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Abstract Abstract 3838 Background: SAR302503 (SAR503, formerly TG101348), a potent, oral JAK2-selective inhibitor was studied in a Phase I/II trial for the treatment of patients with high- or intermediate-risk primary, post-polycythemia vera (PV) and post-essential thrombocythemia (ET) myelofibrosis (MF). SAR503 was administered orally once daily in 28-day cycles. Eligibility criteria included platelet count of ≥50 × 109/L. Interim safety and efficacy data from this study up to April 2010 have been previously published (JCO 2011, 29(7):789–796). The aim of this presentation is to report updated safety and efficacy of ongoing patients as well as an analysis of the JAK2V617F allele burden in this cohort. Results: Overall, 59 subjects (median age 64 years) were treated. Forty four patients had PMF, 12 post-PV MF and 3 post-ET MF; 86% were JAK2 V617F-positive. Median palpable spleen size was 18 cm at study enrollment. Twenty eight patients were treated in the dose-escalation cohort (30–800 mg administered as a single daily dose); thirty one patients were treated at the MTD (680 mg) in the dose confirmation cohort. 43/59 patients (73%) completed 6 cycles of treatment and continued treatment on the extension study. Currently, 22 patients (37%) remain on treatment with a median number of 28.5 cycles (24–41 range) and a median of last dose of 440 mg/day. Safety: Treatment-emergent toxicities in cycle 1–6 have been previously reported; toxicities were dose-dependent and generally alleviated with dose-reduction. Five patients discontinued treatment beyond cycle 6 for treatment-related adverse events: thrombocytopenia, depression, mental status changes, creatinine elevation and subdural hematoma. For the subgroup of patients with a baseline platelet count between 50–100 × 109/L (n =13; median 73, range 51–94); the platelet count at defined times points during follow up was: cycle 3; median 50, range 21–138 (p=0.09) and cycle 6; median 47, range 13–85 (p=0.01). Despite 7 of the 13 patients being treated at ≥680 mg/day, only 2 instances of Grade 4 thrombocytopenia were noted in this group Spleen response: As previously reported, spleen responses were seen early, usually within first 3 cycles, with half or more patients in each dose level ≥240 mg/day showing a durable ≥50% decrease in palpable spleen size. Spleen size (mean, median, range, and proportion with ≥50% reduction) at the following time points was: Baseline (n=58; 18.33cm, 18cm, 4–38cm, NA) ; 6 months (n=57; 9.05cm, 9cm, 0–30cm, 54.4%;) 12 months (n=42; 8.55cm, 9cm, 0–28cm, 66.7%) 18 months (n=36; 8.03cm, 8.5cm, 0–33cm, 52.8%); 24 months (n=31; 8.10cm, 8cm, 0–30cm, 54.8%,) 30 months (n=18; 6cm, 7.5cm, 0–16cm, 61.1%,and) 36 months (n=9; 5.89cm, 3cm, 0–16cm, 66.7%). JAK2V617F allele burden: We previously reported a significant decrease in JAK2V617F allele burden at the end of cycles 6 and 12. A durable decrease was also demonstrable after 24 cycles of treatment (n =21; median 9%, range 0–100%) relative to baseline (n =51; median 20%, range 3–100%) (p=0.03). Similarly, for patients with JAK2 V617F allele burden >20% at baseline; there was a significant decrease after cycle 24 (n =12; median 21%, range 6–100%) relative to baseline (n =23; median 60%, range 23–100%) (p=0.03). Conclusions: SAR503 is safe and efficacious treatment with long term effect on spleen size and JAK2V617F allele burden in patients with high- and intermediate-risk myelofibrosis. Additional follow up information will be updated at the time of meeting. Disclosures: Jamieson: Wintherix: Equity Ownership; Pfizer Oncology: Research Funding; Celgene: Research Funding; Novartis: Honoraria. Gao:Sanofi-Aventis: Employment. Zhang:Sanofi-Aventis: Employment. Neumann:Sanofi-Aventis: Employment.

Abstract Relatively little is known about the quality of life (QOL) status among long-term (5–20 year) lymphoma survivors. Using the Mayo Tumor Registry, we identified eligible patients who were 16 years or older at diagnosis, U.S. residents, first diagnosed with Hodgkin or non-Hodgkin lymphoma from 1984–1998, diagnosed and/or initially treated at Mayo Clinic Rochester, and survived for 5 to 20 years (N=2,485). In October of 2004, we mailed a 23-page survey to 95 randomly selected patients; 7 were found to be ineligible (deceased or too ill). Of the 88 remaining patients, we were able to find a correct address for 82, and 57 completed a survey for a 70% participation rate. QOL assessments included the Functional Assessment of Cancer Therapy - General (FACT-G), and a series of linear analogue self-assessment (LASA) single-item QOL measures. Results for the pilot sample were compared to normative data for each measure relating to general cancer patient populations. All scores were transformed onto a 0–100 point scale (higher score meaning higher functioning) for ease of comparison. Of the 54 patients with complete data for analysis, the mean age at survey was 60.8 years (6.3–19.9). The mean time since diagnosis was 12.0 years (6.3–19.9), and 52% had survived more than 11 years. The mean total score for the FACT-G was 89 compared to a norm of 74 for cancer patients. Higher scores were also seen in the lymphoma survivors in each of the four FACT-G subdomains (physical, social/family, emotional and functional well-being) compared to normative cancer patient populations. The global LASA QOL measure was also higher among lymphoma survivors (mean score of 82 compared to a norm of 77), and only 7% reported a global QOL score of 50 or lower, indicative of impaired QOL. Functioning among the lymphoma survivors was higher compared to general cancer patients on the mental, physical, emotional, social, pain, fatigue, financial, and legal LASA items, while functioning was similar to general cancer patients on the spiritual and support LASA items. However, scores suggestive of impaired QOL were reported by more than 10% of the patients for the social (17%), pain frequency (31%), fatigue (20%), and financial concerns (25%) items of the LASA. There were suggestive results of effect sizes indicating that smokers had lower FACT-G physical and emotional scores, and lower LASA mental and physical QOL scores, although none achieved statistical significance. In conclusion, this pilot sample of long-term lymphoma survivor patients reported having high QOL on most domains of the FACT-G and LASA relative to other cancer patient populations. There appears to be a subset of patients who experience impaired QOL and who may require further interventions, particularly in the QOL domains of social, pain, fatigue, and financial functioning. These results also suggest that awareness of smoking status may be important. Further larger studies are needed to confirm these preliminary data and to evaluate other aspects of QOL.

Abstract Abstract 1752 Background: Patients with primary (PMF) or post-polycythemia vera/essential thrombocythemia (post-PV/ET MF) myelofibrosis often harbor a JAK2 mutation and also display abnormally increased inflammatory cytokines (J Clin Oncol. 2011;29:1356). Therefore, JAK-STAT is an appealing drug target in such patients. Ruxolitinib (INCB018424) is a small molecule ATP mimetic that inhibits both JAK1 and JAK2 and has been evaluated for its therapeutic activity in MF, in the setting of phases 1, 2, and 3 clinical trials. Methods: The first phase-1/2 MF study using ruxolitinib was conducted at the MD Anderson Cancer Center and Mayo Clinic. A total of 153 patients were included in the study whose first line results were published in September, 2010 (NEJM 2010;363:1117). The current report constitutes a sponsor-independent analysis of long-term outcome in the 51 Mayo Clinic patients who participated in the particular clinical trial. Results I: Baseline characteristics: The 51 patients (37 males) from the Mayo Clinic were enrolled between October, 2007 and February 2009. The median time from treatment initiation is now 3.5 years. MF subtype distributions were PMF 60%, post-PV MF 32% and post-ET MF 10%. Median (range) values were age 61 years (39–79), hemoglobin 10.6 g/dL (7.4-15.3), leukocyte count 15.8 (2.0–136), and palpable spleen size 19 cm (0–32). The proportion of patients with red cell transfusion dependency was 24%, hemoglobin <10 g/dL 38%, unfavorable karyotype 18%, pruritus 24%, night sweats 26%, and JAK2V617F 84%. DIPSS-plus risk distributions were high 18%, intermediate-2 48%, intermediate-1 22% and low 14%. Results II: Response and treatment duration: According to the International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria, spleen response rate was 29% and anemia response rate 21%. Responses were also seen in constitutional symptoms (63%) and pruritus (92%). To date, treatment has been discontinued in 47 (92%) patients. The treatment discontinuation rates at 1, 2 and 3 years were 51%, 72% and 89%, respectively. For the 47 patients who were taken off study, median duration of treatment was 9.2 months (range 1.3–42 months). Reasons for treatment discontinuation included loss or lack of response/disease progression (∼40%), toxicity with and without lack of response/disease progression (∼34%), patient/physician choice often associated with lack of response (13%), and death on study (∼4%). Results III: Toxicity: Grade ≥2 thrombocytopenia and anemia occurred in 26% and 33% of patients and persisted in the majority of afflicted patients after drug discontinuation. To date, 18 deaths (36%) and 5 (10%) leukemic transformations have been recorded. Serious adverse events occurred upon drug discontinuation in 6 cases (13%) and were characterized by immediate relapse of symptoms, rapid and painful enlargement of spleen sometimes associated to splenic infarct, and acute hemodynamic decompensation occasionally leading to a septic shock-like syndrome. Results IV: Survival: There was no significant difference in the survival of the 51 ruxolitinib-treated patients compared to that of a cohort of 410 cases of PMF seen at the Mayo Clinic in the most recent 10-year period: unadjusted (Figure 1; p=0.43) and adjusted for DIPSS-plus (Figure 2; p=0.58). Conclusions: Ruxolitinib is effective in alleviating constitutional symptoms in the majority of patients with MF. Its activity in reducing spleen size is modest and not always durable. It is imperative that patients be alerted about important drug adverse events including potentially irreversible thrombocytopenia, worsening of anemia, and potentially catastrophic withdrawal symptoms. Ruxolitinib therapy does not appear to affect survival in MF. Disclosures: No relevant conflicts of interest to declare.

Abstract Patients during cancer treatment and cancer survivors frequently utilize complementary and alternative medicine (CAM) therapies. While the beliefs and knowledge regarding CAM of many cancer-specific patient groups have been well studied such as breast cancer patients and prostate cancer patients, no specific evaluation of lymphoma survivors and their beliefs and knowledge about CAM has been undertaken. Because CAM can yield both risks such as toxicity and displacement of efficacious therapy as well as potential benefits such as improvement in quality of life and mood, we surveyed lymphoma survivors in a pilot study to ascertain their current beliefs, knowledge, and utilization of CAM. Using the Mayo Tumor Registry, we identified eligible patients who were 16 years or older at diagnosis, U.S. residents, first diagnosed with Hodgkin or non-Hodgkin lymphoma from 1984–1998, diagnosed and/or initially treated at Mayo Clinic Rochester, and survived for 5 to 20 years (N=2,485). In October of 2004, we mailed a 23-page survey to 95 randomly selected patients; 7 were found to be ineligible (deceased or too ill). Of the 88 remaining patients, we were able to find a correct address for 82, and 57 completed a survey for a 70% participation rate. Complete data were available on 54 patients at the time of this analysis. The mean age at completion of the questionnaire was 60.8 years (26.1–86.7). The mean time since diagnosis was 12.0 years (6.3–19.9), and 52% survived more than 11 years. The histologies included 22 (39%) Hodgkin lymphoma, 21 (38%) diffuse large B-cell, 3 (5%) follicular, 1 (1%) high grade, 5 (9%) peripheral T-cell lymphoma, and 4 (7%) other. A majority of patients expressed no knowledge about the use of CAM cancer care, while only 4% of patients responded that CAM could both cure cancer and that it was perfectly safe. Ten to twenty percent of patients felt that CAM could assist other therapeutic interventions, relieve symptoms, assist the body to heal or increase quality of life. Fifteen percent of patients reported that CAM utilization increased the feeling of control, and 24% reported that CAM could have side effects. With respect to CAM utilization, overall 32% of patients had ever used CAM, but no patients reported that CAM usage was directed specifically towards their lymphoma. The most commonly used CAM modalities were chiropractic (39%), massage (21%), relaxation therapy (7%), meditation (5%) and acupuncture (5%). Overall usage of dietary supplements was relatively low, with green tea, garlic, flax seed, and echinacea being the only dietary supplements used by more than 10% of respondents. Five percent had used St. John’s Wort and 7% had used shark cartilage. In conclusion, lymphoma long-term survivors appear to use CAM at a rate similar to the general population, which does not follow the typical pattern seen in other cancer survivorship populations. The use of St. John’s Wort has potential risks if not identified prospectively. At the same time, lack of access to potentially beneficial modalities was also identified, and these observations suggest the opportunity for further study of targeted educational interventions regarding the use of CAM in this population.

Abstract Background: Using fluorescent in-situ hybridization (FISH), a number of investigators have identified specific cytogenetic abnormalities that identify CLL patients with a more aggressive (17p-, 11q-) or indolent (13q-) disease course. Some have suggested patients who initially have a normal karyotype may acquire new chromosome abnormalities during the course of their disease. Since patients with specific cytogenetic abnormalities (17p-, 11q-) are less likely to respond to purine nucleoside analogues, such clonal evolution has potential implications for treatment as well as prognosis. No study has prospectively investigated the frequency of clonal evolution in a cohort of patients with newly diagnosed untreated CLL. Methods: Between 1994 and 2000, we enrolled 167 patients with previously untreated CLL seen at Mayo Clinic in a prospective trial evaluating the prognostic importance of cytogenetic abnormalities and clonal evolution detected by FISH. All patients provided a baseline blood specimen for FISH testing and follow-up specimens over the following 24 months. Other research samples from later timepoints were tested where available. Study participants were contacted by mail in 2004 to update vital and treatment status. Of 83 living responders, 70 (84%) indicated they would be willing to provide an additional follow-up sample for cytogenetic analysis of whom 48 have returned a sample to date. Results of clinical FISH testing during the follow-up interval were also abstracted. FISH was performed on interphase nuclei from blood as we have previously described (BJH 121:287). Results: Median age at diagnosis was 64. Median time from diagnosis to study enrollment was 3.3 months. 94% of patients had early stage disease at enrollment (88 Rai 0; 48 Rai I, 18 Rai II, 2 Rai III; 8 Rai IV). Median follow-up time from diagnosis for all 164 eligible study participants was 8.5 years (range: 0.33–22.9 yrs). As of last follow-up, 48% of patients have received treatment and 57 (35%) have died. 75% of patients had chromosome abnormalities on FISH testing at baseline. The frequency of individual cytogenetic abnormalities on baseline FISH analysis along with overall survival by hierarchical FISH risk category are shown in Table I. 106 patients had sequential samples for FISH analysis at least 2 years apart, 61 had samples at least 5 years apart, and 22 had samples at least 10 years apart. 15 patients had evidence of clonal evolution during follow up as evidenced by a new FISH anomaly not present on the baseline specimen. No clonal evolution was observed in the first 2 years of follow-up (n=106), however of 61 patients with samples at least 5 years apart, 14 (23%) had evidence of clonal evolution. Median time for development of a new cytogenetic abnormality among these patients was 9.3 years. Conclusions: Clonal evolution occurs during the course of disease for approximately 25% of patients with early stage CLL. Clonal evolution appears to occur at low frequency during the first 2 years of follow-up but increases in frequency after 5 years. This finding has potentially significant implications for prognosis and treatment of patients with CLL. FISH Risk Category* N (Baseline) Median Overall Survival (Years) * Difference between groups significant p=0.0038 13q- x 1 37 14.4 13q- x2 35 17 Normal Karyotype 40 13.2 12+ 24 11.1 11q- 12 8.6 17p- 10 10.5 6q- 2 4.1 Other 2 Not reached

Abstract It has been well-documented in cardiac patients and in the general population that physical activity improves physical and mental health. Physical activity could also improve the health and quality of life of long-term lymphoma survivors, but little is known about physical activity in this group of patients. Using the Mayo Tumor Registry, we identified eligible patients who were 16 years or older at diagnosis, U.S. residents, first diagnosed with Hodgkin or non-Hodgkin lymphoma from 1984–1998, diagnosed and/or initially treated at Mayo Clinic Rochester, and survived for 5 to 20 years (N=2,485). In October of 2004, we mailed a 23-page survey to 95 randomly selected patients; 7 were found to be ineligible (deceased or too ill). Of the 88 remaining patients, we were able to find a correct address for 82, and 57 completed a survey for a 70% participation rate. Physical activity was self-reported using the Godin (1985) Leisure-Time Exercise Questionnaire. Of the 54 patients with complete data for this report, the mean age at completion of the questionnaire was 60.8 years (26.1–86.7). The mean time since diagnosis was 12.0 years (6.3–19.9), and 52% survived more than 11 years. The histologies included 22 (39%) Hodgkin lymphoma, 21 (38%) diffuse large B-cell lymphoma, 3 (5%) follicular lymphomas, 1 (2%) high-grade lymphoma, 5 (9%) peripheral T-cell lymphomas, and 4 (7%) other. Regular fitness was reported by 21% of the respondents. This is lower than a recent report of adults aged 50 years and older, where approximately 40% of those free of chronic disability were attaining recommended daily physical activity levels. It is also lower than the expected 30% in patients with disabilities from the Behavioral Risk Factor Survey (Brown DR et al., Med Sci Sports Exerc2005;37:620–9). In addition, although not statistically significant, there were effect sizes observed suggesting that sedentary responders had higher levels of depression, higher anxiety levels, more distress, and lower quality of life (QOL) compared to physically active respondents. These finding need to be verified in a larger sample to obtain better estimates. In conclusion, levels of physical activity were lower than general population samples. These results also suggest that physical activity level may be related to improved mood and QOL in this population.

Abstract Abstract 2105 The existence of multiple inherited disorders of iron metabolism in man, rodents and other vertebrates suggests genetic contributions to iron deficiency. We hypothesized that common variants in genes involved in iron metabolism may modulate susceptibility or resistance to the development of iron deficiency in humans. To examine the association between single nucleotide polymorphisms (SNPs) in key genes involved in iron metabolism pathways, we previously performed a genome-wide association study using DNA collected from white men aged ≥25 y and women ≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) ≤12 μg/L (cases) and controls (SF >100 μg/L in men, SF >50 μg/L in women). We now report on a multiethnic follow-up association study of HEIRS participants. Candidate SNPs were identified from our GWAS and the scientific literature. Population samples of whites, African Americans, Hispanics, and Asians from the U.S. and Canada were analyzed separately for association between SNPs and case-control status and each of seven quantitative outcomes including serum iron, total iron-binding capacity (TIBC), unsaturated iron-binding capacity (UIBC), transferrin saturation, SF, serum transferrin receptor, and body iron. There were 1084 white (357 cases, 727 controls), 153 Asian (51 cases, 102 controls), 221 African American (77 cases, 144 controls) and 233 of 239 Hispanic individuals (79 cases, 160 controls) that passed quality control. For the African-American and Hispanic samples, ancestry proportions were estimated based on genotypes of ancestry informative markers. Regression analysis was used to examine the association between case-control status and quantitative serum iron measures and 1134, 1115, 1113 and 1134 SNP genotypes in the white, African-American, Hispanic, and Asian population samples, respectively. Model predictors included age, sex, the estimated ancestry proportion (for African American and Hispanic only), genotype, and measured covariates that showed nominally significant associations with the outcome. Three chromosomal regions showed evidence of association across multiple populations, including SNPs in the TF gene on chromosome 3q22, the TMPRSS6 gene on chromosome 22q12, and loci on chromosome 18q21. SNP rs1421312 in TMPRSS6 was associated with serum iron in whites (p=4.7×10−7) and was replicated in African Americans (p=0.0012).Twenty SNPs in the TF gene region were significantly associated with TIBC in the white sample (p<4.4×10−5); six SNPs were replicated in other ethnicities (p< 0.01). SNP rs10904850 in the CUBN gene on 10p13 was significantly associated with serum iron in the African-American sample (P=1.0×10−5). Mutations in the TMPRSS6 gene have been implicated in iron-refractory iron deficiency anemia through linkage studies. We found a novel SNP in TMPRSS6 that was associated with serum iron in whites and replicated in African Americans, suggesting a role for this SNP in increasing the risk of iron deficiency in affected persons. Our results confirm known associations with iron measures and give evidence of their role in different ethnic groups, a unique aspect of this study, suggesting origins in a common founder. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 4094 Background: Our group has previously reported the benefits of thalidomide-prednisone based regimens for improvement of anemia, thrombocytopenia, and splenomegaly for patients with MF; both primary myelofibrosis (PMF), and arising from essential thrombocythemia and polycythemia (Post ET/PV MF). We sought to evaluate the overall efficacy of these commonly used regimens by evaluating long-term outcomes and applying the IWG-MRT response criteria (Tefferi et. al. Blood 2006) which arose after completion of these trials. Methods: We retrospectively analyzed the long-term outcomes, and assessed the initial therapeutic responses using IWG-MRT criteria from three parallel completed trials of MF using a thalidomide (THAL-50 mg/day) and prednisone (3 month taper beginning at 40mg, stopped at 3 months) backbone. The trials had identical eligibility criteria including adequate organ function and need for MF therapy (defined as symptomatic: anemia and/or splenomegaly). The trials were 1) THAL-PRED alone, THAL only after 3 months 2) THAL-PRED-etanercept (ETAN - TNF- alpha inhibitor at 25 micrograms subcutaneously twice a week), THAL and ETAN only after 3 months and 3) THAL-PRED – oral cyclophosphamide (CTX 25mg daily orally), THAL alone after 3 months. Results: Patients: A total of 50 pts were enrolled in these 3 trials (Males n=36, 72%) with median age of 68.5 years (Range 43–85), with 79% having PMF. Patients had advanced disease in general with 88% having intermediate 2 or high risk MF by IWG criteria (Cervantes et. al. Blood 2009), 62% patients with red cell transfusion dependence and 50% with an abnormal karyotype. Therapy initial results: 80 % of patients reached the three month juncture on the trials, with 40% reaching 6 months. Initial toxicity was myelosuppression with 3 cases of grade 3 anemia, 3 cases of grade 3 neutropenia and 4 cases of grade 3 thrombocytopenia. There were no grade 4 or higher hematological toxicities noted. Initial neuropathy was uncommon and seen in only 4% of patients. No complete responses were observed and only 1 patient had partial response (by IWG-MRT criteria). 14 patients (28% overall) met the new IWG-MRT criteria for clinical improvement; 11 for anemia (22%), 2 for thrombocytopenia (4%) and 3 for splenomegaly (6%). Responses occurred relatively quickly at an overall median of 8 weeks (range 4–12) after enrollment. Long Term Outcomes: After a median follow-up of 36 months across this cohort we observed an overall median duration of response of 8.5 months (range 3–42). Responses to THAL based regimens can lead to periods of prolonged stabilization after cessation of therapy. We observed an overall median time to institution of next therapy of 3 months (range 1–50). At the time of this analysis 14 patients (28%) have expired of their MF and median survival across the entire cohort was 36 months (3-106). Comparison of Regimens: Comparison of these three independent trials (Table 1) suggests greater toxicity and inferior response rate, duration of response, and time to next therapy with the cyclophosphamide containing regimen. Conclusion: THAL-PRED based regimens are active in a subset of MF patients for therapy primarily of anemia, and for some patients a response of good duration (even after cessation of therapy) may be obtained. IWG-MRT response assessment demonstrates utilizing additional agents to a THAL-PRED regimen do not appear to augment (and may detract from responses). Newer agents such as pomalidomide may have similar to greater efficacy without neuropathy and less myelosuppression. Disclosures: Off Label Use: There is no FDA approved agent in Myelofibrosis. All the drugs discussed; Thalidomide, Prednisone, Etanarcept and Cyclophosphamide are off-label. Mesa:SBio: Research Funding; Novartis: Research Funding; Celgene: Research Funding; Incyte: Research Funding; Roche: Research Funding; eisai: Research Funding; telik: Research Funding.

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 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.