ALBERT

Description: Abstract 1753 Background: Ruxolitinib (INC424), a potent and selective oral JAK1 and JAK2 inhibitor, has demonstrated rapid and durable reductions in splenomegaly and improved disease-related symptoms, role functioning, and quality of life (QoL) in 2 phase 3 studies in patients with myelofibrosis (MF) (the COMFORT studies). These studies compared ruxolitinib with either placebo or best available therapy (BAT). This analysis compares the efficacy outcomes between the placebo arm from COMFORT-I and the BAT arm from COMFORT-II. Methods: COMFORT-I is a randomized (1:1), double-blind, multicenter study comparing ruxolitinib 15 or 20 mg twice daily (bid) with placebo, and COMFORT-II is a randomized (2:1), open-label, multicenter study comparing ruxolitinib 15 or 20 mg bid with BAT (investigator-selected therapy, including no treatment). Both studies met their primary end points with statistical significance (ruxolitinib vs control): the percentage of patients achieving ≥35% reduction in spleen volume at week 24 (COMFORT-I, P

Description: Abstract 795FN2 Background: Ruxolitinib (INC424), a potent and selective oral JAK1 and JAK2 inhibitor, demonstrated rapid and durable reductions in splenomegaly and improved disease-related symptoms, role functioning, and quality of life (QoL) in 2 phase 3 studies in patients with myelofibrosis (MF) (the COMFORT studies). Per-protocol, patient-reported, health-related QoL (HRQoL) and symptoms analyses in the COMFORT-II study are limited. Here we report on additional post hoc analyses of these outcomes. The COMFORT-II study includes 219 patients (ruxolitinib, n=146; best available therapy [BAT], n=73). At entry, all patients were classified into intermediate 2-risk or high-risk prognostic groups (Cervantes F, et al. Blood, 2009;113(13):2895-2901) and had palpable splenomegaly ≥5 cm below the costal margin. Patients could have received prior therapy for MF. On BAT, doses and schedules or no therapy were selected by the investigator; therapy adjustments were permitted during the randomized treatment phase at the investigator's discretion. Patients in both arms continued in the randomized treatment phase as long as there was no protocol-defined disease progression. Methods: The European Organisation for the Research and Treatment of Cancer (EORTC) QoL Questionnaire–Core 30 (QLQ-C30) and Functional Assessment of Cancer Therapy–Lymphoma (FACT-Lym) questionnaires were assessed at baseline and weeks 8, 16, 24, and 48. EORTC QLQ-C30 consists of 30 items combined into 15 subscales (Global Health Status/QoL, 5 functioning subscales, and 9 symptom subscales; scores range from 0 to 100, and higher scores indicate better HRQoL and functioning but a worsening of symptoms). FACT-Lym consists of 42 items combined into 8 subscales (4 well-being subscales; 1 symptom subscale [LymS]; and 3 total scale scores: FACT-General [G], FACT-Lym trial outcome index [TOI], and FACT-Lym total; scores for the different subscales vary from 0–28 to 0–168, and higher scores indicate better outcomes). This analysis includes evaluable patients in the randomized treatment phase and assesses changes from baseline in HRQoL and MF symptom scores, including the EORTC subscales, LymS, and FACT total scores, which incorporate well-being and/or symptom subscales. Mixed-model analyses, adjusted for age, sex, baseline score, and prognostic risk category, are used to evaluate treatment differences at each time point and overall across time. Results: HRQoL and MF symptoms, on average, improved compared with baseline for patients receiving ruxolitinib, but remained the same or worsened for patients receiving BAT. Based on the EORTC QLQ-C30, the treatment differences in physical functioning, role functioning, fatigue, and appetite loss significantly favored ruxolitinib starting at week 8 (P

Description: Background : An emerging goal of tyrosine kinase inhibitor (TKI) therapy for patients with CML is to achieve sustained deep molecular response. Several factors, such as efficacy and tolerability of therapy and patient or disease characteristics, may impact treatment success. In this study, the correlation between specified prognostic factors and predicted molecular response levels after 1 year of treatment with nilotinib (NIL) 300 mg twice daily or imatinib (IM) 400 mg once daily was evaluated. Methods : Datafrom the ENESTnd trial comparing frontline treatment with NIL vs IM, in which BCR-ABL1 transcript levels were assessed every 3 months by real-time quantitative polymerase chain reaction on the International Scale (IS), were used to develop a statistical regression model to predict the BCR-ABL1IS category of a patient at any time point after 1 year of therapy. Potential predictors investigated were treatment, EMR status (BCR-ABL1IS ≤ 10% at 3 months), gender, age, Sokal risk score, BCR-ABL1IS categories from the previous 2 assessments, and the proportion of previous BCR-ABL1IS observations at or below MR4. BCR-ABL1IS transcript levels for patients in the NIL and IM arms of ENESTnd were stratified into 5 clinically relevant categories: ≤ 0.0032% (MR4.5), 〉 0.0032% to ≤ 0.01% (MR4), 〉 0.01% to ≤ 0.1%, 〉 0.1% to ≤ 10%, and 〉 10%. The model was specified to be a second-order Markov chain (to accommodate previous BCR-ABL1IS transcript levels) with ordinal prediction values (for ordered BCR-ABL1IS categorical outcomes). Results : Overall, 522 patients (NIL, n = 258; IM, n = 264) were included in the model, which contributed 5950 usable observations of BCR-ABL1IS transcript levels with corresponding values from the 2 prior assessments. Achievement of EMR (P = .0007), proportion of previous BCR-ABL1IS observations at or below MR4 (P 〈 .0001), and BCR-ABL1IS categories from the previous 2 assessments (both P〈 .0001) were significant predictors of BCR-ABL1IS category at any time after 1 year of treatment. In our model, neither Sokal risk score nor type of therapy was a significant predictor of BCR-ABL1IS category due to their high correlations with other factors included in the model and which are measured on treatment. For example, more patients in the NIL arm than in the IM arm achieved EMR (91% vs 67%, respectively), which accounted for a lack of model statistical significance for treatment type. Model predictions had good agreement with the observed trial data (Figure). Conclusion : Patients with CML who achieve EMR after initiating frontline TKI therapy have improved long-term treatment responses and survival outcomes. Our model also demonstrates that achievement of EMR is significantly associated with BCR-ABL1IS transcript levels after 1 year. These results add to the growing body of evidence that early response to TKI treatment should be carefully considered to ensure optimal long-term treatment success. Disclosures Saglio: Pfizer: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Novartis Pharmaceutical Corporation: Consultancy, Honoraria. Snedecor:Pharmerit International: Employment, Other: Institution received payment to conduct this study. Ji:Novartis Pharmaceuticals: Research Funding. Tai:Pharmerit International: Employment. Ray:Novartis Pharmaceutical Corporation/Rutgers University: Other: I am currently a fellow with Rutgers University, conducting my "field" experience at Novartis.. Mendelson:Novartis Pharmaceutical Corporation: Employment, Equity Ownership. Buchbinder:Novartis Pharmaceutical Corporation: Employment, Equity Ownership. Edrich:Novartis Pharma AG: Employment. Mahon:Novartis: Consultancy, Honoraria; Pfizer: Consultancy; ARIAD: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria.

Description: Background: With effective tyrosine kinase inhibitor (TKI) therapy, CML-CP disease burden can be reduced to minimal levels, and pts with CML-CP can have a life expectancy similar to that of the general population. Current guidelines recommend that pts continue TKI therapy indefinitely; however, in clinical trials (eg, the Stop Imatinib trials), some pts with deep molecular responses were able to suspend therapy and remain in TFR. This qualitative study assessed pt perspectives on CML treatment and TFR. Methods: Adults with CML-CP were recruited via third-party panels and interviewed by telephone (≈ 45 min) by trained staff from Oxford Outcomes using a standardized semistructured interview guide and open-ended questions. Some questions were not asked in all interviews; reported data are based on pts with responses for the indicated topic. Key themes and perceptions about TFR and potential impacts on health-related quality of life were identified by thematic analysis. Basic demographic information was also collected. Results: Of 40 participants, 68% were female and 68% were 〈 60 y old. Mean ± SD time since CML diagnosis was 5.2 y ± 4.6 y. Current CML treatment was imatinib (53%), dasatinib (25%), nilotinib (15%), or ponatinib (3%); 33% of pts were receiving second- or later-line TKI therapy; others were not receiving therapy due to a physician-supervised medication holiday (3%) or pregnancy (3%). Frequency of blood work (hematology/chemistry and/or molecular monitoring) for CML was every 3 mo for 60% of pts; 23% and 18% of pts had more frequent or less frequent blood work, respectively. Approximately half of pts (55%) had been told they achieved complete molecular response (CMR). Most pts (85%) did not experience/expect any positive physical impacts of CMR, but 68% said it would provide peace of mind that their CML was not progressing. Pts reported a variety of negative impacts of CML treatment, including financial burden (53%), limited ability to perform normal activities (social activities [25%], hobbies/physical activities [18%], work productivity [15%], and/or housework [10%]), and concern about long-term effects on their physical well-being (23%); 35% of pts reported low or no impact of CML treatment on their daily lives. Most pts (75%) reported having medication side effects, most commonly fatigue (60%), bone/joint pain (28%), nausea (18%), and active bowels/gastrointestinal issues (15%). Most pts (77%) said they had some understanding of TFR, and 58% were cautiously positive about attempting TFR. If their physician recommended it, 77% of pts ≥ 60 y old and 52% of pts 〈 60 y old said they would consider attempting TFR. The most frequently expressed expected positive impacts of TFR were relief of medication side effects (75%), reduced financial burden (58%), convenience (43%), positive emotional impact (43%), and increased activity level (30%). The most frequently expressed concerns about TFR included fear of resistance to therapy upon relapse (90%), low chance of successfully maintaining TFR (45%), emotional response to relapse and re-initiation of therapy (35%), desire for more frequent disease monitoring (33%), and fear of severe side effects upon re-initiation of therapy (33%). Some pts (28%) said their families may not want them to risk their health by attempting TFR. Among pts 〈 60 y old, 15% expressed concerns about the well-being of dependent children if they were to attempt TFR and relapse. Pts expressed a desire for more long-term data evaluating the safety of TFR in clinical trials. Pts reported a willingness to attempt TFR if there was at least a 10% chance of sustaining TFR for 2 y (range, 10%-100%), and the shortest duration of TFR they found acceptable ranged from “any amount of time” to 7 y. Conclusions: In this qualitative study, pts perceived many potential positive impacts of TFR, with relief of medication side effects being the most frequently expressed. Although TFR clinical trials have shown high rates of response to re-initiation of TKI therapy in pts with molecular relapse, a perceived risk of developing resistance to therapy was the most notable pt concern about TFR, and pts felt more clinical data are needed. Pt responses also revealed the importance of considering family when discussing TFR. With effective education and in the context of a controlled clinical trial, TFR may be an appropriate goal associated with meaningful pt benefits. More research into the pt perspective on TFR is needed. Disclosures Boquimpani: Bristol Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau. Off Label Use: Current CML treatment recommendations indicate that BCR-ABL TKI therapy should be administered indefinitely, and treatment-free remission (TFR) is an investigational approach that falls outside of current BCR-ABL TKI labels. However, this concept is not new, and promising preliminary results from several clinical trials of TFR have been reported. This abstract does not include any clinical data, but focuses on patient preferences and perceptions of TFR. . Szczudlo:Novartis: Employment, Equity Ownership. Mendelson:Novartis: Employment, Equity Ownership. Benjamin:Novartis Pharmaceuticals Corporation: Consultancy. Masszi:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Description: Introduction: Published trial data shows that ruxolitinib improves both splenomegaly-related and nonsplenomegaly-related constitutional symptoms in patients with intermediate-2 and high risk myelofibrosis (MF). However, few trial-based assessments of ruxolitinib in lower-risk MF patients have been conducted and no studies to date have made such assessments in a real-world population. In this study, we assessed changes in spleen size and constitutional symptoms during ruxolitinib treatment for lower-risk MF patients in real-world clinical settings. Methods: This was a retrospective, observational review of anonymized medical record data collected in January 2014 by 49 hematologists and oncologists in the United States. Patient inclusion criteria were: (1) diagnosed with lower-risk MF (International Prognostic Scoring System score of 0 or 1); (2) first treated with ruxolitinib ≥3 months before the medical record abstraction date; (3) ≥18 years of age at ruxolitinib initiation; (4) complete medical history from MF diagnosis until the medical record abstraction date; and (5) never enrolled in an MF-related interventional trial. Minimum quotas of n=50 and n=25 were set for intermediate-1 and low-risk patients, respectively, with a predetermined maximum of 110 patients in the combined total. Spleen size and constitutional symptoms were retrospectively observed at MF diagnosis, at ruxolitinib initiation, and at best response while on ruxolitinib. Spleen size was captured via predefined categories of no splenomegaly (spleen not palpable), very mild or mild splenomegaly (20 cm palpated). Symptoms of interest included those captured in the MPN Symptom Assessment Form (MPN-SAF), which were categorized as mild, moderate, or severe based on medical notes recorded at each time point. For this abstract, we present findings on the 7 most commonly observed MPN-SAF symptoms in our sample. This study was exploratory and used only descriptive analyses. Results: A total of 108 patients were included in the study (25 low-risk and 83 intermediate-1 patients). Ruxolitinib start dates spanned January 2012 – November 2013. All low-risk patients were ≤65 years of age, and nearly 80% of intermediate-1 patients were ≤65 years of age. The majority of patients in both risk groups (60% and 69%, respectively) were male. A higher proportion of intermediate-1 patients were positive for JAK2 V617F mutation (72%) than low-risk patients (56%). Most patients (92% of low-risk, 77% of intermediate-1) were still receiving ruxolitinib treatment at the medical record abstraction date. Median observed ruxolitinib exposure time was approximately 8 months in both risk groups. In low-risk patients, the combined proportion of patients with moderate or severe splenomegaly (≥10 cm palpated spleen) decreased from 64% at MF diagnosis to 16% at best response during ruxolitinib treatment (Figure 1a). Similar findings were observed for intermediate-1 patients: the proportion with moderate or severe splenomegaly decreased from 53% at MF diagnosis to 10% at best response (Figure 1b). General fatigue was the most commonly observed constitutional symptom in both low-risk and intermediate-1 patients (Figures 2a and 2b). Shifts in symptom severity from more severe to less severe were observed in both low-risk and intermediate-1 patients. Among low-risk patients with fatigue, the proportion with moderate or severe fatigue decreased from 90% at MF diagnosis to 37% at best ruxolitinib response; in intermediate-1 patients, the decrease was from 76% at MF diagnosis to 42% at best response. For most other symptoms, similar improvements in severity distribution were observed. Conclusions: Both low-risk and intermediate-1 MF patients experienced a substantial decrease in spleen size from MF diagnosis through ruxolitinib treatment in real-world clinical settings. Furthermore, for most symptoms examined, there was a distinct improvement in the distribution of symptom severity at the time of best response during ruxolitinib treatment. These findings suggest that lower-risk MF patients may benefit clinically from ruxolitinib treatment. Further studies are needed to assess adverse effects and evaluate the benefit-risk tradeoff of ruxolitinib. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Davis: Novartis Pharmaceuticals Corporation: Research Funding. Kaye:Novartis Pharmaceuticals Corporation: Research Funding. Cote:Novartis: Employment. Off Label Use: The study discusses use of ruxolitinib in patients with lower-risk (IPSS 0 or 1) myelofibrosis (MF) in real-world practice; currently ruxolitinib is only indicated in higher-risk MF (IPSS 〉1).. Gao:Novartis: Employment. Ronco:Novartis: Employment. Seifeldin:Novartis: Employment. Mendelson:Novartis: Employment.

Description: Abstract 4255 Background: Ruxolitinib demonstrated significant clinical benefits for patients (pts) with myelofibrosis (MF) in two phase 3 COMFORT studies. Nevertheless, in countries where health technology assessments are conducted, cost-effectiveness is an important consideration. Economic evaluations play an increasingly important role in reimbursement decisions for new treatments. To help inform such decisions, an evaluation of the cost-effectiveness (CE) of adding ruxolitinib as a treatment for MF was conducted from a Canadian societal perspective. Methods: A Markov model was built to estimate the costs, health outcomes, and CE of ruxolitinib compared with investigator-selected best available therapy (BAT), which included conventional therapies or no treatment. Data were derived from pts enrolled in the COMFORT-II study and included high-risk or intermediate-2–risk pts according to the International Working Group for Myelofibrosis Research and Treatment risk categorization. For this analysis, response was defined as a ≥ 35% reduction in spleen volume (COMFORT-II primary endpoint) or absence of constitutional symptoms. Survival assumptions were derived from a historical comparison of patients in the phase 1/2 study (Verstovsek et al, Blood. 2012) that showed a benefit for those achieving a ≥ 50% reduction in spleen length (equivalent to 35% spleen volume reduction). The model simulated disease progression in a cohort of pts with MF through 4 different health states with a 12-week cycle and a lifetime time horizon: 1) responder; 2) nonresponder; 3) leukemic transformation (LT); and 4) death. In each time cycle, pts incurred cost and utility estimates associated with their health state. The model considered the resource and utility implications arising from treatments aimed at directly treating splenomegaly, namely splenic irradiation and splenectomy. The outcomes of the Markov model included costs over the time horizon (drug costs, costs linked to the management of adverse events, other medical costs, indirect costs), life years, quality-adjusted life years (QALYs), and time spent as a responder to treatment. Both a 1-way sensitivity analysis and a probabilistic sensitivity analysis were performed, using estimated ranges and probability distributions for each input parameter. Results: The results showed that ruxolitinib-treated pts with MF had a better clinical outcome but at an increased cost. The total average lifetime cost of treating a pt receiving ruxolitinib was $494,859 CAD, with drug costs of $205,484 and other medical costs of $217,527, the majority of which were resource costs. The total average lifetime cost of treating a pt receiving BAT was $421,755, of which $59,289 was drug costs. Indirect costs were higher for BAT pts, at $96,458, exceeding the figure of $71,848 for ruxolitinib pts (Table). The clinical results showed longer average overall survival for pts receiving ruxolitinib compared with pts receiving BAT (Verstovsek et al, Blood. 2012). The ruxolitinib-treated pts had 4.01 QALYs compared with 2.82 QALYs for those in the BAT arm. The overall incremental CE ratio (ICER) was $61,444 per QALY. The key model drivers were the resource cost for nonresponders and improved mortality in the intermediate-2–risk group. Adopting a $100,000 per QALY willingness-to-pay threshold showed that 100% of the simulations for ruxolitinib therapy would be cost-effective compared with BAT for the treatment of MF. The mean ICER from the simulations was $59,216 per QALY, which was similar to the deterministic average of $61,444. Conclusions: There has been a high, unmet need for an effective therapeutic option for pts with MF. The COMFORT-II study has shown that ruxolitinib is clinically effective and superior to BAT at reducing splenomegaly and disease-related symptoms and improving health-related quality of life. The present analysis suggests that compared with BAT, ruxolitinib is an economically acceptable treatment option. Continued long-term evaluation of survival and potential reduction in rates of LT will also impact the future CE of ruxolitinib. Disclosures: El Ouagari: Novartis Pharma: Employment. Knight:Novartis Pharmaceuticals Corporation: Consultancy; Novartis Pharmaceuticals Canada: Consultancy. Mendelson:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership.

Description: Background : Tyrosine kinase inhibitors (TKIs) have dramatically improved outcomes in patients with Ph+ CML, in part by allowing achievement of sustained, low levels of BCR-ABL1 transcripts (quantified on the International Scale [IS]). TFR studies (eg, STIM, ENESTfreedom) evaluate whether some of these patients can stop TKI therapy and maintain a therapeutic molecular response off treatment. Here, we evaluated BCR-ABL1IS transcript levels of patients treated with frontline NIL 300 mg twice daily or IM 400 mg once daily for ≥ 1 year to predict time to TFR eligibility according to the ENESTfreedom trial criteria. Methods : A statistical model was developed to predict the probability of future premature treatment discontinuation (due to adverse events, progression, or suboptimal response) and BCR-ABL1IS transcript levels at any time point after 1 year of treatment. The 5-year data from the ENESTnd clinical trial, in which BCR-ABL1IS transcript levels were assessed every 3 months, were the basis for this model. Probabilities of premature treatment discontinuation were modeled using parametric survival methods; early molecular response (EMR; BCR-ABL1IS ≤ 10% at 3 months) status was used as a predictor. For patients remaining on treatment, a second-order Markov chain model was used to predict probabilities of BCR-ABL1IS transcript levels being in each of 5 clinically relevant categories (≤ 0.0032% [MR4.5 ], 〉 0.0032% to ≤ 0.01% [MR4 ], 〉 0.01% to ≤ 0.1%, 〉 0.1% to ≤ 10%, and 〉 10%) at any time point after 1 year of therapy. Probabilities were a function of EMR status, the proportion of previous BCR-ABL1IS observations at or below MR4, and BCR-ABL1IS categories from the previous 2 assessments. A simulated cohort of 1000 patients was created to match the distribution of EMR status and BCR-ABL1IS categories in the first year of therapy in each of the trial populations (NIL or IM). Premature treatment discontinuation and BCR-ABL1IS categories were randomly drawn at each 3-month interval based on their corresponding predicted probabilities. Time to eligibility criteria for TFR was defined as: last BCR-ABL1IS assessment of MR4.5, none of the prior 3 assessments worse than MR4, and no more than 2 of the prior 3 assessments between MR4 and MR4.5. Results : For years 2 to 5 of the ENESTnd trial, the observed distribution of BCR-ABL1IS categories over time had reasonable agreement with the computer-simulated cohort. Simulation results (Figure) demonstrated that more patients on NIL than on IM were eligible for TFR by year 5 (52% vs 38%, respectively) and by year 10 (72% vs 64%, respectively; P 〈 .0001 for both time points). Conclusion: Patients in our simulated cohort received a minimum of 3 years of frontline treatment with NIL or IM prior to TFR eligibility evaluation, similar to the current consensus in clinical disease management. Treatment with NIL resulted in significantly more patients becoming eligible for TFR by all time points vs treatment with IM. These data suggest that TFR as a therapeutic goal may be more attainable with NIL than IM. Studies evaluating the duration of TFR are presently being conducted. Disclosures Mahon: Novartis: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; ARIAD: Consultancy; Pfizer: Consultancy. Tran-Duy:Pharmerit International: Consultancy. Ray:Novartis Pharmaceutical Corporation/Rutgers University: Other: I am currently a fellow with Rutgers University, conducting my "field" experience at Novartis.. Mendelson:Novartis Pharmaceutical Corporation: Employment, Equity Ownership. Buchbinder:Novartis Pharmaceutical Corporation: Employment, Equity Ownership. Edrich:Novartis Pharma AG: Employment. Snedecor:Pharmerit International: Employment, Other: Institution received payment to conduct this study. Saglio:Pfizer: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Novartis Pharmaceutical Corporation: Consultancy, Honoraria.

Description: Background RUX is a JAK1/ JAK 2 inhibitor that has demonstrated improvements in splenomegaly, MF-related symptoms, and quality of life measures in the 2 phase 3 COMFORT studies. We recently demonstrated possible prognostic/predictive relationships between baseline (BL) cytokine levels and changes in spleen volume. Here, we evaluated the associations between cytokine levels and symptoms in COMFORT-II. Methods Ten symptoms, (fever, weight loss, easily tired, loss of appetite, pain, itching, sleeping well, lack of energy, night sweats, and trouble sleeping) were assessed at BL and weeks 8, 24, and 48 using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) instrument (0 to 4 scale). In this exploratory analysis, reverse coding of symptoms (except sleeping well) was performed. A high score reflects low symptom burden, and a positive change indicates improvement. Plasma samples were analyzed using Rules-Based Medicine's HumanMAP v1.6, measuring 89 cytokines at weeks 4, 24 and 48. Cytokines with ≥ 30% of values below lower limit of quantification were excluded. Two binary (0/1) variables were defined; Symptom Present = 1 when symptom score ² 2 and Improvement = 1 when change from BL symptom score 〉 0. Associations between Symptom Present and BL cytokine level were evaluated using univariate logistic regression (adjusted for IPSS risk and JAK2 mutation status), and for those associated at BL, the relationship between the fold-change in cytokine level (log2) and the Improvement over time was evaluated. Improvement and fold-change in a cytokine were considered as a bivariate response vector, and if the components of the response vector correlated it implied that the change in symptom score and change in cytokine were correlated over time. Results Of the 10 symptoms analyzed, 9 had BL associations with cytokines (Figure). Table shows cytokines and symptoms for which changes from BL were associated over time. At BL, lower ferritin levels were associated with itching and night sweats, lower leptin levels with weight loss, higher IL 1 receptor-α (IL1RA) levels with loss of appetite and higher CD40L, Pal1, and RANTES levels with not sleeping well. RUX-treated pts were more likely to have improvements in itching and night sweats than BAT-treated pts and had larger increases in ferritin levels over time. Larger changes in leptin levels with RUX treatment positively correlated with improvements in weight loss. IL1RA decreased significantly with time in the RUX arm and negatively correlated with loss of appetite, which improved over time. Conclusions Both BL levels and changes over time of various cytokines significantly correlated with MF-related symptoms. Ferritin levels appeared to be an important component of itching and night sweats. Additional analyses are required to explore the relationships between changes in cytokine levels and quality of life measures. These observations suggest a link between individual cytokines and symptoms in MF enhancing our understanding of the disease and providing a potential basis for future patient management tools. Disclosures: Squires: Novartis Phama AG: Employment. Harrison:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; YM Bioscience: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria; Shire: Speakers Bureau; S Bio: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Vannucchi:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Gisslinger:AOP Orphan Pharmaceuticals: Advisory Board Other, Honoraria; Novartis: Advisory Board, Advisory Board Other, Research Funding; Sanofi-Aventis: Advisory Board, Advisory Board Other, Honoraria; Shire: Advisory Board, Advisory Board Other, Honoraria; Celgene: Advisory Board Other, Honoraria; Janseen: Advisory Board, Advisory Board Other, Honoraria. Passamonti:Sanofi: Honoraria; Novartis: Honoraria. Al-Ali:Novartis: Consultancy, Honoraria; Celgene: Honoraria, Research Funding. Kiladjian:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees; AOP Orphan: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Marker:Novartis: Employment. Mendelson:Novartis: Employment. Stalbovskaya:Novartis: Employment, Equity Ownership. Cervantes:Novartis: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Sanofi Aventis: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Knoops:Novartis: Consultancy; BMS: Consultancy.