Hayman, Suzanne R.

Abstract Abstract 3469 Introduction: Stem cell transplantation is important in the management of multiple myeloma. In the United States, the standard of care is administration of growth factors to accelerate neutrophil recovery after stem cell transplant. The need for growth factors after transplant has not been investigated recently. Patients: We analyzed a cohort of 166 patients at our institution who underwent autologous transplant for multiple myeloma without receiving growth factors after transplant and compared them with 498 patients who received standard filgrastim beginning on posttransplant day 5. TABLE Results: A neutrophil count of 500/μL was achieved in a median of 12.5 days in patients receiving growth factor, compared with 13.5 days in those not receiving growth factor (P<.001) Fig 1. Platelet engraftment was identical (median, 14.5 days; P=.12) in both groups, despite a lower median number of CD34+ cells infused in patients who did not receive growth factors. Incidence of nonstaphylococcal bacteremia was identical in both groups. The median hospital stay was 3.5 days shorter in the group not receiving growth factor. Bacteremia impacted platelet but not neutrophil engraftment. Figure 2 Conclusion: It is feasible and reasonable to perform autologous stem cell transplant for multiple myeloma without administering growth factors. Estimated savings would be $4,600 for each transplanted patient. Growth factor administration is not required for a safe outcome and decreases the number and severity of some of the fluid-related complications after transplant such as acute respiratory distress syndrome, allergic reactions, alveolar hemorrhage, and rarely splenic rupture. Disclosures: Gertz: Celgene: Honoraria; Millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lacy:Celgene: Research Funding. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

Abstract Abstract 4518 Introduction: Autologous stem cell transplant (PBSCT) is an integral part of the management of Multiple Myeloma (MM). Available data suggest that the timing of PBSCT has no effect on overall outcome. Some patients currently opt to delay their transplant, especially in this era of proteosome inhibitors and iMIDs. In such patients the best time for stem cell collection is unknown. We conducted a retrospective study looking at early stem collection and storage compared to stem cell collection at the time of transplant in patients who opt to be transplanted at a later date. Method: All patients who had PBSCT performed more than one year from the time of diagnosis were reviewed. Two groups of interest were then evaluated. Early collection (ET): those who had stem cells collected within 6 months of diagnosis, and Late collection (LT): those who had stem cells collected more than 1 year from diagnosis and within 3 months of PBSCT. Results: Table 1 shows some patient characteristics. 334 patients were identified, ET (85) and LT (249). Gender distribution, Durie Salmon stage, immunoglobulin subtype and cytogenetic abnormalities were similar in both groups. The LT group was older 60 yrs compared to ET 56.6 yrs, P=0.02. More patients in the ET (77%) group were mobilized with cyclophosphamide compared to LT (51%) p<0.0001. Stem cell yield was similar in both groups 9.26 × 10(6) CD34/kg in ET and 8.19 × 10(6) in LT, P=0.16. Median number of collections was 3 in both. More patients in the LT (67%) received Melphalan 200 mg/m2 conditioning compared to ET (59%) p=0.03. Neutrophil engraftment occurred at day + 11 ET and +12 (LT) p<0.0001. ET patients achieved platelet engraftment on day + 13 compared to + 15 (LT) p=0.002. Complete response rates were similar 30% (ET) and 34% (LT). Duration of response after PBSCT was not different 12.6 months (ET) and 11.6 months (LT). Median overall survival from diagnosis was 70.5 months (ET) and 74.5 months (LT) p=0.5. Similarly there was no difference in overall survival post PBSCT 33.5 month (ET) and 32.2 months (LT). Conclusion: Stem cell collection and storage early in the disease course of multiple myeloma results in early engraftment compared to stem cell collection at the time of transplant in patients who opt for a delayed transplant. More studies looking at cost analysis will however be need to determine the cost effectiveness of early versus late stem cell collection. Disclosures: Dispenzieri: Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding. Gertz:Celgene: Honoraria; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract Background: Ixazomib is an experimental, orally bioavailable, proteasome inhibitor that has demonstrated anti-tumor activity in relapsed multiple myeloma (MM). In the dose escalation studies, ixazomib was tolerated up to a dose of 5.5 mg given every week as a single agent, while a dose of 4 mg was utilized in the combination studies with lenalidomide. We undertook this study to examine the efficacy and tolerability of the two doses of ixazomib in combination with dexamethasone in patients with relapsed MM. Patients and methods: This was a randomized phase 2 study of two doses of ixazomib (4mg; Arm A or 5.5 mg; Arm B) given weekly for three weeks with a week off along with weekly dexamethasone (40 mg) in patients with relapsed MM, who are proteasome inhibitor na•ve (including bortezomib) or have received less than 6 cycles of therapy with bortezomib and had a PR or better with no progression at the time of discontinuation. The primary objective was to determine the confirmed overall response rate (>=PR); secondary objectives included progression free and overall survival. A total of 71 patients were accrued from February 2013 to April 2015; one patient was ineligible. Results: Baseline characteristics were similar in the two arms; median age across the study was 70 years (46-84); 53% were male. Median number of prior therapies was 4 (range 2-6); 90% of the patients had prior IMiDs, 70% had prior transplant and 29% had prior bortezomib. At a median follow up of 10 months, 17 (49%) and 19 (54%) of patients had disease progression in arms A and B respectively with 12 (34%) patients in each arm still continuing on treatment. All patients in each arm were evaluable for response; the overall response rates were 31% in arm A (95%CI: 17-49) and 51% (95%CI: 34-69) in Arm B. The depth of response, event free survival and overall survival are outlined in Table 1. Among the patients with no prior bortezomib exposure the response rates were 38% for Arm A and 52% for Arm B. The treatment was well tolerated with 2 patients in each arm discontinuing treatment for adverse events; there were no on study deaths. A grade 3 or higher AE that was at least possibly related to treatment was seen in 21% and 54% in Arms A and B respectively; with 15% and 37% hematologic and 6% and 29% non-hematologic AEs. The most common attributable toxicities encountered included fatigue, thrombocytopenia, diarrhea and nausea with more grade 3 toxicities among Arm B. Peripheral neuropathy, possibly related to ixazomib, was seen in 55% (only grade 1 or 2) in arm A and 43% (2 patients with grade 3) in Arm B. Toxicities led to dose reduction of ixazomib in 17% and 43% of patients in Arm A and B respectively; the median number of cycles administered were 5 (1-24) and 5 (1-22) respectively. Conclusions: Ixazomib in combination with dexamethasone was well tolerated with significant anti-myeloma activity in this group of patients with relapsed MM. Deep responses including stringent CR were observed. The higher dose of ixazomib appears to be associated with a higher response rate but with higher rate of adverse events requiring dose reductions. Table 1. Treatment outcome in all patients Arm B (4 mg) (N=35) Arm C (5.5 mg) (N=35) Response Rate 31% (95%CI: 17-49) 51% (95%CI: 34-69) No. of Responders 11 18 sCR 0 1 CR 1 0 VGPR 7 8 PR 3 9 MR 5 1 Median Overall Survival1 NA NA 6 Months 100% 100% Median Event Free Survival1,2 8.4 mos (95%CI: 4.3-13.2) 8.2 mos (95%CI: 3.8-16.3) %Event Free at 6 Months 60% (95%CI: 45-81) 60% (95%CI: 45-81) Median Duration of Response1 16.7 mos (95%CI: 9.3-22.0) 16.3 mos (95%CI: 7.0-20.1) Median Time to Response 1.1 mos (range: 0.8-3.6) 1.0 mos (range: 0.8-7.5) CI: confidence interval; mo: month; NA: not attained 1Kaplan Meier 2Event-free survival time is defined as the time from registration to the first of disease progression, death due to any cause, or subsequent treatment for multiple myeloma. Disclosures Kumar: Celgene: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Skyline: Consultancy, Honoraria; Onyx: Consultancy, Research Funding; Novartis: Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; BMS: Consultancy.

Abstract Abstract 3468 Engraftment syndrome (ES) is a complication of hematopoietic stem cell transplantation classically characterized by fever, rash, diarrhea, weight gain and non-cardiogenic pulmonary edema. Renal failure has been observed but is not considered to be a major part of the syndrome. We have noted that acute renal failure (ARF) is common around the time of leukocyte engraftment in light chain amyloidosis (AL) patients after autologous stem cell transplant (ASCT). We suspect this is due to ES and this retrospective review was conducted to further study this entity. Data were collected from 377 AL patients who underwent ASCT from 7/1997 to 10/2009. Patients who experienced an elevation of serum creatinine (Scr) > 0.5 mg/dl within 4 days of leukocyte engraftment were selected. Patients who carried a diagnosis of ES were also included regardless of Scr elevation. Nephrotoxic insults were reviewed. Vitals were collected. Forty-one patients met criteria. Four patients were found not to have ES, 2 sepsis, 1 allergic interstitial nephritis (AIN), 1 acute cellular rejection. ES was noted in 37 (9.8%) patients, 2 presented with mainly pulmonary ES and 8 had both pulmonary and renal involvement. The degree of renal failure varied from mild and self-limited to severe and requiring dialysis. The renal failure is usually preceded by fever, rash, increasing edema, relative hypotension and low urine sodium (Figure 1). Treatment with glucocorticoids (60 mg/d) was successful in reversing the renal failure in most patients but those with pulmonary involvement required higher doses. Our study showed that ES presents more commonly with renal failure than pulmonary involvement in AL patients. Further complications may be prevented by early treatment with corticosteroids once infection is ruled out. Dosing depends on concurrent pulmonary findings. Distinguishing ES with AIN is difficult as presentations are similar but AIN will continue until the offending drug is removed while ES generally responds quickly to steroids alone. Figure 1. Figure 1. Disclosures: Dispenzieri: Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

Abstract Background: Cytogenetic evaluation, especially using fluorescence in situ hybridization (FISH), at the time of diagnosis is essential for initial risk stratification and the employment of risk-adapted treatment strategies in multiple myeloma. Little is known about the occurrence and prognostic significance of cytogenetic evolution during follow up. Methods: We studied 433 patients who were diagnosed with multiple myeloma between January 2000 and December 2011 and had at least two FISH evaluations at Mayo Clinic Rochester, including the diagnostic specimen. Bone marrow aspirates were evaluated for deletions, monosomies, trisomies, and tetrasomies using chromosome- or centromere-specific FISH probes. IGH rearrangements were evaluated using an IGH break-apart probe and up to five potential partners (FGFR3, CCND1, CCND3, MAF, and MAFB). Cytogenetic evolution was defined as a new deletion, monosomy, trisomy, tetrasomy, or translocation during follow up. Multivariable-adjusted logistic regression models were used to assess the associations between the parameters of interest and the presence of cytogenetic evolution in follow-up specimens. Multivariable-adjusted Cox proportional hazards models were used to assess the effect of cytogenetic evolution on overall survival. All models were adjusted for sex, age, the presence of high-risk FISH abnormalities, and the number of abnormalities at the time of diagnosis. Likelihood ratio tests were used to assess the goodness of fit of nested models. The χ2 or Fisher's exact test was used to assess the distribution of cytogenetic abnormalities in subgroups. Results: The median age at diagnosis was 60 years (32 - 82), 264 (61%) of the patients were male. The median overall survival for the entire cohort was 7.0 years (6.2 - 7.8). At the time of diagnosis, 150 (35%) and 57 (13%) of the 433 patients presented with a hyperdiploid karyotype and cytogenetic high-risk abnormalities, respectively. Independent of each other, the presence of a translocation at the time of diagnosis was associated with decreased odds of cytogenetic evolution during follow up (OR 0.39, 95% CI 0.24 - 0.63, p < 0.001) while the presence of at least one trisomy or tetrasomy at the time of diagnosis was associated with increased odds (OR 2.53, 95% CI 1.37 - 4.70, p = 0.003). A greater proportion of patients presenting with a hyperdiploid karyotype experienced cytogenetic evolution during follow up. Those patients more frequently evolved additional trisomies and tetrasomies, while translocations were more common in those presenting with a non-hyperdiploid karyotype (Table 1). The development of additional abnormalities during the three years following diagnosis (compared to no new abnormalities) was associated with increased subsequent mortality in those who survived at least three years (HR 3.22, 95% CI 1.82 - 5.68, p < 0.001). Including the time between first and last cytogenetic evaluation as a covariate did not significantly change the parameter estimates or improve model fit (p = 0.727). Conclusions: Demographics, risk profile, and overall survival of this cohort reflect the fact that patients had to survive long enough to undergo repeated cytogenetic evaluation. Hyperdiploid and non-hyperdiploid genotypes were associated with distinct behavior regarding cytogenetic evolution during follow up. The identification of cytogenetic evolution was an adverse prognostic factor in those who survived at least three years after diagnosis. These findings emphasize the importance of the dynamics of the underlying clonal disease process for accurate risk assessment and suggest that selected subgroups of patients may benefit from risk stratification during follow up. Table 1. Cytogenetic evolution during follow up in 433 patients with multiple myeloma stratified by karyotype at the time of diagnosis Hyperdiploid (n = 150) Non-hyperdiploid (n = 283) p New abnormality 76 (51%) 108 (38%) 0.012 New monosomy 8 (5%) 24 (8%) 0.243 New trisomy 48 (32%) 55 (19%) 0.004 New tetrasomy 37 (25%) 27 (10%) < 0.001 New deletion 17 (11%) 27 (10%) 0.557 New translocation 1 (1%) 11 (4%) 0.065 Most common new abnormality [type (percent of type in each group)] Monosomy mono(13) (75%) mono(13) (62%) Trisomy tri(11) (22%) tri(3) (22%) Tetrasomy tetra(15) (48%) tetra(15) (30%) Deletion del(17p) (79%) del(17p) (63%) Translocation t(11;14) (100%) t(11;14) (36%) Data are given as count (percent) unless denoted otherwise. Disclosures Binder: American Society of Hematology: Research Funding. Kumar:AbbVie: Research Funding; Onyx: Research Funding; Sanofi: Research Funding; Celgene, Millenium, Sanofi, Skyline, BMS, Onyx, Noxxon,: Other: Consultant, no compensation,; Skyline, Noxxon: Honoraria; Millenium/Takeda: Research Funding; Janssen: Research Funding; Celgene: Research Funding.

Abstract Abstract 1958 Vaccines may offer additional benefit as consolidation therapy after plateau phase or autologous stem cell transplant (ASCT) for multiple myeloma (MM). We have reported previously the results of another phase II trial showing that using APC8020 (Mylovenge™) after ASCT improved the overall survival (OS 5.3 yrs, 95% CI 4.0 yrs – NA) compared to ASCT alone (3.4 yrs, 95% CI 2.7 – 4.6 yrs; p = 0.02; Lacy, AJH (84): 799). We now report the results from a randomized, phase II trial using the same vaccine plus adjuvant cytokines in MM patients in plateau phase after either chemotherapy or ASCT. Twenty patients were enrolled between 2001 and 2003 and were randomized to receive APC8020 and adjuvant cytokine of either interferon-g (IFNg, arm A, n = 10) or interleukin-2 (IL2, arm B, n = 10). Each cycle of treatment included five days of daily subcutaneous injections of either IFNg (106 IU, arm A) or IL2 (200 mg, arm B) followed by APC8020 injection. Each patient received a cycle of treatment every 2 weeks for 4 cycles. One patient in each arm was in plateau phase post-chemotherapy. Time from diagnosis to treatment was 11.9 mos for the patient in arm A and 16.2 mos for arm B. Time to progression (TTP) was 3.7 and 68 months respectively the patient in arm A and B. Both patients were alive at five years. For the 9 post-ASCT patients in each arm, no statistically significant differences were seen in the baseline characteristics between the 2 arms. The median time from diagnosis to treatment was 15.4 months. No grade 4 or 5 adverse events (AEs) were reported. Two patients in each arm had grade 3 AE, including lymphopenia, thrombocytopenia, hemorrhage, infection, and fatigue. One patient in arm B had grade 3 autoimmune disorder that was deemed possibly related to study treatment. The most common AEs were grade 1 fatigue (n = 7) and anemia (n = 5) in arm A and grade 1 anemia (n = 7) and injection site reaction (n = 5) in arm B. The median TTP was 9.3 months (95% CI: 3.9 – 19.3 months) for arm A and 6.6 months for arm B (95% CI: 6.3 – 29.6 months) with no statistically significant difference between the two arms (p = 0.89). The median OS had not been reached for either arm; the 5-year OS rate was 67% and 56% for arms A and B respectively (p = 1.0). Interestingly, similar to our previous study where TTP was not different while OS was improved with vaccine, when we compared the clinical outcome for all patients in this vaccine trial to that of 78 matched control patients who only received ASCT during the same time frame, we did not see significant improvement in TTP (Figure 1). However, the 5-year overall survival for all patients in this trial is significantly improved at 71% (95%CI: 51–96%) compared to ASCT control patients (41%, 95% CI: 31 – 54%; p = 0.03; Figure 1). This trial suggests improved OS with vaccine plus cytokine. It is possible that modulation of patients’ immunity may help them live longer with multiple myeloma. Further investigation is needed to compare the approach in this trial with dendritic cell vaccine alone to better understand optimal strategy for vaccine therapy in MM. Figure 1. Kaplan-Meier curves for time to progression and overall survival Figure 1. Kaplan-Meier curves for time to progression and overall survival Disclosures: Dispenzieri: Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding. Lacy:Celgene: Research Funding.

Abstract Abstract 3557 Introduction: Autologous stem cell transplantation for patients with amyloidosis results in high reported hematologic and organ response rates compared with conventional chemotherapy. Patients: Four-hundred and thirty-four patients have undergone transplantation between March 8, 1996, and April 13, 2010 Table 1. Clinical parameters seen in patients with amyloid are given in Table 2. The overall day-100 mortality seen in this group of patients is 44 of 434 patients (10%). Results: The most important determinant of outcome is stage defined by BNP and troponin levels. Figure 1 demonstrates the survival for patients for all 3 cardiac stages. Troponin <.035; NT-proBNP <332. Stage 1 both low, Stage 3 both elevated. The survival of all patients based on whether they achieved a complete response, a partial response (>50%), or no response was analyzed. Median survival has not been reached for the complete response group, is 107 months for the partial response group, and is 32 months for the no response group (p<0.0001). Figure 2, divides the patients at the median dFLC level of 13.5 mg/dL demonstrating that for patients with a higher level of free light chain, the median survival is 87.6 months and has not been reached for those with a lower level of free light chain. A proportional hazards model for variables that impact on survival was done in all patients, and the only relevant predictor of outcome was stage (p<0.0001). When the same analysis was performed using a landmark of 6 months, the only predictor of outcome was stage (p=0.0005). When best response was incorporated into the landmark model, it was the strongest predictor of survival. The amyloid stage predicted survival (p= 0.0005), and the best response to therapy (p <0.0001). When the same analysis was performed in the entire group of 434, stage and best response each remained significant (p<0.0001). Discussion: There is a high response rate associated with high-dose therapy that was not observed in the melphalan and prednisone era. For eligible patients who can be transplanted safely, high-dose melphalan is an effective therapy for many patients with amyloidosis. Best response and stage at diagnosis are the best predictors of overall survival. Disclosures: Lacy: Celgene: Research Funding. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

Abstract Abstract 1893 Background: Recent data has shown that the level of immunoglobulin free light chain (FLC) is a prognostic factor for patients with AL amyloidosis. Approximately 25% of patients with AL amyloidosis have coexistent multiple myeloma (MM) with myeloma-related end-organ damage and patients may also present with 310% plasma cells (PC) in the bone marrow (BM) in the absence of any MM features. The goal of this study was to determine the effect of increased BM plasmacytosis in the absence of MM end-organ damage on early mortality. Methods: We performed a retrospective study of 263 consecutive patients with AL amyloidosis seen at Mayo Clinic within 30 days of diagnosis from July 2002 – April 2009, to compare the effect of PC burden among those who died within 90 days of diagnosis (n=88) and those who survived more than 90 days after diagnosis (n=175). Only those patients with documented BM PC were included in this study. MM end-organ damage was defined according to the CRAB criteria. Results: In those who died <90 days after diagnosis and patients who lived beyond 90 days, the proportion of patients with 310% BM PC were 57% and 55%, respectively. Overall survival (OS) was significantly shorter in the early mortality group when there was 310% BM PC present at diagnosis (25 vs. 54 days, p=0.006), but this was not observed in the group who survived beyond 90 days (Figure 1). In patients with 310% BM PC, troponin-T, ejection fraction (EF), and hemoglobin (Hgb) were significantly worse in the early mortality cohort but patients who survived beyond 90 days had significant increase in intraventricular septal (IVS) thickness and beta-2 microglobulin (Table 1). As expected, patients with 310% BM PC in both cohorts had significantly higher serum M-spike and involved FLC (Table). The same cohort of patients were analyzed substituting MM-related end-organ damage for 310% BM PC and similar results were observed with the exception of uric acid and calcium being significantly higher in the early mortality cohort with MM (results not shown). Conclusion: This study demonstrated that an excess of early—but not late—deaths occur in AL amyloidosis patients with 310% BM PC at diagnosis. In our cohort, this finding can be attributed to higher troponin-T levels, indicating more severe cardiac involvement as observed by worse cardiac function. These findings warrant additional investigation. Disclosures: Lacy: Celgene: Research Funding. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria.

Abstract Background: Light chain Amyloidosis (AL) is characterized by deposition of light chain derived amyloid fibrils in major organs and/or soft tissue. An observational study on natural history and outcome of localized immunoglobulin light-chain amyloidosis without vital organ (liver, heart, kidney, peripheral and autonomic nervous system) involvement has shown extremely low rate of progression (1%) to systemic amyloidosis at a median follow-up of 74.4 months (Mahmood S et al. The Lancet Haematology; 2015; 6:e241-e250). There is, however, limited evidence in published literature on natural history of AL amyloidosis confined to fat and/or bone marrow biopsy, without involvement of vital organs or other soft tissues. Methods: We retrospectively identified patients with AL amyloidosis limited to fat and/or bone marrow aspirate in a single-institution database. Patients were evaluated for progression to systemic amyloidosis. Statistical analysis was done using JMP 10.0.0 (SAS Institute Inc.). Results: We identified 117 patients, with a median age of 70 years, who had light chain amyloidosis detected in abdominal fat aspirate and/or bone marrow biopsy, without systemic involvement. Amyloid was seen in fat only in 39%, marrow only in 54% and in both sites in 7%. The median follow up was 45.6 months (95% CI-38.1-57.7) from detection of amyloid. Of these, 64% were alive at the time of analysis. Among 117 patients, 65 were treated for a diagnosis of another plasma cell disorder made prior to or concurrent with detection of amyloid. The remaining 52 patients only had isolated fat or marrow amyloid. Among 65 patients with another diagnosis of plasma cell disorder requiring treatment, 3 progressed to systemic amyloidosis, one each with cardiac, renal and lymph node (LN) involvement detected at 32, 42 and 65 months respectively from the detection of amyloid. The first 2 patients had underlying multiple myeloma, and the third patient with LN involvement had underlying Waldenström macroglobulinemia. Among 52 patients without another diagnosis of a plasma cell disorder requiring treatment, at a median follow up of 32 months, no progression to systemic amyloidosis was observed. Median overall survival (OS) in 117 patients from detection of amyloid, using Kaplan-Meier survival estimates, was 60.2 months (95% CI-48.9-146.1). Conclusion: Our study highlights the fact that isolated amyloidosis detected in fat and/or bone marrow aspirate, in the absence of another plasma cell dyscrasias that require therapy, is unlikely to progress to systemic amyloidosis. Watchful waiting might be considered in such patients after a thorough evaluation to rule out systemic involvement. Disclosures Gertz: Smith Kline: Honoraria; Novartis: Honoraria; Onyx: Honoraria; millenium: Consultancy, Honoraria; Celgene: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Abbvie: Research Funding; Millenium: Consultancy, Research Funding; Novartis: Research Funding; Onyx: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding.

Abstract Abstract 2970 Background: Over a quarter of patients (pts) with symptomatic multiple myeloma (MM) have some degree of renal insufficiency at the time of diagnosis. Multiple studies show that presence of renal failure is strong predictor of inferior overall survival in MM. With effective therapy, renal function improves in a considerable number of patients. It is not clear if the return of renal function to normal levels will improve their outcome to that expected for patients without renal dysfunction. Methods: We evaluated 1478 patients with newly diagnosed myeloma seen at Mayo Clinic within 90 days of diagnosis, between January 1999 and January 2009. We examined these patients for improvement in renal function and identified the lowest serum creatinine obtained during the disease course. The outcomes were analyzed with respect to the renal function improvements. Results: The median age at diagnosis was 64 years (range; 22–93) and 50% were male. The median estimated follow up for the entire cohort was 53 months, with 781 patients alive at the time of analysis with a median follow of 3 years. The serum creatinine was over 1.5 mg/dL at diagnosis in 333 (22.5%) pts and over 2.5 mg/dL in 148 (10%) pts. The median overall survival for the 333 patients was 37 mos (95% CI; 28, 40) compared to 56 mos (95% CI; 51, 63) for those < 1.5 mg/dL; P < 0.001. Among the 333 pts with baseline Cr > 1.5 mg/dl, any improvement in Cr was seen in 263 (79%) including an improvement of at least 0.5 mg/dL in 208 (62%) pts. Among the 263 pts with any improvement, the median time to lowest Cr was 4 months (range; 1–13). The median survival of the group of patients with Cr <= 1.5 mg/dl, over 1.5 mg/dL at diagnosis but improved to <= 1.5 mg/dL, or remained >1.5 mg/dL were 56., 40 and 27 mos respectively; P < 0.001, Figure). We then examined the impact of renal function improvement in the group of patients where the baseline Cr was >2.5 mg/dL. The median OS for the 42 (out of 148 pts with Cr > 2.5 at diagnosis) who had improved to <=1.5 mg/dL was 40 mos compared to 56 mos for those with a Cr <= 1.5 mg/dL at diagnosis and 27.4 mos for the 106 pts whose Cr did not decrease to <= 1.5 mg/dL; P < 0.001. Conclusion: The results of this study point toward improved outcome among patients with renal dysfunction in whom renal function improves. However, it shows that this improvement in renal function does not necessarily improve survival to that observed for the patients with a comparable level of serum creatinine at diagnosis. While early treatment of asymptomatic myeloma has been shown to have little impact on overall survival, a strategy of waiting for serious features of target organ damage to appear before initiation of treatment may have a negative impact on survival in some patients, especially patients with high light chain production who have a higher predilection for renal insufficiency. Disclosures: Kumar: Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding. Off Label Use: Lenalidomide for treatment of newly diagnosed myeloma. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Lacy:Celgene: Research Funding.