Hogan, William J.

Abstract Abstract 460 Background: CYT387 is a potent JAK-1/2 inhibitor that suppresses the in vitro growth of cells harboring JAK2V617F (Leukemia 2009;23:1441) and was effective in a murine model of myeloproliferative neoplasms (MPN) (Blood 2010;115:5232). Aims/Methods: To assess the safety, tolerability, and pharmacokinetic behavior of CYT387 in a Phase I dose-escalation study in patients with high- or intermediate-risk primary myelofibrosis (PMF) and post-PV or post-essential thrombocythemia (ET) myelofibrosis. The secondary objective was evaluation of preliminary efficacy. CYT387 was administered orally once daily in 28-day cycles. Once dose-limiting toxicity (DLT) was identified, a dose-confirmation cohort initiated treatment at the maximum tolerated dose (MTD) or lower. Result: Thirty six subjects (median age 64 years) have been enrolled (targeted accrual 120); 18 each in the dose escalation and dose confirmation phases. Twenty-three subjects had PMF, 8 post-PV MF, and 5 post-ET MF; 81% were JAK2V617F-positive. Median palpable spleen size was 18 cm and 20 subjects (56%) were red cell transfusion-dependent at study entry. Prior treatment included JAK inhibitors (9 and 1 subjects with INCB018424 and TG101348, respectively) and pomalidomide in 9 patients. The median treatment duration to date is 15 weeks (range 4–38). Dose-linear plasma exposures were observed up to 300 mg/day, with mean elimination T1/2 at steady state ranging from 3.9 to 5 hours across doses. Toxicity: All 36 subjects were evaluable for toxicity. At 400 mg/day, 2 of 6 subjects experienced DLT (1 each with asymptomatic grade 3 hyperlipasemia and grade 3 headache that were reversible upon holding drug); consequently, the MTD was declared at 300 mg/day. In the dose-confirmation phase, subjects were started at one of 2 dose levels that were deemed clinically effective: 150 mg/day (n=15) and 300 mg/day (n=3). Thirty-five subjects are currently on active therapy: 100 mg/day (n=2), 150 mg/day (n=20), 300 mg/day (n=10), and 400 mg/day (n=3). CYT387 was well tolerated. No grade 4 non-hematological toxicities were observed. Grade 3 non-hematologic adverse events were infrequent and included increased transaminases (n=2), increased alkaline phosphatase (n=2), headache/head pressure (n=2), increased lipase (n=1), and QTc prolongation (n=1). Thirteen (36%) subjects experienced “first-dose effect” characterized by grade 1 lightheadedness and hypotension; this phenomenon was self-limited and generally resolved within 3–4 hours with rare recurrence. Grade 3/4 thrombocytopenia was seen in 8 (22%) subjects, and treatment-emergent grade 3 anemia was seen in 1 subject only (3%). Treatment-emergent grade 3/4 neutropenia was not observed. Efficacy: Thirty two of 36 subjects who completed at least 1 cycle were eligible for response assessment: Anemia: Twenty two subjects were evaluable for anemia response (baseline Hgb <10 g/dL or red cell transfusion-dependent). Of these, 9 subjects (41%) achieved the threshold of response for “Clinical Improvement (CI)” per the International Working Group for MPN Research and Treatment (IWG-MRT) criteria, including 2 of 4 subjects who were previously treated with INCB018424. An additional 5 subjects experienced a >50% reduction in transfusion requirement, thus increasing the total anemia response rate to 63%. Splenomegaly: Thirty of 32 evaluable subjects had splenomegaly at baseline: median 20 cm; range 10–32 cm. Twenty nine subjects (97%) had some degree of spleen size reduction (median 9 cm; range 2–18 cm): 11 (37%) patients have achieved a minimum 50% decrease in palpable spleen size, thus qualifying them for a CI, including 3 of 8 subjects (38%) who were previously treated with INCB018424. Constitutional symptoms: The proportion of patients with the following symptoms at baseline, are: fatigue (97%), pruritus (22%), night sweats (38%), cough (13%), bone pain (28%), and fever (16%). At last follow up, improvement (complete resolution) in these symptoms was reported by 68% (16%), 86% (57%), 83% (75%), 75% (50%), 78% (44%), and 100% (100%), respectively. Conclusion: CYT387 is first-in-class of the JAK inhibitors with a significant response rate in anemia in myelofibrosis patients. The drug also shows substantial activity in reducing spleen size and controlling constitutional symptoms. CYT387 is well tolerated, and treatment responses have been seen both at (300 mg/day) and below (150 mg/day) the MTD. Disclosures: Pardanani: Cytopia Inc.: Research Funding. Off Label Use: Clinical trial data for CYT387 use in Myelofibrosis. Fida:YM Biosciences Australia: Employment, Equity Ownership. Burns:YM Biosciences Australia: Employment, Equity Ownership. Smith: YM Biosciences Australia: Employment, Equity Ownership.

Abstract Abstract 2525 Background: Patients with relapsed AML have a very poor outcome. The molecular signature at diagnosis has emerged as a significant marker for prognostic, and possibly therapeutic, values in newly-diagnosed AML. FLT3 mutations are found in about 25–30% of AML pts. In the absence of FDA-approved agents for FLT3, the prognostic value of FLT3 mutation on clinical outcome for relapsed AML (rAML) is not well documented. Aim: To study clinical implications of FLT3 status on rAML. Methods: All adult pts with AML diagnosed and treated at Mayo Clinic between 2003–2011were studied. Retrospective data collection included pts' demographics, laboratory tests, bone marrow biopsies, FLT3 mutation (internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutation), and survival information. IRB approval was obtained in accordance with Helsinki declaration. Chi-Square and T-test were used for comparatives between groups and Kaplan-Meier test was applied for survival estimates using JMP 9.0 software. Results: A total of 192 pts with newly-diagnosed with AML were identified. Sixty percent (115) were males, 88% (168) were Caucasians, 26% (49) had antecedent hematological disease (AHD), and 13% (25) had previous exposure to chemo- or radiotherapy. Forty-seven percent had a normal chromosomal analysis, and 18% (35) had FLT3 mutation (28 ITD, 7 TKD). In FLT3-mutated pts, median WBC was 70 x109/L (p=0.0016), hemoglobin 9.5 g /dL, and platelets 48 x109/L, compared to 8.8 x109/L, 9.1 g/dL, 50 x109/L in the rest of pts, respectively. Peripheral blood blasts were elevated in FLT3-mutated group compared to rest of pts (p 0.0059). A total of 128 pts achieved complete remission (CR), with 79 (62%) subsequently relapsed. Of the relapsed patients, 93% (74) were Caucasians, 54% (43) males, 22% (17) had AHD, and 8% (6) had prior chemo- or radiotherapy. Cytogenetics were diploid in 49% (39) and complex in 15% (12). Hematopoietic stem cell transplantation was performed in 30% (24) of pts. Eleven of 79 (14%) pts were FLT3-mutated at relapse (Group 1); with 1 pt having TKD-mutation. Forty-eight percent (38) of pts had unmutated-FLT3 (Group 2), and 38% (30) pts were FLT3-unknown (Group 3). In group 1, median WBC was 9.9 x109/L, hemoglobin 10.55 g /dL, platelets 55 x109/L, compared to 3.2 x109/L (p=0.0034), 10.55 g/dL, and 58 x109/L in group 2, respectively. Peripheral blasts were significantly elevated in group 1 compared to group 2 (38% vs 4%, p <0.0001). Surprisingly, 3/11 pts (27%) with FLT3 mutation at relapse were unmutated at diagnosis. CR was achieved in 2/11 (18%) pts in group 1 compared to 15/38 (39%) in group 2 (p=0.19). Median overall survival in rAML was significantly lower in group 1 compared to group 2 (90 days vs 229 days, p 0.0076). This survival difference was statistically more significant in pts with diploid cytogenetics at relapse compared to the rest (p 0.0009 vs 0.48, respectively). Within 1.5 years, all pts in group 1 died, compared to 21% survived in group 2. Conclusion: FLT3-mutated AML pts had a significantly higher peripheral WBC and blasts at both diagnosis and relapse. Importantly, FLT3 at relapse was found to be mutated in one quarter of pts who were wild-type FLT3 at diagnosis; raising the importance of assessing FLT3 gene on all relapses. FLT3 mutation significantly predicted worse median overall survival in rAML raising the need for novel agents, such as FLT3 inhibitors, in this population. Disclosures: No relevant conflicts of interest to declare.

Abstract Background L-asparaginase (LASP) depletion of asparagine reduces antithrombin (AT) and fibrinogen and is associated with thromboembolic (TE) and hemorrhagic events (HE). AT replacement in pediatric ALL patients demonstrated safety and potential benefit as thromboprophylaxis in a prospective, randomized trial.(Mitchell et al, 2003) Current consensus supports AT replacement when AT activity is below 60%.(Stock et al, 2011) The incidence of TE and HE in adults receiving AT repletion during LASP or pegylated asparaginase (PEGASP) requires further investigation. Methods This single center, retrospective, observational study was approved by the Mayo Clinic Institutional Review Board. Consecutive adult patients with a confirmed diagnosis of ALL receiving LASP or PEGASP containing chemotherapy regimens between January 2000 and October 2012 were evaluated. Patients with documented thrombophilia and pre-existing TE or HE were excluded. Patients receiving AT concentrate (ATC) compared to those that did not and were evaluated up to 60 days after the last LASP or PEGASP dose for objectively confirmed TE and HE. Results Of the 74 patients screened, 54 (73%) met inclusion criteria. Forty-seven (87%) received ATC and were evaluable. The remaining 7 (13%) did not meet follow up duration and were excluded from further analysis. Twenty-three (49%) patients received LASP, 20 (42%) received PEGASP and 4 (9%) received both. Distribution per treatment protocols was; CALGB 9111 (n=16 (34%), Larson et al, 1998), E2993 (n=12 (25%), Goldstone et al, 2008), C10403 (n=8 (17%), NLM: NCT00558519), CCG 1941 (n=6 (13%), Gaynon et al, 2006) and Augmented HyperCVAD (n=5 (11%), Faderl et al, 2011). A total of 1465 AT activity levels were analyzed, resulting in 378 doses of ATC. Ten patients (21%) experienced a clinical event, with all events occurring during cycle 1 of chemotherapy (table 1). Median time from last LASP or PEGASP dose to TE was 13 days (range 3-56) with a median of 4 days (range 3-13) from last ATC dose to TE. Median AT activity level at time of TE was 56% (range 47-72). Thrombotic events included; line-related deep vein thrombosis (LRDVT, n=7), cerebral venous sinus thrombosis (CVST, n=1) and pulmonary embolism (PE, n=1). One patient with cerebral hemorrhage constituted the only HE. All LRDVT occurred in central venous catheters and management included; line removal (n=3), anticoagulation (n=1), line removal and anticoagulation (n=2) and no intervention (n=1). The single case of PE was managed with anticoagulation. Two patients had a recurrent LRDVT in different locations during subsequent chemotherapy in spite of ongoing ATC supplementation. Conclusions The incidence of TE in adult ALL patients receiving LASP or PEGASP during induction chemotherapy with AT thromboprophylaxis was 19%. LRDVT was the most common TE with a comparable incidence to adult ALL patients not receiving ATC (15%) (Grace et al 2011). There was a small incidence of non-LRDVT (4%) and HE (2%). As induction-phase chemotherapy and placement of central lines are independent risk factors for thrombosis, the cost-effectiveness of AT replacement for prevention of TE during adult ALL treatment requires prospective evaluation. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: International Working Group (IWG) has set criteria in 2003 for response assessment in patients with AML; at which time intensive chemotherapy was the main therapy (Cheson, JCO 2003). Hypomethylating agents (HMA) were approved shortly after for the treatment of elderly AML (Fenaux, JCO 2009; Dombret et al Blood 2015). Although few patients achieve a deep response, the majority will have stable disease (SD), some of which could last several months while patients continue to receive HMA and gain clinical benefit. We hereby describe outcomes for patients who achieve SD with HMA for the treatment of elderly unfit AML patients. Methods: A total of 56 AML patients' data from Feb 2007 to June 2015 at Mayo Clinic were reviewed after appropriate IRB approval was obtained. All cases had their bone marrow slides reviewed at our institution. Patients were considered for our study if they received HMA as frontline therapy for their AML. Patients who received HMAs after induction chemotherapy failure or for their MDS were excluded. Response was identified based on 2003 IWG AML response criteria. Patients with SD were categorized into short-lasting (<6 cycles of HMA, cohort 1) or long-lasting (≥6 cycles of HMA, cohort 2) SD.Prognostic factors were analyzed by univariate and multivariate analyses. Survival estimates were calculated using Kaplan-Meier curves and univariate and multivariate analyses was based on log-rank testing using JMP software version 10. Results: i) Characteristics: Fifty six AML patients were treated with HMA as frontline therapy with median age of 76 years (range, 59-91), 68% of which were males. Therapy related AML (T-AML) was seen in 2% of the cases. Cytogenetics were favorable risk in 2%, intermediate in 62%, and poor in 36%. Complete remission (CR) was found in 10 (18%) patients, CR with incomplete count recovery in 3 (5%), partial remission (PR) in 3 (5%) patients. Forty patients were non-responders (SD). ii) Characteristics of HMA SD cohorts: Upon comparison of cohort 1 versus cohort 2 there was no statistical significance in median age, white blood count, absolute neutrophil count, platelets, peripheral blood and bone marrow blasts, bone marrow cellularity and sex. Median number of cycles was expectedly higher in cohort 2 vs 1 (9 vs 2, p<0.0001). Intermediate cytogenetic risk was more common in cohort 2 vs 1 (90% vs 43%, p=0.006), while poor risk was more common in cohort 1 vs 2 (57% vs 10%, p=0.006). Only 10% had complex karyotype in cohort 2 compared to 50% in cohort 1 (p=0.017). NPM1 mutation was absent in all cases, while FLT3 mutation was present 30% in cohort 1 and 25% in cohort 2 (p = 0.9). Decitabine was more commonly given in cohort 1 vs cohort 2 (80% vs 50%, p =0.07). iii) Clinical outcome of HMA SD cohorts : Median overall survival was higher in long-lasting SD patients (cohort 2) vs short-lasting SD (18 vs 4 months, p = 0.0002). Upon multivariate analysis, both age (p <0.0001) and long-lasting SD (p =0.01) were statistically significant for overall survival but not cytogenetics risk grouping nor type of HMA administered. Conclusions: Standard response criteria for AML by IWG were developed for intensive chemotherapy and do not apply to newer agents, specifically HMA. Stable disease (SD) could be meaningful to some elderly AML patients when treated with HMA. Intermediate cytogenetics and azacitidine use were more frequent in patients with long-lasting SD. Long-lasting SD did confer a survival benefit in elderly AML patients. Newer response criteria for assessing novel agents' efficacy are needed in this population. Figure Figure. Disclosures Tibes: Italfarmaco S.p.A.: Consultancy, Honoraria. Foran:pfizer: Honoraria; Millennium Pharmaceuticals, Inc.: Research Funding; medscape: Honoraria; karyopharm: Honoraria; novartis: Honoraria; boehringer ingelheim: Research Funding; agios: Research Funding; Cellerant: Research Funding. Al-Kali:Novartis: Research Funding; Celgene: Research Funding.

Abstract Abstract 3554 Introduction: The role of SCT in the management of Ig light chain (AL) amyloidosis remains undefined. Patients: We report 422 patients (Table 1) who received SCT for AL amyloidosis to compare outcomes of patients treated before January 2006 with those of patients treated from January 2006 until December 1, 2009. Results: Day 100 all-cause mortality decreased over this time period from 12% to 7% (P=.09) figure 1. Survival at 2 years increased from 78% to 82%. Figure 2 The major determinants of early mortality (before day 100) were the presence of cardiac involvement with amyloid and increased levels of cardiac biomarkers, lower serum albumin, higher serum creatinine, and a higher number of organs involved. (Table 2) On multivariate survival analysis, higher levels of serum troponin T and N-terminal pro–brain natriuretic peptide were the only predictors of early mortality after SCT. Conclusion: Improved supportive care and refined patient selection has improved the safety margin for patients undergoing SCT; short-term mortality showed a more than 40% decrease after 2005. Recognition of this decrease in mortality is important for physicians caring for these patients as they weigh the pros and cons of SCT vs novel agent-based treatment in management of amyloidosis. 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 Background: AML outcome in elderly patients unfit for intensive chemotherapy continues to be challenging. Hypomethylating agents (HMA) can be effective in these patients but responses are short-lived (Fenaux et al, JCO 2009; Dombret et al Blood 2015). Even though HMAs achieve superior response rates to supportive care alone, complete remissions (CR) are rarely achieved and often quickly lost when they occur. The majority of patients will either have stable disease or progress through therapy. We hereby describe the outcome of these patients at our institution after they fail HMAs. Methods: A total of 56 AML patients' data from Feb 2007 to June 2015 at Mayo Clinic were reviewed after appropriate IRB approval was obtained. All cases had their bone marrow slides reviewed at our institution. Patients were considered for our study if they received HMA as frontline therapy for their AML. Patients who received HMAs after induction chemotherapy failure or for their MDS were excluded. Response was identified based on IWG AML criteria (Cheson et al, JCO 2003). Prognostic factors were analyzed by univariate and multivariate analyses. Survival estimates were calculated using Kaplan-Meier curves and univariate and multivariate analyses was based on log-rank testing using JMP software version 10. Results: i) Characteristics at Diagnosis: We identified 56 AML patients treated with HMA as frontline therapy with median age of 76 years (range, 59-91), 68% of which were males. Cases were classified as AML with myelodysplasia related changes in 25%, and therapy related myeloid neoplasm in 2%, and not otherwise specific in 73%. Out of 56 cases, 23% were secondary to MDS, 2% ET (Essential Thrombocytopenia), 5% PV (Polycythemia Vera), 5% MF (Myelofibrosis), 4% from CMML (Chronic Myelomonocytic Leukemia); while 61% were de novo AML. Per cytogenetics data, 2% were considered favorable risk, 62% intermediate, and 36% poor (34% had complex karyotype). ii) Clinical outcome to Frontline HMA: Out of 56 patients, 15(27%) patients received azacitidine (AZA) and 41 (73%) received decitabine (DAC) with a median number of cycles of 4 (range 1-62). Median number of cycles was higher for AZA vs DAC (8 vs 4, p =0.3). CR was found in 10 (18%), CR with incomplete count recovery in 3 (5%), partial remission (PR) in 3 (5%) patients, with overall response of 28% and median response duration of 10 months (range, 1-78 months). Thirteen (81%) out of 16 responders relapsed. Therefore, only 53 patients were included in primary or secondary failure analysis. iii) Clinical outcome to Frontline HMA failure: Out of 53 patients, 12 (23%) received subsequent treatments. Out of the 12 patients, 3 (25%) received another HMA (switch), 2 (17%) subcutaneous low dose cytarabine, 4 (33%) intensive chemotherapy, while 3 (25%) received either therapy on a clinical trial or targeted therapy. None of the 12 patients who got first salvage therapy achieved remission. Five out of the 12 patients received second salvage therapy, 2 (40%) of which achieved CR. Only one patient had third salvage therapy and did not respond. No patient was able to proceed to allogenic hematopoietic cell transplantation. Median overall survival (mOS) for this group was 2 months. Median OS for patients who received subsequent salvage therapies was better than those who did not receive any subsequent therapy after failing HMA (9.5 vs 2 months, p = 0.0009). Conclusions: Elderly patients diagnosed with AML who are unfit for intensive chemotherapy have a poor prognosis. HMA can get some patients into remission but most patients will ultimately fail. Outcome for patients who have primary or secondary (relapse) failure is very poor with a median OS of 2 months. Switch of HMA did not result in any response. Response to salvage therapy continues to be low but offering salvage therapies seem to improve OS. Our study provides historical data for future novel therapies, which are sorely needed for these patients. Figure Figure. Disclosures Al-Kali: Celgene: Research Funding; Onconova Therapeutics, Inc.: Research Funding.

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 Background: In a previously published phase-1/2 study, momelotinib (a JAK 1/2 inhibitor) induced 53% anemia, 39% spleen and >50% constitutional symptoms response rates in patients with myelofibrosis (MF) (Pardanani A, et al. Leukemia. 2013;27:1322). The particular study included 100 patients from the Mayo Clinic who experienced 43% spleen and 44% anemia response rates (Pardanani et al. Leukemia. 2015;29:741); CALR and ASXL1 mutations independently predicted spleen but not anemia response. In the current study, we examined the impact of momelotinib therapy on DIPSS-plus- and molecular risk-adjusted survival. Methods: The current study represents sponsor-independent analysis of long-term survival among 100 consecutive Mayo Clinic patients who received momelotinib therapy as part of a larger (n =166) phase-1/2 study (NCT00935987). Safety and efficacy data from NCT00935987, as well as protocol design and drug dosing and schedule, have already been formally reported and not reiterated here (Pardanani A, et al. Leukemia. 2013;27:1322; Pardanani A, et al. Leukemia. 2015;29:741; Abdelrahman RA, et al. BJH. 2015;169:77). All statistical analyses considered clinical and laboratory parameters obtained at the time of entry to study. Survival analysis was considered from the date of study entry to date of death or last contact. Cox proportional hazard regression model was used for multivariable analysis of survival. Samples from time of study entry were used for mutation screening. Driver mutations were classified into two prognostically-relevant groups: CALR type 1/type 1-like (favorable) vs all others including CALR type 2/type 2-like, JAK2, MPL and triple-negative (unfavorable). Results: 100 patients with MF (median age 66 years; 58% males) were treated at the Mayo Clinic between 11/20/09 and 11/10/10; 64 patients had primary MF, 22 post-polycythemia vera MF and 14 post-essential thrombocythemia MF. Baseline data: DIPSS-plus risk distribution was 63% high, 36% intermediate-2 and 1% intermediate-1 (JCO 2011;29:392); for the purposes of the current analysis, the single patient with intermediate-1 risk disease was included in the intermediate-2 category. 54 (54%) patients displayed abnormal karyotype. 73 (73%) patients harbored JAK2, 16 (16%) CALR, 7 MPL and 4 "triple-negative". Among the 16 CALR -mutated cases, 13 were classified as "type 1/type 1-like". 94 patients were screened for ASXL1 mutations; 41 (44%) were mutated. Follow-up data was updated in July 2015, providing a minimum follow-up of over 4.5 years since the last patient registration on the protocol. At a median follow-up of 3.2 years, 67 (67%) deaths and 13 (13%) leukemic transformations were documented. Median survival from the time of study entry was 3.2 years and was affected by driver mutation prognostic groups (median survival "not reached" for "favorable" vs 3 years for "unfavorable"; p=0.01), ASXL1 mutational status (median survival 3.9 years in unmutated vs 2.5 years in mutated; p=0.02) and DIPSS-plus risk stratification (median survival 2.6 years in high-risk vs 4 years in intermediate-2 risk; p=0.07). In order to assess the impact of momelotinib on long-term outcome, we compared survival of the study cohort (n =100) with that of 442 consecutive Mayo Clinic patients with high or intermediate-2 risk primary MF (median age 67 years; 66% males). There was no significant difference between this control group of PMF patients versus the momelotinib patient cohort in distribution of age (p=0.56), sex (p=0.12), JAK2/CALR/MPL mutational status (p=0.41) or ASXL1 mutational status (p=0.9); however, the momelotinib cohort had a higher fraction of patients with DIPSS-plus high-risk disease (63% vs 47%; p=0.004). Overall survival was similar between the momelotinib cohort and the control group of PMF patients who were not treated with momelotinib (Figure 1; p=0.99); the difference in survival remained not significant during multivariable analysis that included risk stratification by DIPSS-plus (p=0.32), "favorable" vs "unfavorable" driver mutational status (p=0.78) or ASXL1 mutational status (Figure 2; p=0.61). Conclusions: In the current long-term study, we could not demonstrate a survival impact from momelotinib therapy in myelofibrosis. Although adjusted for clinical and molecular risk status, our study is retrospective and cannot be relied upon to discount marginal survival effect. Disclosures Al-Kali: Novartis: Research Funding. Pardanani:Stemline: 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 Abstract 4109 Background: In a previous study, we reported safety and efficacy of low-dose (0.5 mg/d) pomalidomide and prednisone and pomalidomide alone (2 mg/d) for the treatment of anemia associated with myelofibrosis (J Clin Oncol 2009; 27: 4563). The current study examined the value of low dose pomalidomide alone (ClinicalTrials.gov No. NCT00669578). Methods: Persons with primary (PMF) or post-polycythemia vera/essential thrombocythemia (post-PV/ET MF) myelofibrosis were studied. The main eligibility criterion was RBC-transfusion-dependence or hemoglobin <10 g/dL. Subjects failing lenalidomide or thalidomide were eligible whereas those with deep vein thrombosis or pulmonary-embolism <1 y pre-study entry were not. The primary endpoint was anemia response assessed by the International Working Group for Myeloproliferative Neoplasms Research and Treatment criteria (Blood 2006; 108: 1497). Results: Pomalidomide (0.5 mg/d) was given to 58 subjects (median age 68 y; 44 males). 46 (79%) were RBC-transfusion-dependent and 42, JAK2V617F-positive. Baseline disease-stage at time of study-entry according to the Dynamic International Prognostic Scoring System (DIPSS; Blood 2010; 115: 1703) was high-risk in 16 (28%) and intermediate-2 risk in 42 (72%). Cytogenetic findings were favorable in 46, unfavorable in 9 and not evaluable in 3. 46 (79%) had PMF and the remainder post-PV/ET MF. 49 (84%) patients completed ≥3 mo of therapy. Treatment was well-tolerated with no instances of thrombosis. There was grade-1 neuropathy possibly related to drug in 1 subject. ≥Grade-3 thrombocytopenia/neutropenia occurred in 2 subjects. There was an anemia response in 10 (17%) subjects including 9 who became RBC-transfusion-independent. Median response-duration was 8+ mo (range, 6–13 mo). 14 of 24 subjecst (58%) with platelets ≤100 × 10e9/L had a >50% increment. There were no spleen responses. Anemia response occurred only in subjects with JAK2V617F (24% vs. 0; p=0.03) but was not correlated with mutant allele burden (p=0.39). Anemia response in JAK2V617F-positive subjects was predicted by the presence of pomalidomide-induced basophilia in the 1st month of therapy (38% vs. 6%; p=0.02) or absence of marked splenomegaly (38% vs. 11%; p=0.05); response was not affected by cytogenetic risk-category (p=0.96) or WBC (p=0.27). Conclusions: These data suggest that low-dose pomalidomide is effective in the treatment for anemia associated with JAK2V617F-positive myelofibrosis, especially in the absence of marked splenomegaly. Response appears to be predicted by early drug-induced basophilia. Pomalidomide also appears to improve thrombocytopenia in most subjects with baseline platelets <100 × 10e9/L but is not active in controlling disease-associated splenomegaly. Disclosures: Mesa: SBio: Research Funding; Novartis: Research Funding; Celgene: Research Funding; Incyte: Research Funding; Roche: Research Funding; eisai: Research Funding; telik: Research Funding.