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Introduction With the introduction of novel agents, survival in multiple myeloma has successively increased in the past decade. This improved survival increases the risk for late complications. Patients continue to receive melphalan therapy as a standard induction for those over the age of 65. Lenalidomide is considered a standard component of induction therapy in the United States for patients who are transplant candidates. Stem cell transplantation remains the standard of care for patients eligible to receive it. As a consequence of exposure to lenalidomide, stem cell transplant, and melphalan, the risk of late myelodysplasia and acute leukemia remains significant. We reviewed the Mayo Clinic experience with therapy-induced myelodysplasia beginning with the advent of novel agents. Patients and Methods All patients that carry the diagnosis of multiple myeloma between January 1, 2000, and September 1, 2011, were included. Patients with a synchronous diagnosis of a myeloproliferative or a myelodysplastic disorder or those who developed the myelodysplastic disorder within 15 months of first chemotherapy exposure were excluded. The date of diagnosis for the purpose of this abstract was based on first exposure to chemotherapy and not first detection of a monoclonal protein or smoldering multiple myeloma. All patients had to have morphologic verification in the bone marrow of dysplastic change consistent with therapy-related myelodysplasia. Results Of 3111 patients who had a myeloma diagnosis and first treatment after January 1, 2000, through September 1, 2011, 22 patients were identified to fulfill the criteria of myelodysplasia. There were 13 men and 9 women with a median age of 67 (46 to 82). At the time of this report, 17 have died. Prior to the development of myelodysplasia, exposure to an alkylating agent, lenalidomide, or an auto stem cell transplant was seen in 13, 15, and 10, respectively. Only one patient had been exposed to lenalidomide alone. Eighteen patients were classified as myelodysplasia. Four had acute non-lymphocytic leukemia. Metaphase cytogenetics was available in 19 and only one was normal. Twelve were hypodiploid. Trisomy 8 or abnormalities of chromosome 5 and 7 were present in 13. Seven patients received a hypomethylating agent with no clear evidence of response in any. Four patients had an allotransplant to manage the MDS/AML and only one survives 487 days after a matched-related donor allogeneic transplant. The median time from initial therapy of multiple myeloma to recognition of MDS or AML was 50.9 months (range: 15.2-146.5 months) fig 1. The median overall survival of the 22 patients is 6.5 months. Fig 2 Six of the 22 had active myeloma at the diagnosis of MDS/AML. Conclusion Myelodysplasia during the era of novel agents is a devastating complication of therapy with a very short survival and low response rate. As a time-dependent complication, the overall risk cannot be accurately estimated but has occurred in <1% of our patient population to date. Hypomethylating agents were ineffective in the seven that received it. One of four allotransplant patients remains alive. Ongoing surveillance for MDS/AML in this population is warranted and more effective therapies are needed. Disclosures: Kumar: Onyx: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.

Background: Therapy-related MDS/AML (t-MDS/AML) is a common and devastating complication of treatment with alkylating agents and topoisomerase II inhibitors, often employed with curative intent, in standard or high-doses, in the treatment of hematological malignancies and solid tumors. Allogeneic HSC transplant is considered the standard treatment for t-MDS/AML but its applicability is limited by the unavailability of donors, comorbidities in the recipient and risk of acute and chronic graft-versus-host disease. Patients carrying diseases commonly treated with high-dose chemotherapy and autologous HSC transplant (such as multiple myeloma and non-Hodgkin lymphoma) who latter develop t-MDS/AML occasionally have stored HSC harvested prior to the diagnosis of the secondary malignancy (hereafter called early-stored HSC). The benefit of using early-stored HSC to support myeloablative therapy for the treatment t-MDS/AML is unknown. Methods: Retrospective, single center analysis of patients with t-MDS/AML receiving myeloablative chemotherapy with or without irradiation supported with early-stored HSC. Results: Six patients received early-stored HSC transplant for treatment of t-MDS/AML between 2000 and 2007. Median age at the time of the transplant was 57 years (range 15–71). Three patients had been primarily diagnosed with follicular lymphoma, 2 with multiple myeloma and 1 with Ewing’s sarcoma. One patient had received prior autologous HSC transplantation. Two patients developed AML, 1 patient CMML, 1 patient RCMD, 1 patient RAEB1 and 1 patient RAEB2. Median time from diagnosis of primary malignancy to HSC harvesting was 26 (2–122) months and from harvesting to development of t-MDS/AML 44 (7–79) months. Conditioning regimen was Cy/TBI in three patients, BuCy in 2 patients and Samarium + Melphalan in one patient. Five patients engrafted neutrophils and 4 patients engrafted platelets 10–34 and 13–126 days after transplant respectively. In 3/6 patients there was disappearance of the pre-transplant chromosomic abnormality (2 patients -7 and 1 patient -7 and t(1;7)). Two patients obtained hematologic CR and two patients obtained CR without full recovery of platelets. One patient died of sepsis 230 days after transplant, one died with refractory disease on day 103 after transplant and one patient is alive with recurrence of t-MDS. Three patients are alive and free of disease 7, 73 and 87 months after transplant. Conclusion: Myeloablative conditioning followed by autologous, early-stored HSC transplant can provide prolonged survival to patients with tMDS/AML not suitable to allogeneic SCT.

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.