Hayman, Suzanne R.

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 3101 The POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome is a rare paraneoplastic disorder secondary to a clonal plasma cell process. The most experience with successful outcomes in POEMS with disseminated disease has been with high dose chemotherapy followed by autologous stem cell transplantation (ASCT). However, the risk of relapse of POEMS following an ASCT or the outcome of the patients who relapse is not known. We therefore performed a retrospective review of POEMS patients who underwent ASCT at our center and subsequently relapsed or progressed. Over the past 12 years, 58 patients with POEMS underwent autologous stem cell transplantation at the Mayo Clinic, Rochester between Mar 18, 1999 and Jun 22, 2011. With a median follow up of 40 months (1–147 months), 12 patients have relapsed. The median time to relapse was 41 months. The 1, 2, and 5 year PFS rates were 98%, 94%, and 75%, respectively (Figure 1), and the 1, 2, and 5 year OS rates were 98%, 98%, and 94%. Of the 12 patients with documented relapse, 7 had baseline PET/CT scans all of which had FDG avid lesions. By 1 year, the FDG avidity had not resolved in 4 of these patients who then went on to either develop additional lesions or increasing SUV of existing lesions. Of the 12 patients with documented relapse, 8 had baseline VEGF measurements, and all but 1 had normalization by 1 year. The first sign of relapse was a clinical deterioration in 2, a rising M-protein in 3, and a rising plasma VEGF level in 5 patients. All of these patients had new or worsening of existing lesions on PET/CT scan (n= 9) or x-ray imaging (n= 3). The symptoms of clinical relapse included pain at the site of the lytic lesion and generalized pain with swelling. Of the patients who relapsed, 5 were treated with radiation therapy, 4 received lenalidomide or thalidomide, 2 had alkylator based therapy and 1 had bortezomib based therapy. One patient was treated with surgical resection of his hepatic plasmacytoma and 2 patients have been observed without needing definitive treatment as of yet. One patient also received anti-VEGF treatment with bevacizumab unsuccessfully after failing cyclophosphamide therapy. In this large cohort of POEMS patients treated with high dose chemotherapy and autologous stem cell transplantation in a single center, a relapse rate of 21% was noted. Not every patient who relapsed has been deemed to need further treatment, and most patients could be salvaged with chemotherapy or radiation. Only one patient died from relapsed POEMS following stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 3095 Background: Although HDM is the standard conditioning for pts with MM undergoing ASCT, it is not sufficient for cure. In an effort to improve upon this standard, we added escalating doses of Y-90 Zevalin (a murine IgG1 kappa monoclonal antibody Ibritumomab conjugated to Y-90) to HDM in a standard 3+3 phase I trial design. Y-90 is a beta-emitting radioisotope with a path length of 5 mm allowing it to target CD20+ cells and bystander cells within 5 mm. Methods: Eligibility included being a candidate for ASCT. Consenting patients (pts) received: day -22, rituximab 250 mg/m2 with In2B8 for scanning; day -14, rituximab 250 mg/m2 with escalating doses of Y90-Zevalin; day -2 and -1, melphalan 100 mg/m2/day; day 0, at least 2 × 10(6) CD34/kg stem cells; and GM-CSF until ANC engraftment. The 6 dose levels (DL) were (in Gy): 10; 12; 14; 16; 18; and 20. Dose limiting toxicity (DLT) was defined as: sustained pulmonary or liver toxicity (grade3; 96 hours duration or VOD that does not resove by day 30); delayed engraftment (ANC < 500 at day 21 or platelet transfusion dependence at day 35); and non-hematologic grade (gr) 4 toxicity excluding gastrointestinal or constitutional. Responses were according to IMWG criteria. Accrual was between May 2005 and June 2011. Data was frozen as of August 2, 2011. Results: Thirty pts have been accrued: DL1, 3; DL2, 3; DL3, 3; DL4, 6, DL5, 6; DL6, 6. The median age of patients was 59 (range 32, 73), and 70% were male. 60% had ASCT as primary therapy. The other patients were transplanted in chemosensitive relapse (n=3), chemoresistant relapse (n=7), and untested relapse (n=2). Median time from diagnosis to protocol therapy was 10.4 months (range 3.5, 94.3). Five pts had prior radiation therapy, and 11 had prior ASCT. Maximum tolerated dose (MTD) of Zevalin with fixed dose melphalan 200 mg/m2 was DL 5 (18 Gy) which amounted to 168 mCi (124, 182) administered. No DLTs were observed at DL 1, 2, 3, or 5. There was 1 DLT at DL 4, comprising hepatic failure (gr 5) CMV viremia (gr 3), and delayed engraftment, in a 73 yo patient with chemoresistant relapsed disease, and 2 DLTs at DL 6. These DL 6 DLTs included: 1) fatal bowel necrosis (day 12 post ASCT) in a 67 yo patient with relapsed refractory MM and history of CAD, ischemic colitis, DM; and 2) fatal biopsy proven venoocclusive disease (gr 5), which began day 91 post ASCT in a 62 yo patient with primary refractory MM, peri-mobilization S. aureus bacteremia with septic embolic, and line associated venous thrombosis. Overall, gr 3 or higher AEs were observed in 100% of pts. Non-heme gr 4 AEs were seen in: DL1, 1; DL2, 2; DL3, 0; DL4, 1; DL5, 0; DL6, 4. Median time to ANC >=500 and plts>=50 was 11 (range 8, 17) and 15 days (range 11, 89). Confirmed response rates from immediately pre-protocol to best confirmed response were: CR, 5; VGPR, 5; continued VGPR, 4, and continued PR, 7. If one includes best confirmed response from baseline for those patients using transplant as primary consolidation, 4 PRs are upstaged to VGPRs. Median follow-up for all pts is 24.5 months (0.8, 64.8), and 10 pts have died. The median PFS for pts proceeding to early and delayed ASCT was 30.4 months (95%CI 4.1-NR) and 10.3 months (95%CI 2.8–21.7), respectively. The median OS for pts proceeding to early and delayed ASCT was not attained and 11.4 months (95%CI 2.8-NA), respectively. Conclusions: For patients with multiple myeloma, the MTD of Zevalin with fixed high-dose melphalan is 18 Gy. The combination of a VGPR plus continued VGPR rate of 60%, a median PFS of 13.1 months, and a 73% 1 year OS rate make this a regimen worthy of further study. Disclosures: Kumar: Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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 Abstract 2992 Background: Patients with myeloma receiving initial therapy with lenalidomide-based regimens can have difficulty collecting adequate stem cells for an autologous transplant. Stem cell collection in these patients can be significantly enhanced by addition of the CXCR-4 antagonist plerixafor to the mobilization regimen. Plerixafor is typically given subcutaneously (SQ), with collection approximately 11 hours after injection to obtain maximum yield. Intravenous administration can potentially allow more rapid and predictable mobilization compared to the SQ route. We designed this trial to prospectively assess the efficacy of intravenous plerixafor administration in patients undergoing lenalidomide therapy. Patients and methods: Patients who were receiving initial therapy with a lenalidomide-based regimen and were undergoing stem cell collection within 12 months of their myeloma diagnosis were enrolled. Patients received GCSF at 10 μg/kg/day for 4 days followed by addition of plerixafor at 0.24 mg/kg/dose starting on day 5. Plerixafor was administered intravenously early morning (6–7 am) followed by apheresis beginning 4–5 hours later. Plerixafor was administered for a maximum of 4 days; but patients could continue apheresis beyond the 4th day at treating physician discretion. The aims of the study were to determine the proportion of patients reaching a stem cell yield of at least 3 million CD34 cells/kg by second day of apheresis, the safety and tolerability of intravenously administered plerixafor, and the overall rate of failure to mobilize (defined as less than 2.5 million CD34 cells/kg in 4 collections). Results: Thirty-seven patients were accrued between December 2009 – April 2011, and 36 were eligible for analysis. The median age was 61 years (range; 28–73); 61% were male. The median time from start of initial therapy to enrollment was 4.6 months (range; 2.6 to 11.1) and the median cycles of lenalidomide were 4 (range; 3–11). Thirty-four (94%) of the patients achieved at least 3 million CD34 cells/kg within 2 days of apheresis. The median CD34 cells/kg after 1 day of collection was 3.9 million (range; 0.7 to 9.2) and after two days of collection was 7.02 million (range: 1.1–16.5). Two patients failed the mobilization (<2.5 million CD34 cells/kg). There were no grade 3 or 4 non-hematological adverse events and one patient experienced grade 4 thrombocytopenia. The most common grade 1 or 2 adverse events seen were gastrointestinal, namely nausea, diarrhea and abdominal pain or bloating. Grade 1 dizziness was reported in 8 patients. Overall, the infusion was well tolerated. Conclusion: Intravenously administered plerixafor is an effective strategy for mobilization in this patient group with low rate of failure to mobilize. It is well tolerated with toxicity comparable to the SQ administration. It also offers flexibility in patient scheduling with a convenient schedule for early morning infusion followed by apheresis later in the day. Disclosures: Kumar: Merck: Consultancy, Honoraria; Celgene: Consultancy, Research Funding; Millennium Pharmaceuticals, Inc.: Research Funding; Genzyme: Research Funding; Novartis: Research Funding. Off Label Use: Use of the investigational agent MLN9708 for the treatment of previously untreated multiple myeloma. Lacy:Celgene: Research Funding.

Abstract Background Acquired factor X (FX) deficiency is associated with immunoglobulin light chain (AL) amyloidosis and may be accompanied by hemorrhage. There are limited data on the effects of autologous stem cell transplant (ASCT) on FX deficiency. We reviewed hemorrhagic complications and the effect of high dose melphalan (HDM) and ASCT on FX levels in AL amyloidosis patients with FX deficiency. Methods We conducted a retrospective chart review of patients with AL amyloid with FX levels below 60%, not on chronic anti-coagulation who underwent HDM/ASCT at the Mayo Clinic, Rochester, MN between 1995 and 2011. Results Forty-one of 358 patients (11%) met our study criteria. Median pre-ASCT FX was 45% (range: 2%, 59%). The most common bleeding complication was central line associated n=15 (37%) followed by gastrointestinal n=10 (24%) and genitourinary n=9 (22%). The most frequent and severe bleeding complications occurred in patients with FX levels less than 10%. Four patients required emergent splenectomy owing to splenic rupture; one of these patients died from hemorrhagic shock. Periprocedural prophylaxis included activated recombinant Factor VII (rFVIIa) infusions, fresh frozen plasma (FFP) infusions and platelet transfusions. rFVIIa was efficacious in controlling bleeding during splenectomy (n=5) and, in conjunction with arterial embolization, for retroperitoneal bleed (n=1). Elective splenectomy for FX deficiency (n=1) resulted in only transient improvement in FX level. No relationship between the degree of pre-ASCT FX deficiency and other laboratory values (alkaline phosphatase, AST, total bilirubin, serum albumin, total serum protein, serum creatinine, total urine protein, beta2 microglobulin, troponin T) was found. Post-ASCT FX levels were determined in seventeen patients. In four of these patients, post-ASCT FX levels were determined in the acute/subacute phase of ASCT before steady state FX levels could be achieved; the median change in FX for these patients was -6.5% (range: -19%, 3%). In the remaining thirteen patients, who were between 99 and 1920 days from ASCT, FX improved by median 26% (range: -15%, 92%). Overall post-ASCT FX increased in twelve of thirteen (92%) patients. The improvement in FX correlated with improvement in the degree of proteinuria (p = 0.04) and showed a trend towards significant correlation with improvement in serum alkaline phosphatase (p = 0.06). Conclusions Hemorrhagic complications are most frequent and severe for FX levels below 10%. rFVIIa infusions, FFP and platelets were effective prophylactic agents. In the single patient who underwent elective splenectomy, a transient improvement in FX level was seen. Splenectomy was otherwise reserved for patients with splenic rupture/hematoma. Post-ASCT FX levels increased in twelve (92.3%) of the remaining thirteen patients; five of the patients (38.5%) were no longer FX deficient after ASCT. The degree of improvement in FX levels was correlated with improvement in markers of renal or hepatic involvement by amyloid. Disclosures: Kumar: Celgene: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Onyx: Consultancy, Research Funding.

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.

Abstract Abstract 4120 Introduction: Autologous stem cell transplantation (ASCT) remains an effective treatment for immunoglobulin light chain (AL) amyloidosis but its high treatment related mortality is a concern. The development of acute renal failure can strongly affect the survival of these patients. This study looks at the impact of the timing of dialysis initiation on the overall survival (OS). Methods: AL patients who underwent ASCT from 3/96 to 1/10 were selected. Patients were placed into 4 groups: I - never dialyzed, II - initiated dialysis prior to ASCT, III - dialysis began within 30 days of ASCT and IV - dialysis was started after 30 days of ASCT. Results: Four hundred and ten patients were selected for study and 75 (18.3%) received dialysis. Baseline characteristics are listed in Table 1. In univariate analysis, serum creatinine (Scr) and b-2 microglobulin (b2m) were associated with dialysis post-ASCT. Both became non-significant in the multivariate model suggesting they are co-dependent. Dialysis had a strong influence on survival, p < 0.001 (Fig 1). This was most evident when dialysis was started after ASCT (group III (p = 0.003) and IV (p = 0.004)), but not before (II, p = 0.19).To explore the interactions of dialysis with cardiac biomarkers in their relationship with OS, cardiac troponins T (cTnT) and N terminal-pro-brain natriuretic peptide (NT-pro-BNP) were analyzed with timing of dialysis in a proportional hazard model. Timing of dialysis (p < 0.001), cTnT (p = 0.03) and NT-pro-BNP (p = 0.03) all were associated with OS. Using Receiver Operator Characteristic (ROC) curves, best cut points were chosen for cTnT (0.01 ng/ml) and NT-pro-BNP (1350 pg/ml) for survival. When treated as categorical variables, the proportional hazard model found that only NT-pro-BNP (p = 0.002) and timing of dialysis (p < 0.001) were independent predictors of OS but cTnT had loss its significance (p = 0.07). Using Kaplan Meier method, dialysis was a significant risk factor in patients with low cTnT and both high and low NT-pro-BNP (p < 0.001) but not in patients with elevated cTnT (p = 0.25). Discussion: The timing of acute renal failure strongly affects the OS of AL patients undergoing ASCT. In our study, patients who started dialysis prior to ASCT did not have an inferior OS compared to patients who never needed dialysis. On the other hand, starting dialysis after ASCT significantly shortened OS. The timing of dialysis was an independent predictor of OS even when combined with cardiac biomarkers. NT-pro-BNP appears to be the stronger marker when timing of dialysis is considered in the multivariate analysis. Disclosures: No relevant conflicts of interest to declare.