Citations

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 Background: Dexamethasone (dex) is an integral part of various anti-myeloma regimens both in the frontline and relapsed/refractory (RR) setting. Several clinical trials have shown that dex adds to the efficacy of novel therapeutic agents for multiple myeloma (MM). Yet, a substantial number of patients are intolerant to even the standard of care low-dose dex (40 mg weekly), especially in heavily pre-treated RRMM, possibly due to cumulative steroid toxicities and thus, require dex dose adjustments. There is a concern of compromising the efficacy of anti-MM regimens by adjusting the dex dose lower. We describe the frequency of dex dose adjustment, characteristics of patients who required it and its effect on patient outcomes in a large prospective clinical trial of pomalidomide (pom) and dex in RRMM (MC0789). Methods: We utilized data from the Pom-dex trial (MC0789), which treated RRMM patients in different cohorts of pom (2 vs. 4 mg; 21 vs 28 days cycle) with fixed dose dex (40 mg orally weekly). Patients were divided into 2 subgroups, with any dose adjustment/elimination of dex vs. not. Continuous and categorical variables were compared between the two groups using two-sample t-test/Wilcoxon rank sum test or Chi-squared test, respectively. Logistic regression and Cox regression models were used to find the univariate and stepwise multivariate predictors of response to treatment and overall mortality, respectively. Kaplan-Meier method was used to estimate overall survival (OS) at 1, 3, and 5 years. All statistical tests were two-sided with the alpha level set at 0.05 for statistical significance. Results: Results from the MC0789 clinical trial have been reported previously. Almost half of all treated patients in this trial had dex dose adjusted (n=175/343; 51%). The median number of cycles for the first dose adjustment in this group was 3 (range 1-62), with 46.5% of patients (n=82) having multiple dose adjustments and majority (58.3%, n=102) within the first 3 cycles of treatment. Patients in the dose adjustment group were significantly older (mean 65 vs 60 years; p=0.0001). Males, Whites and patients diagnosed before 2006 or with normal cytogenetics also had a higher incidence of dex dose adjustment, though this was not statistically significant. Patients with dex dose adjustment had a longer duration of treatment (mean 339 days) as compared to the non-adjusted cohort (mean 123.65 days) (95% CI 160.13, 270.58; p <0.0001). Dex dose adjustment was associated with a higher probability of responding in the clinical trial after a univariate (p<0.001) as well as multivariate (p<0.001) analysis. Patients with dex dose adjustment also had a significantly better OS at 1, 3 and 5 years by univariate (p<0.001) and multivariate (p<0.001) analysis. (Figure 1) The only other significant factor was lesser number of prior regimens (3 or less), associated with a higher probability of response (p=0.002) and survival (p<0.001). Conclusion: Our analysis established that in these heavily pre-treated RRMM patients, appropriate dose adjustment of dex did not compromise their response rates; patients remained on treatment significantly longer and had an improved survival. Majority of patients (58.3%) requiring dex dose adjustment had it instituted early during treatment (<3 cycles), suggesting that early disease progression was less likely to determine dex dose continuation or adjustment. Appropriate dex adjustments should be judiciously employed as they may ensure longer treatment duration with novel anti-MM therapeutic agents, conferring superior response and survival in this difficult to treat MM subgroup. This also paves the path to further optimize dex dose in various anti-MM regimens, especially in these patients who are more likely to be intolerant to it. Disclosures Kumar: Skyline, Noxxon: Honoraria; Celgene, Millennium, Onyx, Janssen, Noxxon, Sanofi, BMS, Skyline: Consultancy; Celgene, Millennium, Onyx, Novartis, Janssen, Sanofi: 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.

Abstract Abstract 3053 Background: Patients with smoldering multiple myeloma (SMM) have a higher chance of progression to active MM than patients with monoclonal gammopathy of undetermined significance (MGUS). Since active MM remains incurable and since patients with SMM can have a long time to requiring treatment, observation remains an option for these patients. Bisphosphonates can prevent the bone complications of myeloma. The immunomodulatory (IMiD) drugs are well-tolerated and have documented anti-tumor activity in active MM. We hypothesized that treatment with the IMiD THAL and a bisphosphonate (ZLD) would prolong the time to progression (TTP) over the control arm of ZLD alone. This is the first report of this phase III trial of THAL/ZLD vs ZLD alone for patients with untreated SMM. Goals: The primary goal of this trial was to compare the TTP between patients treated with THAL/ZLD versus ZLD alone in asymptomatic MM. Secondary goals were progression rate at one year, response rate, duration of response, time to next therapy, and toxicity. Methods: Patients were required to have measurable disease as defined by either a serum monoclonal protein >1.0 g by protein electrophoresis or nephelometry or >200 mg of monoclonal protein in the urine on 24 hour electrophoresis or a measurable soft tissue plasmacytoma; >10% plasma cells as measured on the bone marrow aspirate, bone marrow biopsy, or labeling index; absolute neutrophil count >1500/μL; platelet count >100,000/μL; creatinine <2.0 mg/dL, and a performance status of 0, 1, or 2. Patients could not have symptomatic MM that required chemotherapy. The statistical plan was to accrue 120 eligible patients (60 per arm) over 4 years and after a minimum follow-up of 12 months the study would provide >90% power at a type I error rate of 0.05 to detect an increase in the median TTP from 12 months (ZLD) to 24 months (THAL/ZLD), and >80% power to detect an increase in median TTP from 12 to 21 months). Results: The study was activated in July 2003 and closed March 2009 due to slow accrual. Sixty-eight patients (35 Thal/ZLD; 33 ZLD) with a median age 63 years (range, 47–84) were randomized. The median TTP for Thal/ZLD versus ZLD was 2.4 years versus 1.2 years, respectively, P=0.02 one-sided log-rank. After adjusting for pre-specified stratification factors, the hazard ratio for TTP was 2.2 (one-sided p value = 0.01, univariate stratified Cox PH model) for ZLD compared to Thal/ZLD. 89% of patients on the Thal/ZLD arm were progression-free survival (PFS) at one year compared to 55% on ZLD alone (one-sided p<0.001, chi-square). Similar results were obtained (Table and Figures) when the CRAB (calcium, renal, anemia, bone) criteria were applied. Confirmed response was evaluated using the first 12 months of treatment. In the Thal/ZLD arm the response rate was 31% with a median duration of response of 5.1 years (95% CI: 1.9 - NA). There were no confirmed responses in the ZLD alone arm. The median overall survival has not been reached for either arm. In regards to toxicity, no grade 5 adverse events (AEs) have been reported. Thirty patients have reported grade 3+ AEs (17 Thal/ZLD; 13 ZLD, Fisher's exact p-value 0.47). Eight patients have reported grade 4 adverse events (5 Thal/ZLD; 3 ZLD, Fisher's exact p-value 0.71). Overall, only one grade 4 event was felt to be at least possibly related to study treatment – grade 4 neutropenia in Thal/ZLD. Conclusions: While the trial did not meet its planned accrual goals, there was a significant improvement in improved in outcomes in the Thal/ZLD arm compared to control (ZLD). Thal/ZLD produces anti-tumor responses that are quite durable with the median response duration of over 5 years. ZLD alone did not produce any anti-tumor responses. This study indicates that a non-chemotherapy approach can be effective in SMM and may be a useful strategy to test in future studies. Disclosures: Off Label Use: Thalidomide for smoldering myeloma. 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. Gertz:Celgene: Honoraria; Millennium: Honoraria.

Abstract Background: Amyloidosis is a multisystem disease with extracellular deposition of pathological insoluble beta-fibrillar proteins. Involvement of the heart is seen in more than one-half of the patients with systemic AL amyloidosis and it is the most important determinant of clinical outcome. Cardiac amyloidosis is a restrictive infiltrative cardiomyopathy in which, despite declines in stroke volume that accompany disease progression, the ejection fraction (EF) often remains preserved even in advanced stages of the disease. King et al. proposed a novel index of myocardial function, the myocardial contraction fraction (MCF), defined as the ratio of stroke volume (SV) to myocardial volume (MV). MCF is a measure of myocardial shortening, which differentiated myocardial performance in patients with similar degrees of hypertrophy and in a recent small cohort of AL amyloidosis patients appeared superior to left ventricular ejection fraction (EF) in predicting overall survival (OS). It was our goal to assess the prognostic role of MCF in a large cohort of patients with AL amyloidosis in the context of other prognostic variables. Methods: Patients seen between 4/1/1999 and 2/1/2015 were eligible for this retrospective study if they had an ECHO at the Mayo Clinic, Rochester, MN within 30 days of their AL amyloidosis diagnosis with measurements of left ventricular chamber size and wall thickness needed to calculate MCF, EF, and the presence or absence of pericardial effusion. To capture the full cohort, modeling was done first excluding Mayo (2012) staging and global averaged left ventricular longitudinal peak systolic strain (LV strain) since limited numbers of patients had these studies, 342 and 294, respectively. Thresholds of continuous variables were chosen based on receiver operator curves targeting death at 1-year. Cox proportional hazards analysis was used to identify factors that were prognostic for OS. Statistical analyses were done using JMP 9.0 (SAS, Cary, NC). Results: Among the 722 patients satisfying entry criteria,median age was 64 years (range 32-94) and 66% were male. The best cutoff for MCF was 21% (sensitivity: 74%, specificity: 60%; AUC=0.699) and distinguished two groups with different OS (median 53 vs. 9 months, P<0.0001; Figure). On univariate analysis the baseline ECHO variables predicting OS were interventricular septum thickness (IVS) >12 mm (RR 1.8, P=0.0002), EF <60% (RR 1.7), MCF ≤21% (RR 2.1), and presence of pericardial effusion (RR 2.0), all with P<0.0001. On multivariate MCF ≤21% (RR 1.6, P <0.0001), EF <60% (RR 1.4, P=0.0007) and the presence of pericardial effusion (RR 1.3, P=0.002) were independent predictors of OS. Additional modeling was done with the subset of 342 patients who were assessable for Mayo (2012) staging, (i.e. measurements of immunoglobulin free light chain, NT-proBNP, and troponin T). On univariate analysis, patients with a Mayo (2012) stage ≥ 3 had a RR 2.1, p<0.0001. On multivariate, only MCF ≤21% (RR 1.5, P =0.01), Mayo (2012) stage ≥ 3 (RR 1.5, P=0.01) and EF<60% (RR 1.7, P=0.0006) were independent prognostic determinants. Finally, we addressed LV-strain among the 294 patients in whom the study was performed. There was a significant correlation between MCF and LV strain (rho =-0.86, P<0.0001). On univariate, LV-strain less negative than -13 generated a RR of 2.3, p<0.0001. In contrast to the model containing MCF, on LV-strain multivariate, EF was no longer significant, but LV-strain less negative than -13 (RR 2.0, P=0.008) and Mayo (2012) stage ≥ 3 (RR 2.0, P=0.008) predicted independently OS. Conclusions: MCF ≤21% identified a subgroup of patients with a high mortality risk, and it was independent of the Mayo (2012) staging but highly correlated with LV strain. An advantage of MCF, which is a novel volumetric measurement of the left ventricular chamber, is that, unlike LV-strain, MCF is simple to calculate from routine ECHO measures. Figure 1. Overall survival of 722 patients according to MCF<21%. Figure 1. Overall survival of 722 patients according to MCF<21%. Disclosures Kumar: AbbVie: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Skyline, Noxxon: Honoraria; Celgene, Millenium, Sanofi, Skyline, BMS, Onyx, Noxxon,: Other: Consultant, no compensation,; Sanofi: Research Funding; Millenium/Takeda: Research Funding; Onyx: Research Funding.

Abstract Abstract 2253 Background: Lenalidomide based combinations are among the most common initial therapies for myeloma. Previous studies have suggested that lenalidomide therapy can result in suboptimal stem cell collection in patients eligible to undergo autologous stem cell transplantation, especially older patients after prolonged exposure to the drug. Many salvage approaches are used when attempting repeat stem cell collection in this patient group. Patients and Methods: Two hundred twenty four patients who underwent stem cell collection following lenalidomide-dexamethasone induction from July 2004 and December 2009 were included in the current analysis. Data pertaining to the duration of lenalidomide therapy, stem cell mobilization regimen, and the collection yields were collected from the medical records. Results: The median age at mobilization was 60.6 years (range; 29, 76) and 136 (60%) were male. There were a total of 245 collection attempts from among 224 patients, 21 (9.8%) patients attempting to remobilize after failing to collect the desired numbers of stem cells at the first attempt. We first analyzed the results of the initial collection attempt. The median duration of lenalidomide therapy prior to stem cell collection was 4 months (range; 1, 26). The mobilization strategies were GCSF (Granulocyte Colony Stimulating Factor) alone in 151 (67%) patients, cyclophosphamide (CTX) followed by GCSF in 29 (13%) patients, and GCSF plus AMD3100 in 44 (20%) patients. Among those receiving AMD3100, it was added either due to peripheral blood CD34 cell count not reaching the threshold for initiation of harvest or for poor first day CD34 cells collection in 34 patients and given in a planned fashion in 10 patients. Overall 15 patients (7%) failed to reach the peripheral CD34 cell counts required to initiate apheresis, and among those starting apheresis 6 patients failed to collect at least 2 million CD34 cells/kg; a cumulative failure rate of 9%. Another 18 (8%) patients failed to collect at least 4 million CD34 cells /kg. The CD34 cells yield on day 1, the total yield, number of collections, the average daily yield and the percentage of the targeted cells collected for each mobilization strategy including failure rates are detailed in the table. Twenty-one patients reattempted stem cell mobilization; including 14 that failed a first attempt and 7 did who not achieve the intended goal even though they collected more than 2 million CD34 cells/kg. The mobilization regimens were GCSF alone, CTX + GCSF, GCSF + GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) and GCSF + AMD in 5, 8, 3, and 4 patients respectively. All patients collected at least 2 million CD34 cells /kg and 14 patients (70%) collected more than 4 million CD34 cells /kg. The median CD34 cells collected with the second attempt was 5.4 million/kg (rang; 2, 19.5) bringing the median total collection for these 21 patients to 9.6 million/kg (2.6-19.6). Overall, of the 224 patients studied, all but the 6 patients who failed initially and did not attempt a second collection collected at least 2 million CD34 cells /kg and 197 (88%) collected at least 4 million CD34 cells/kg. Conclusion: While the overall failure rate of stem cell collection in patients receiving initial therapy with lenalidomide is 10%, a risk adapted approach of adding AMD3100 appear to decrease the risk of failure. However, majority of patients failing a stem cell harvest attempt can be salvaged with a second collection allowing these patients to proceed to a stem cell transplant if desired. Disclosures: Gertz: Celgene: Honoraria; Millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genzyme: Research Funding. Lacy: Celgene: Research Funding. Dispenzieri: Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Micallef: Genzyme: Membership on an entity's Board of Directors or advisory committees. Kumar: Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

Abstract Abstract 1965 Background: Pomalidomide is an immunomodulatory compound to be used for heavily pre-treated patients with relapse and refractory multiple myeloma and has shown considerable efficacy in recent clinical trials. It is not clear how patients may respond to other therapies, once the disease becomes refractory to pomalidomide. We examined this question among a cohort of patients receiving pomalidomide therapy in phase 2 clinical trials. Methods: Patients enrolled in an ongoing phase 2 clinical trial of pomalidomide (2-4 mg daily) along with dexamethasone (40 mg weekly), in relapsed myeloma, form the study population. Several cohorts of patients (>= 3 prior therapies not specified, lenalidomide refractory, and lenalidomide and bortezomib refractory patients were enrolled sequentially in this trial (Lacy, M.Q., et al., J Clin Oncol, 2009. 27(30): p.5008–14). Only those patients who have gone off study for disease progression were included in the current analysis. Details of subsequent therapies and survival data were obtained from the medical records. Results: Forty-seven patients from among 142 patients enrolled on the clinical trial between November, 2007 and April, 2010 were included in the study. The median (range) duration of pomalidomide therapy was 4 (0.6-16) months. 15 (32%) patients were lenalidomide refractory and 11 (23%) were refractory to both lenalidomide and bortezomib at the time of study entry. The best confirmed response to pomalidomide was MR (Minimal Response) or better in 23 patients (52%). Various regimens were employed following relapse on pomalidomide. The response to the first regimen following relapse in the 34 patients where salvage therapy was initiated is as shown in Table 1. Overall, 81 regimens were employed across 34 patients; median (range) number of regimens per patients was 1 (0-8). The response rates to the different regimens were as shown in the Table 1. The median overall survival (OS) from the time of progression on pomalidomide was 14.7 months (95% CI; 4, NR). The OS was similar between those patients who had a response to pomalidomide (MR or better) and those who did not. However the OS was shorter for patients who were refractory to lenalidomide and bortezomib (2.1 months) compared to those who were lenalidomide refractory only (6.5 months), and the non-refractory group (NR), P=0.06. Conclusions: This study confirms poor outcome of the patients relapsing after all available therapies. It also gives interesting insights into the activity of different regimens among patients who have relapsed after pomalidomide. The findings once again highlight the incurable nature of the disease and warrant further investigation to develop newer effective treatment regimens for this group of patients who presently do not have effective therapeutic options especially in the relapsed setting. Regimens: ASCT: Autologous Stem Cell Transplantation, Bz: Bortezomib, Mel=Melphalan, Dex: Dexamethasone, CRD: Cyclophosphamide, Revlimid (Lenalidomide), Dexamethasone, CTX; Cyclophosphamide, Len; Lenalidomide, Sor: Sorafenib, VDT-PACE: Velcade (Bortezomib), Dexamethasone, Thalidomide, Cisplatin, Adriamycin, Cyclophosphamide, Etoposide. Response: SD; Stable Disease; Prog; Progression MR: Minimal Response; PR: Partial Response. Disclosures: Kumar: Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding. Mikhael:Celgene: Research Funding; Onyx: Research Funding; Novartis: Research Funding. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria.