate prior-line therapy before enrollment in our trial. Comparison of treatment duration of POM and response rates were conducted between patients who had either THAL or LEN as latest prior-line therapy, and patients who were treated with non-IMiDs immediate before enrollment in POM trial. Treatment duration of POM was estimated using Kaplan Meier method and the survival curves were compared using log-rank test. We used univariate Cox proportional hazard models to estimate the prognostic impact of different variables. Results The median age of patients was 63 (range from 32 to 88). 68 % were males. 80 patients (38.5%) had THAL or LEN immediate prior to POM. Median prior-line therapies were 3. Patients who received THAL or LEN immediately prior to POM had a lower response rate than those who had non-IMiDs as latest therapy (29% vs 44%, p 0.04) and shorter median duration of POM treatment (5.7 months vs 7.3 months, p 0.02). In 190 (91%) patients who were previously treated with LEN and THAL at any time, median time between the end of LEN or THAL treatment and the initiation of POM was higher for POM responders than non-responders (10 months vs 3 months, p 0.0008). Patients responded to POM had a shorter duration of prior LEN or THAL treatment compared to non-responders (9 months vs 15 months, p 0.001). Conclusion THAL or LEN as an immediate prior-line therapy to POM is associated with a lower response rate and shorter effective treatment duration. Longer interval between prior immunomodulatory compounds and POM, and shorter exposure to previous immunomodulatory compounds are associated with better POM treatment response. Disclosures: Gertz: Celgene: Honoraria. Kumar:Merck: Consultancy, Honoraria; Celgene: Consultancy, Research Funding; Millennium: The Takeda Oncology Company: Research Funding; Novartis: Research Funding; Genzyme: Research Funding. Lacy:Celgene Corporation: Research Funding.

Abstract Background Multiple myeloma (MM) is uncommon in patients below 40 years of age. Between 1960 and 1992 when stem cell transplantation (SCT) was rarely performed and novel agents were unavailable, overall survival (OS) was reported to be 54 months in the Mayo Clinic series of patients with MM below forty years of age. The impact of novel agents or SCT in this population is unclear. Herein, we report the outcomes of patients under 40 years of age who were evaluated over a span of more than five decades with a focus on the periods contemporaneous with the introduction of SCT and novel agents, the major therapeutic milestones in the management of MM. Methods We analyzed the medical records of patients with MM under 40 years of age who were evaluated at Mayo Clinic, Rochester, MN between 1/1/1960 and 12/31/2011. SCT and novel agents were utilized infrequently prior to the years 1990 and 2000, respectively. Patients were therefore divided into three cohorts by the year of diagnosis of MM: Group A (1960 -1979), Group B (1980 to 1999) and Group C (2000 –2011) to assess the impact of major therapeutic advances (i.e. Increased utilization of SCT and novel agents compared to conventional chemotherapy). OS was calculated by the Kaplan -Meier method. Results Out of 8063 unique MM patients seen at our institution during this period, 174 (2%) patients were under 40 years of age at diagnosis. The median age at diagnosis was 36 years (range: 19-39). The estimated median follow-up of the entire cohort was 179 months (95% CI: 149-196 months). The median OS of the entire cohort was 76 months (95% CI: 45-80 months) from diagnosis. The median OS of patients in Groups A (n=29, 17%), B (n=93, 53%), and C (n=52, 30% ) was 44 months (95% CI: 20- 76), 79 months (95% CI: 46-97), and 92 months (95% CI: 42-NR), respectively (p=0.005). No significant OS difference was noted between Groups B and C (Figure). Sixty-six (38%) patients underwent at least one SCT (autologous: 56 patients and allogeneic 10 patients). The utilization of SCT increased over the three time periods from Group A 0%, Group B 39% and Group C 58% (p<0.001). Of 153 patients in whom front-line therapy-related data were available 118 (77%) received conventional and 35(23%) received novel agents. The median OS of patients who underwent transplantation (n=66) was 93 months compared to 46 months for those who did not (n=108, p=.01). In the 66 patients who underwent SCT, the median OS was 93 months for conventional agents-based induction (95% CI: 73-143) versus 97 months (95% CI: 41-187) for novel agent based induction (p=.4). Sixty-eight (40%) patients received novel agents at some point during the course of their disease [bortezomib 35 (54%), thalidomide 44 (67%), lenalidomide 47 (71%) and pomalidomide 7(11%)]. The median survival of these patients was 131 (95% CI: 88-161) months versus to 46 (CI: 37-74) months for those (n=106) receiving conventional agents only (p=0.0002). Conclusions OS of patients with MM under 40 years of age in the pre-transplant era (Group A) was significantly shorter than that of patients diagnosed in the era of SCT (Group B) and SCT plus novel agents (Group C). Although improvement of survival outcomes is evident with utilization of novel agents, similar outcomes of Groups B and C indicate lack of incremental benefit over SCT with utilization of novel agents. Maximal survival gain coincides with the introduction of SCT in this unique patient cohort. Disclosures: Kumar: Celgene: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Onyx: Consultancy, Research Funding.

Abstract Abstract 2942 Background: Pomalidomide (pom) is a distinct immunomodulatory (IMid) drug with high response rates in relapsed MM, including patients previously treated with thalidomide, bortezomib and lenalidomide. However, its duration of response and long term outcome is unknown. We evaluated the long term outcomes of the first Mayo Clinic cohort of pts treated with Pom. Methods: Pts with relapsed/refractory myeloma with 1–3 prior therapies were enrolled. Pom 2 mg/d was given orally continuously on 28 day cycle with weekly dexamethasone 40 mg. All pts received DVT prophylaxis with aspirin, heparin or warfarin. Results: 60 pts with relapsed MM were enrolled from Nov 2007-Aug 2008. Median age was 65.5; 36 were male. Median time from diagnosis was 45.6 mo (9.–-192.5). Nineteen (32%) were high-risk according to mSMART (msmart.org), and 78% were ISS Stage 2/3. Prior therapies included transplant (65%), bortezomib (33%), thalidomide (47%), lenalidomide (35%) [previous IMiD 60%] and radiation (38%). Toxicities at least possibly attributed to Pom included G3/4 anemia (5/0%), leukopenia (17/3%) and thrombocytopenia (3/0%). G3/4/5 non-hematological toxicities occurred in 30 (50%) and included fatigue (18/0/0%), pneumonia (8/2/2%), hyperglycemia (5/0/0%) and constipation (5/0/0%). Only one pt had grade 3 neuropathy. Treatment adjustment for occurred in 30 pts (50%) for pom (mostly for neutropenia) and 35 pts (58%) for dex. A median of 11.5 cycles were administered. With median follow up of 30.1 months (mo), overall response was seen in 39 (65%) [4 sCR, 5 CR, 16 VGPR, 14 PR]. Median time to first reponse (≥PR) was 1.7 mo (0.8–14.8). Median duration of response (in responders of ≥PR) was 21.3 mo. Median PFS was 13 mo and the 2 year OS rate was 76%. Standard risk pts had median PFS of 18.4 mo and 2 year OS rate was 85%; high risk pts had median PFS of 9.2 mo and 2 year OS rate was 57%. (Figure 1) Conclusions: Pom/dex is highly effective and well tolerated in relapsed MM, with a response rate of 65% even in pts with multiple prior therapies, including other IMiDs, bortezomib and transplant. The response is also durable, with median duration in excess of 21 months. Pom/dex provides long term benefit with median PFS 13 months and 2 year OS rate of 76%. Disclosures: Kumar: Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees. Stewart:Celgene Corporation: Consultancy, Research Funding; Millenium: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Onyx: Consultancy, Research Funding. Fonseca:Consulting :Genzyme, Medtronic, BMS, Amgen, Otsuka, Celgene, Intellikine, Lilly Research Support: Cylene, Onyz, Celgene: Consultancy, Research Funding. Lacy:Celgene: Research Funding.