MF-related Symptoms Research Articles

Patient Characteristics, Treatment Patterns, and Health Outcomes in a Real-World Population of Patients with Myelofibrosis Treated with Fedratinib

Introduction: Myelofibrosis (MF) is a type of myeloproliferative neoplasm characterized by bone marrow fibrosis, splenomegaly, progressive anemia, and debilitating constitutional symptoms. Fedratinib (FEDR) is a selective Janus kinase-2 inhibitor (JAK2i) approved for the treatment of adult patients with intermediate (int)-2 or high-risk primary or secondary MF. Patients with MF have a median overall survival of 5-7 years; however, prior to FEDR approval, ruxolitinib (RUX) was the only approved JAK2i for MF treatment, with the majority of patients discontinuing RUX within 3 years of treatment initiation (Harrison C, et al. Ann Hematol 2020;99:1177-1191). Given the current availability and use of FEDR, the primary study objective was to describe demographics, clinical characteristics, and treatment patterns of patients with MF receiving FEDR in real-world practice settings after prior RUX treatment. A secondary objective was to assess changes in MF-related symptoms and spleen size during FEDR treatment. Methods: We report interim data from a medical records review of adult patients with MF who received FEDR treatment after RUX discontinuation (due to treatment refractoriness, relapse, or intolerance) in Canada (CAN), Germany (GER), and the United Kingdom (UK). Data collection is ongoing, and we present data abstracted from March through May 2023. Patients were required to have an int-2 or high-risk MF diagnosis at FEDR initiation and to have initiated FEDR after date of first availability in each country (CAN: Sep 21, 2020, GER: Feb 9, 2021, UK: Nov 1, 2021) up to 6 months prior to data abstraction. Patients who received allogenic, hematopoietic cell transplantation after initial MF diagnosis or participated in a JAK2i trial were excluded. Spleen size evaluation through palpation at FEDR initiation and at least once within the first 6 months of FEDR use was required. Study outcomes measured were patient characteristics, treatment patterns, MF-related symptoms, and spleen size evaluations. Descriptive statistics are reported. Results: A total of 58 patients (CAN: 13, GER: 32, UK: 13) were included in the analysis. Median age at MF diagnosis and FEDR initiation was 67.9 and 71.8 years, respectively. 65.5% of patients were male, and 91.4% were White. Most patients were diagnosed with primary MF (60.3%) and had JAK2 V617F mutation (84.5%). Among patients who had a bone marrow biopsy (n = 51), 58.8% had grade 2 bone marrow fibrosis. Mean baseline Charlson Comorbidity Index score was 2.5. Median time from MF diagnosis and RUX treatment discontinuation to FEDR initiation was 34.0 months and 0.7 months, respectively. Most common reasons for FEDR initiation were splenomegaly (75.9%), RUX failure (67.2%), and to achieve symptom control (63.8%) (Table). Over a median follow-up of 12.1 months after FEDR initiation, 19 patients (32.7%) discontinued FEDR treatment with a median treatment duration of 7.7 months. Among the 39 patients taking FEDR at data abstraction, median treatment duration was 12.5 months. At FEDR initiation, 48.3% and 51.7% had int-2 risk and high-risk MF, respectively. The most common MF-related symptoms presented were fatigue (74.1%), abdominal discomfort (63.8%), and night sweats (46.6%) (Table). 62.1% of patients initiated FEDR treatment at the recommended therapeutic dose of 400 mg, and 74.1% were receiving 400 mg at end of follow-up/treatment discontinuation. Among patients with ≥ 1 FEDR dose change, titration to therapeutic dose (68.4%) was the most common reason for their first dose change. MF-related symptoms decreased in the first 6 months of FEDR treatment, including fatigue (74.1% [at FEDR initiation] reduced to 52.8% [at 6 months after FEDR initiation]), abdominal discomfort (63.8% reduced to 11.3%), and night sweats (46.6% reduced to 3.8%). The proportion of patients with severe (palpable spleen:> 20 cm) and moderate splenomegaly (palpable spleen: 11-20 cm) decreased from FEDR initiation to 6 months after initiation (severe splenomegaly: 32.8% to 7.5%, moderate splenomegaly: 55.2% to 15.1%) (Figure). Conclusion: Thepatients included in this study exhibited a significant level of illness . In this interim analysis, patients treated with FEDR following RUX treatment failure showed resolution of MF-related symptoms and a marked decrease in splenomegaly in the initial 6-month period, demonstrating the real-world effectiveness of FEDR treatment in patients with MF.

Transform-1: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, International Phase 3 Study of Navitoclax in Combination with Ruxolitinib Versus Ruxolitinib Plus Placebo in Patients with Untreated Myelofibrosis

Background: Janus kinase inhibitors (JAKis) provide symptom improvement and spleen volume reduction in patients with primary, post-polycythemia vera, and post-essential thrombocythemia myelofibrosis (MF). There remains a substantial unmet need for therapies that alter disease trajectory, improve outcomes, and enhance survival. The COMFORT-1 and -2 studies established JAKi monotherapy as standard-of-care with spleen volume reduction of ≥35% at Week 24 (SVR 35W24) of 42% and SVR 35W48 of 29%, respectively. In combination with the JAKi ruxolitinib, navitoclax, an orally available inhibitor of antiapoptotic B-cell lymphoma 2 proteins (BCL-X L, BCL-2, BCL-W), was shown to have pronounced antitumor activity in patients with MF in the phase 2 REFINE trial (NCT03222609). TRANSFORM-1 is an ongoing, phase 3, double-blind, placebo-controlled, multicenter, international study evaluating the safety and efficacy of navitoclax plus ruxolitinib (NAV + RUX) compared with placebo plus ruxolitinib (PBO + RUX) in JAK2i-naïve adults with MF. Methods: TRANSFORM-1 (NCT04472598) enrolled adult patients with intermediate-2 or high-risk MF with measurable splenomegaly, evidence of MF-related symptoms, no prior JAK2i treatment, and ECOG Performance Score ≤2. Patients were randomized 1:1 to receive NAV (starting dose of 200 mg [platelet {PLT} >150 × 10 9/L] or 100 mg escalated to 200 mg once daily if tolerated after ≥7 days [PLT ≤150 × 10 9/L]) or PBO, plus RUX at label dose, based on stratification factors of intermediate-2 vs high-risk MF and PLT ≤200 × 10 9/L vs >200 × 10 9/L. The primary endpoint was SVR 35W24. Secondary endpoints included change in total symptom score at Week 24 (TSS W24) assessed using 7-item MFSAF v4.0 (scale 0-70), SVR 35 at any time, duration of SVR 35, anemia response (per International Working Group criteria), reduction in marrow fibrosis, overall survival, leukemia-free survival, reduction in PROMIS Fatigue scale, and improvement in EORTC QLQ-C30 physical functioning scale. Exploratory endpoints include progression-free survival. Results: At data cutoff, April 13, 2023, 252 patients were enrolled with a median (range) follow-up of 14.9 (0.0-29.5) months; 125 patients were randomized to receive NAV + RUX and 127 to receive PBO + RUX. Most patients were male (57%), median (range) age was 69 (37-87) years, and patient demographics were similar between treatment arms ( Table 1). TRANSFORM-1 met its primary endpoint, with 79 patients (63.2%) in the NAV + RUX arm achieving SVR 35W24 compared with 40 patients (31.5%) in the PBO + RUX arm ( P<0.0001). Notably, SVR 35 at any time was achieved by 96 patients (77%) with NAV + RUX compared with 53 patients (42%) with PBO + RUX. Median (range) time to SVR 35 response was 12.3 (10.1-48.3) weeks with NAV + RUX versus 12.4 (11.3-72.3) weeks with PBO + RUX. Median duration of SVR 35 was not reached (NR) in the NAV + RUX arm compared with 19.4 months (95% CI 16.8, NR) in the PBO + RUX arm. At Week 24, the mean change in TSS from baseline was -9.7 (95% CI: -11.8, -7.6) with NAV + RUX compared with -11.1 (95% CI: -13.2, -9.1) with PBO + RUX arm ( P=0.2852). Grade ≥3 adverse events (AEs) were experienced by 85% of patients with NAV + RUX and 70% with PBO + RUX. The most common AEs (>30% of patients receiving NAV; Table 2) were thrombocytopenia, anemia, diarrhea, and neutropenia. Serious AEs were experienced by 26% of patients with NAV + RUX and 32% with PBO + RUX, including anemia (NAV + RUX: n=2; PBO + RUX: n=1), thrombocytopenia (NAV + RUX: n=2), and neutropenia (NAV + RUX: n=1). With NAV + RUX, AEs led to NAV dose reduction in 101 (81%) patients and NAV interruption in 87 (70%) patients of which 83 (67%) and 65 (52%) were due to thrombocytopenia, respectively. Of all enrolled patients, 83 (33%) discontinued study treatment; most common (>5% total patients) reason for NAV/PBO discontinuation were AEs (n=32; 39% of discontinuations) and physician decision (n=14; 17% of discontinuations). In each arm, 13 (10%) patients died; 6 with NAV + RUX and 5 with PBO + RUX died ≤30 days post-final dose. Conclusions: This first randomized trial in JAKi-naïve MF with NAV + RUX combination led to an SVR 35W24 rate that was twice as high as PBO + RUX ( P<0.0001). The responses were durable; AEs of thrombocytopenia and anemia were common but manageable with dose modification without any clinically significant sequalae. Additional evaluation is ongoing.

Patient-reported Outcomes and Quality of Life in Anemic and Symptomatic Patients With Myelofibrosis: Results From the MOMENTUM Study.

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm that typically manifests with debilitating symptoms that progressively worsen, negatively impacting patients' quality of life. Fatigue is a multifactorial and burdensome MF-related symptom due to its severity, persistence, and prevalence, with anemia a contributing factor and major unmet need. Clinical trials of the Janus kinase (JAK)1/JAK2/activin A receptor type 1 inhibitor momelotinib have shown consistent anemia benefits, in addition to improvements in MF-related symptoms. The phase 3 MOMENTUM trial in symptomatic and anemic patients met its primary end point, with a greater proportion having a Myelofibrosis Symptom Assessment Form (MFSAF) Total Symptom Score (TSS) reduction ≥50% at week 24 with momelotinib versus danazol. To support the positive primary end point result, we conducted longitudinal, responder, and time-to-event analyses of patient-reported outcomes from MOMENTUM, as measured by the MFSAF, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and Patient-Reported Outcomes Measurement Information System (PROMIS) assessments. These analyses demonstrated rapid and durable response benefits with momelotinib, with achievement of first TSS response by day 29 and continued improvement over time. Improvements favored momelotinib versus danazol for each MFSAF individual item, and greater improvements were observed for disease- and cancer-related fatigue and physical functioning at week 24, with significant results for multiple items/domains across the 3 assessments. These findings are consistent in demonstrating that momelotinib provides substantial symptom benefit.

Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are intolerant to ruxolitinib: A single-arm, open-label, phase 2, multicenter study.

Although ruxolitinib improves splenomegaly and constitutional symptoms in patients with myelofibrosis (MF), a substantial proportion of patients discontinue ruxolitinib because of intolerance. This phase 2 trial investigated the safety and efficacy of jaktinib, a novel JAK inhibitor in patients with ruxolitinib-intolerant MF. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) at week 24. The secondary endpoints included change of MF-related symptoms, anemic response, and safety profiles. Between December 18, 2019, and November 24, 2021, 51 patients were enrolled, 45 treated with jaktinib 100 mg bid (100 mg bid group) and six received non-100 mg bid doses (non-100 mg bid group). The SVR35 at week 24 in the 100 mg bid group was 43.2% (19/44, 95% CI 29.7%-57.8%). There were 41.9% (13/31) of transfusion-independent patients with hemoglobin (HGB) ≤100 g/L who had HGB elevation ≥20 g/L within 24 weeks. The proportion of patients with a ≥50% decrease in the total symptom score (TSS 50) at week 24 was 61.8% (21/34). The most commonly reported grade ≥3 treatment-emergent adverse events (TEAEs) in the 100 mg bid group were anemia 31.1%, thrombocytopenia 22.2%, and infectious pneumonia 17.8%. A total of 16 (35.6%) in the 100 mg bid group had serious adverse events, and 4 (8.9%) were considered possibly drug related. These results indicate jaktinib can provide a treatment option for patients with MF who are intolerant to ruxolitinib.

The Impact of Momelotinib on Patient Reported Quality of Life for Symptomatic and Anemic Patients with Myelofibrosis: Results from the Phase 3 Momentum Study

Introduction Disease-related inflammation, anemia and splenomegaly contribute to a host of burdensome symptoms in patients with myelofibrosis (MF), including fatigue, bone pain, night sweats, and others, which can negatively impact health-related quality of life (HRQoL). There are no approved treatments for patients with intermediate- and high-risk MF that specifically target anemia, and approved MF therapies for splenomegaly and symptoms often exacerbate anemia. Momelotinib (MMB) is a Janus kinase (JAK) 1, JAK2, and activin A receptor type 1 (ACVR1) inhibitor with demonstrated symptom, spleen, and anemia benefits in patients with MF. MOMENTUM, a phase 3 study in symptomatic, anemic patients with MF who were previously treated with a JAKi, showed that MMB significantly improved disease-related symptoms compared to danazol (DAN) (24.6% vs 9.2%) as measured by achieving at least a 50% reduction in total symptom score (TSS50) at week 24 compared to baseline. Herein we report the results of patient-reported health status and HRQoL analyses, including impact on fatigue and physical function, for patients treated with MMB compared to DAN in the MOMENTUM study. Methods Patient-reported outcome (PRO) analyses were performed for the following assessments in the intent-to-treat (ITT) population: Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 TSS and individual items, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)-derived scales and items, and Patient-Reported Outcomes Measurement Information System (PROMIS) short form physical function total score 10b and additional PROMIS bank items. Analyses of PRO response were summarized by corresponding meaningful change threshold (MCT) for each PRO. Longitudinal change from baseline scores were analyzed using mixed model for repeated measures (MMRM). Longitudinal responder analyses were performed by generalized estimating equation (GEE) after multiple imputation for missing scores. Odds ratio (OR) for response, 95% confidence interval (CI), and p-value were presented as the treatment effect (MMB vs DAN). Time to first response was analyzed using the Kaplan-Meier method. A stratified log-rank test was performed to compare treatment arms, and hazard ratios (HR) were estimated from a stratified Cox regression model. Results Proportionally greater improvements in MF-related symptoms, physical function, and global quality of life were observed with MMB versus DAN as measured at week 24 by the MFSAF, PROMIS, and EORTC QLQ-C30 questionnaires, respectively. Improvements in all MFSAF individual item scores from baseline at week 24 were greater in the MMB group than in the DAN group based on median scores (Figure 1) and MMRM analysis (Table 1), with the greatest treatment differences noted for night sweats, abdominal discomfort, bone pain, and rib pain, favoring MMB. Longitudinal MFSAF TSS response analysis indicated a higher likelihood of response for patients in the MMB group: an overall OR of 2.50 throughout the 24-week randomized treatment period. HRs for response were greater than 1 (ranging from 1.47 - 3.82) in the time to first response analysis for MFSAF TSS and individual items, excluding itching (0.77), indicating a faster symptom response for more patients in the MMB group for TSS and 6 of 7 individual items. Responder analyses showed that the proportion improved for fatigue was greater in the MMB group based on MFSAF fatigue (18.5% MMB, 9.2% DAN) and EORTC QLQ-C30 fatigue (41.5% MMB, 21.5% DAN), where missing data was considered nonresponse. Consistent with these results, responder analysis using the PROMIS assessments related to physical function also favored MMB (17.7% MMB, 4.6% DAN). This trend was supported by shorter times to first response for physical function in more patients in the MMB group versus the DAN group (HR = 1.93, 95% CI 0.95, 3.91). Improvement in global quality of life as measured by EORTC QLQ-C30 was also greater in the MMB group with a proportion difference of 14.6% between MMB and DAN (95% CI: 1.5-27.7%; p = 0.04). Conclusions Consistent with the positive primary endpoint (TSS50) result of the MOMENTUM study, these responder, longitudinal, and time-to-event analyses demonstrate that MMB provides comprehensive improvements in disease-related symptoms with associated improvement in physical function and overall HRQoL compared with DAN in patients with MF. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Disease Progression and Leukemic Transformation in Patients With Lower-Risk Myelofibrosis (MF): An Analysis from MOST

Background: Progressive disease (PD) in MF is associated with increased bone marrow fibrosis, worsening anemia, and an increase in circulating blasts and can result in leukemic transformation (LT). LT is a rare (~11% incidence) but fatal complication of MF with a mortality rate of 97% and a median survival of 3.6 months. Real-world data regarding PD and LT in lower-risk MF are limited. This analysis from the Myelofibrosis and Essential Thrombocythemia Observational Study (MOST; NCT02953704) describes the incidence of PD, including LT, in patients with lower-risk MF and compares the baseline characteristics of patients who progressed vs those who did not. Methods: MOST is a longitudinal, noninterventional, prospective, observational study of patients with clinical diagnoses of MF or essential thrombocythemia enrolled at clinical practices in the US. Patients included in this analysis (≥18 years) had low-risk or intermediate-1 (INT-1)-risk MF (by age >65 years alone) stratified by the Dynamic International Prognostic Scoring System (Blood. 2010;115:1703) at enrollment and were followed for at least 3 years. Baseline data were collected as previously described (Gerds A. Clin Lymphoma Myeloma Leuk. 2022;22:e532-e540). PD was defined as physician-reported PD, LT, and/or death by reason of progression. Results: Of the 232 patients with MF enrolled in MOST, 204 patients (low-risk: n=84, 41.2%; INT-1-risk: n=120, 58.8%) were included in this analysis (data cutoff: July 5, 2022). The median (range) time from MF diagnosis to enrollment was 1.8 (0-38) years and the median (range) enrollment duration was 4.2 (3.3-5.4) years. Of 193 patients with available data on disease progression, 46 patients (23.8%) had physician-reported PD; of these, 18 (22.0%) were low-risk and 28 (25.2%) were INT-1-risk. The most commonly reported indicator was change in hematologic parameters (n=27 [58.7%]), followed by change in spleen size (n=19 [41.3%]), MF-related symptoms (n=16 [34.8%]), and blast counts (n=8 [17.4%]). LT was reported in 15 patients (7.8%); of these 4 (4.9%) were low-risk and 11 (9.9%) were INT-1-risk. Death by any cause was reported in 30 patients (14.7%; PD, n=16, without PD, n=9; unknown PD, n=5). Patient baseline characteristics are shown in Table 1. Patients who had PD were older than patients without (median [range] age: PD, 70.0 [35-88] vs without PD, 66.5 [35-88] years). Bone marrow biopsy/aspiration and mutation tests at diagnosis were reported in 98.3% and 80.7% of patients with PD and in 91.8% and 82.8% of patients without PD, respectively. Significant differences in the symptomatology of patients with PD vs without PD were not detected at time of enrollment. More than half of patients with PD and without PD were receiving MF-directed monotherapy at enrollment (59.3% vs 55.2%). The most common monotherapies received in patients with PD vs without PD were hydroxyurea (15.3% vs 28.4%) and ruxolitinib (37.3% vs 17.9%). Six patients (PD, n=3; without PD, n=3) received >1 MF-directed therapy. Conclusion: This real-world analysis of data from patients enrolled in MOST describes the disease evolution of patients with lower-risk MF. After ~3 years of follow-up, a relatively high proportion of patients in this population had physician-reported PD or LT (23.8% and 7.8%, respectively). Baseline characteristics and symptoms did not differ between those who progressed and those who did not; however, further analysis of molecular and post-baseline data may provide insight into risk factors for disease progression in this lower-risk population. Identification of patients with higher risk of PD is likely to improve disease management and outcomes for patients with lower-risk MF. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Real-World Outcomes of Ruxolitinib in Patients With Myelofibrosis Focusing on Red Blood Cell Transfusion: A Multicenter Study From the MPN Working Party of the Korean Society of Hematology

Introduction/BackgroundRuxolitinib is an established treatment for myelofibrosis (MF) that has demonstrated clinical benefit by reducing spleen size and debilitating MF-related symptoms. However, despite the efficacy of ruxolitinib, anemia remains a major adverse event that causes dose modification or discontinuation in real-world practice. Additionally, dependence on red blood cell (RBC) transfusion (TF) is common during treatment; therefore, we explored the outcome of ruxolitinib therapy with a primary focus on RBC TF. Patients/MethodsWe retrospectively reviewed the medical records of 123 MF patients treated with ruxolitinib between January 2012 and April 2020 at eight academic centers in Korea. ResultsAt ruxolitinib initiation, 38 patients (30.9%) underwent ≥ 2 units of RBC TF over 8 weeks. The most common reason for permanent discontinuation was intolerant anemia (10/63, 15.9%). The most common reasons for temporary interruption were nonhematologic toxicity (26/55, 21.1%), anemia (23/55, 18.7%) and thrombocytopenia (13/55, 10.6%). Among the 123 patients in the study, 57 (46.3%), 42 (34.1%), and 40 patients (32.5%) who were receiving or stopped ruxolitinib therapy had a status of RBC TF dependence, long-term RBC TF dependence, or severe RBC TF dependence, respectively. The presence of ≥ 2 units of RBC transfusion over 8 weeks at ruxolitinib initiation was an independent risk factor for persistent RBC TF dependence. ConclusionThe requirement for RBC TF is commonly encountered during treatment of MF with ruxolitinib, particularly among those with pre-existing ≥ 2 units of RBC TF over 8 weeks. For those patients, overcoming the barrier of maintenance TF is demanding.

P1060: REAL-WORLD CLINICAL OUTCOMES AFTER 3 AND 6 MONTHS OF TREATMENT WITH FEDRATINIB FOLLOWING RUXOLITINIB FAILURE

Background: Relief of symptoms and splenomegaly is an important treatment (Tx) goal for patients with myelofibrosis (MF). Fedratinib (FEDR) and ruxolitinib (RUX) are approved in the USA for Intermediate (Int)- or High-risk (HR) primary or secondary MF. Aims: To describe spleen size, and hematologic and MF-specific symptoms, during the first 6 months of FEDR therapy after prior Tx with RUX in US clinical practices. Methods: Adults with Int- or HR MF who initiated FEDR on or after August 16, 2019 (FEDR approval date) and with ≥90 days of follow-up were identified from community oncology practices. Eligible patients were those treated with RUX and then FEDR, who had spleen palpation at FEDR initiation, and who had completed ≥1 cycle of FEDR. Treating physicians completed electronic case report forms for the selected eligible patients, extracting patient characteristics, Tx pattern data, and clinical outcomes such as spleen size, MF-related symptoms per the Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0), hemoglobin (Hb), and platelet and white blood cell (WBC) counts, at each visit in the first 6 months of FEDR Tx. Data were collected from February to March 2021. Mean spleen size, symptom count, Hb, and platelet and WBC counts at FEDR initiation vs at 3 and 6 months post-FEDR were compared via paired 2-sided t-test. Percentage reduction in spleen size and proportion of transfusion-dependent patients between FEDR initiation and 3 and 6 months post-FEDR were compared via 1-sided chi-square test. Only patients assessed at FEDR initiation (with palpable spleen or complete blood count available) and with a corresponding assessment at 3 or 6 months were included in the comparative analysis. Results: Among 150 eligible patients, the mean age at FEDR initiation was 68 years (range, 36–85). Median duration of RUX Tx prior to FEDR was 7.6 months (range, 0.7–65.5). At FEDR initiation, MF risk was categorized as International Prognostic Scoring System (IPSS)/Dynamic IPSS HR in 43% of patients, Int-2 in 37%, Int-1 in 9%, and unknown in 10%. A total of 74% of patients started FEDR at the recommended dosage of 400 mg daily. Median duration of post-FEDR follow-up was 5.1 months (IQR, 3.0–17.3) for patients initiated at FEDR 400 mg daily and 4.4 months (IQR, 3.0–14.3) for those initiating at <400 mg daily. At data cutoff, 55% of patients were still on FEDR. The primary reason for FEDR discontinuation was disease progression (43%). Mean duration of FEDR Tx was 4.7 months. Of 67 patients who discontinued FEDR, 44 were deceased at data cutoff. At FEDR initiation, 88% of patients had palpable spleen; mean spleen size was 16.0 cm (standard deviation [SD] 5.8) above the costal margin, which decreased to 13.2 cm (SD 7.9) at 3 months (P=0.0001) and 7.2 cm (SD 7.4) at 6 months (P=0.012). Mean number of MF-related symptoms declined significantly at 3 and 6 months; mean platelet count increased significantly at 6 months, from 160×109/L to 186×109/L (Table). Overall, 65.2% of patients experienced spleen size reduction, 18.8% had no change, and 16.0% had an increase. Mean best percentage change in spleen size was −29.2% (median −9.8%); complete resolution of palpable spleen occurred in 21% of patients. Image:Summary/Conclusion: This study illustrates the real-world effectiveness of FEDR after RUX failure in patients with Int- or HR MF. FEDR provided significant reductions in spleen size and reported number of MF-related symptoms after 3 months of Tx, including complete spleen responses. Greater benefits were observed with longer Tx duration.

A phase 1, open-label, dose-escalation study of selinexor plus ruxolitinib in patients with treatment-naïve myelofibrosis.

7060 Background: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by unregulated, clonal proliferation of a hematopoietic stem cells in the bone marrow and is commonly associated with gene mutations in JAK2, CALR, or MPL. Front-line therapy may include the JAK1/2 inhibitor ruxolitinib (RUX), resulting in spleen volume reductions and improvement in MF-related symptoms. Despite the therapeutic effect of RUX, most patients (pts) eventually progress and thus novel combinations are required to increase responses and delay progression. Selinexor (SEL) is an oral selective inhibitor of nuclear export (SINE) compound, specifically inhibiting exportin-1 (XPO1), and currently approved for treatment of multiple myeloma and diffuse large B-cell lymphoma. Significant activity of SEL in combination with RUX has been shown in preclinical studies, and SEL monotherapy in MF refractory to JAK inhibitors demonstrated robust clinical activity and a tolerable safety profile (NCT03627403). Here, we present the initial results of a phase 1 dose escalation study of the combination SEL and RUX in treatment-naïve MF. Methods: The ongoing multicenter, open-label, Phase 1/2 study (NCT04562389) is evaluating the efficacy and safety of SEL plus RUX in JAKi-naïve MF pts. Two dose levels of SEL were evaluated, 40mg and 60mg once-weekly (QW) plus RUX twice daily (BID) as per label in 28-day cycles, using a 3+3 design. All pts received 5-HT3 antagonist for nausea prophylaxis. Primary objectives include safety, maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and preliminary efficacy. Secondary objectives include spleen, symptom, and anemia response, and OS. Results: As of 31 Jan 2022, 10 pts have been dosed in 2 dose levels (40mg (n = 3), and 60mg (n = 7) SEL QW plus RUX). RUX starting dose was 20 mg in 8 pts, 15 mg in one patient and 10 mg in one patient. The median age was 64 (range 45-76). Seven pts had primary MF and 3 had post-ET MF. DIPSS risk category was int-1 (n = 4), int-2 (n = 4) and high risk (n = 2). No dose limiting toxicities have been reported at either dose levels of SEL. One patient required dose interruption due to dizziness and later discontinued treatment due to new onset of atrial fibrillation and pulmonary hypertension (unrelated to SEL and RUX) after 5 months of therapy. All other pts remain on study. There was no grade 3 neutropenia or thrombocytopenia observed. Hemoglobin level was maintained without any significant worsening. The most common treatment-emergent adverse event was low grade nausea (30%). All pts experienced improvement in their white blood cell count. Four of the first 5 evaluable pts demonstrated ≥35% spleen volume reduction at week 12. Conclusions: The combination of SEL and RUX has been well-tolerated and with a manageable side effect profile. No dose limiting toxicities were observed in pts with treatment-naïve MF in cohort 1 of once weekly oral SEL 40 and 60 mg with RUX. Clinical trial information: NCT04562389.

Real-life ruxolitinib experience in intermediate-risk myelofibrosis.

BackgroundIn this retrospective cohort of patients with primary, post-polycythemia vera, or post-essential thrombocythemia myelofibrosis, 57 patients with MF who received ruxolitinib for MF-related symptoms or symptomatic splenomegaly were evaluated.MethodsThe median age of the patients in this cohort was approximately 58 years. Of these, there were 33 patients (57.9%) in INT-1, 23 patients (40.4%) in INT-2, and 1 patient (1.8%) at high risk. Overall, spleen size reduction of at least 35% (spleen response) was achieved in 56.6% and 63.3% of all cohort and INT-1 risk at any time, respectively.ResultsSymptom response and clinical improvement were observed in 21.7% and 60.7% of patients, respectively. Anemia and thrombocytopenia were prevalent, but manageable. About 73.7% of patients continued treatment during a median follow-up of 22 months. Two-year OS probability was approximately 84.5% (95% CI, 63.1‒94.0%) and 62.3% (95% CI, 37.5‒79.6%) for the intermediate-1 and -2 risk groups, respectively.ConclusionReal-life experience in a community-based hospital confirms the efficacy and safety profile of ruxolitinib in intermediate-risk myelofibrosis. Treatment discontinuation rates were lower than those in clinical trials.

Peripheral Blasts Are Associated with Response to Ruxolitinib and Outcome in Patients with Chronic-Phase Myelofibrosis

Peripheral Blasts Are Associated with Response to Ruxolitinib and Outcome in Patients with Chronic-Phase Myelofibrosis

Community Versus Academic Practice in Essential Thrombocythemia and Myelofibrosis: Differences in Clinical Characteristics, Diagnosis, Treatment Patterns, and Symptom Burden (Analysis of Data from the MOST Study)

Community Versus Academic Practice in Essential Thrombocythemia and Myelofibrosis: Differences in Clinical Characteristics, Diagnosis, Treatment Patterns, and Symptom Burden (Analysis of Data from the MOST Study)

Dynamic Stromal Changes in Myelofibrosis Patients Pre/Post JAK Inhibition Is Revealed in Clinically Archived Bone Marrow Biopsies By Smooth Muscle Actin (SMA)-CD34 Dual Immunohistochemistry

The natural history of BCR-ABL1 negative myeloproliferative neoplasms (MPNs) is progression towards an overt myelofibrotic (MF) phase with variable risk to develop secondary acute myeloid leukemia. Current treatments include Janus kinase inhibitors (JAKi) which can temporarily alleviate MF-related symptoms but are non-curative and most patients eventually progress to a more advanced stage. Given the negative prognostic impact of bone marrow fibrosis in MPNs and generally poor outcome post JAKi failure, it would be important to identify in situ biomarkers that address the initiation, perpetuation and early reversal of the fibrotic reaction.The current clinical standard for bone marrow fibrosis assessment involves reticulin/trichrome stains that detect relatively static extracellular matrix products rather than the fibrosis driving cells directly. To address this, we have developed a smooth muscle actin stromal-vascular (SMA-CD34) dual immunohistochemical (IHC) technique amenable to morphologic scoring and complemented with a CellProfiler image analysis pipeline. SMA was prioritized over other validated stromal IHC markers given work by others in experimental models demonstrating SMA+ myofibroblasts to be the differentiated output of critical fibrosis inducing Gli1+ ‘driver’ mesenchymal stem/progenitor cells in MPN.Herein, we demonstrate the feasibility of our translational approach using a clinically annotated cohort of MF patients from the Princess Margaret Cancer Centre MPN Registry. After selecting for high quality (>1.0 cm) paired pre and post JAKi biopsies amenable to image and transcriptome-based analysis, the pilot cohort was comprised of 13 cases with 38% high-risk, 54% intermediate-2 and 8% intermediate-1 risk by DIPSS. Driver mutations were JAK2 V617F (77%), CALR (15%) and other (8%). JAKi therapies included ruxolitinib (31%) + pelabresib (23%), momelotinib (15%), itacitinib (15%) and pacritinib (8%).The SMA-CD34 stromal assessment at baseline revealed distinct interstitial myofibroblast patterns and vascular perturbations not captured by conventional clinical hematopathology assessment (e.g. SMA+ dilated sinusoids). A SMA-CD34 scoring system was developed using a 4-point scale representing normal (0 pts), increased vascularity (1 pt), focal interstitial SMA (2 pts), multifocal interstitial SMA (3 pts) and diffuse SMA (4 pts). Scoring was then performed by blinded hematopathologists. A trend towards JAK2 mutated MF cases demonstrating higher SMA grade at baseline was noted. Interestingly, variable trajectories in SMA scores emerged following treatment with JAKi. Specifically, SMA signals had increased in 15%, decreased in 46% and were stable in 38% post-JAKi when using a morphologic SMA grading scheme. When compared to reticulin fibrosis, the severity of SMA signals had diverged in 1/3 of the cases (e.g. SMA grade decreased, reticulin grade stable).To further complement the SMA-CD34 morphologic grading, a CellProfiler image analysis pipeline was developed yielding a non-vessel associated normalized SMA area metric as a supervised correlate of the clinical SMA scoring system (R 2 = 0.68). Additional supervised and unsupervised bioinformatic approaches for clustering of relevant SMA-CD34 features including an algorithm that informs SMA spatial patterns with respect to niche elements such as arterioles (CD34+SMA+), sinusoids (CD34+) and adipocytes is in development.Lastly, Nanostring Fibrosis V2 panel was employed on a subset that met RNA concentration and quality metrics. Exploratory interpretation showed significant differentially expressed genes in pre vs. post JAKi specimens related to lipid metabolism such as ADIPOR1, SCD, ELOVL6 as well as the chemokine CXCL16. This may suggest a link between fatty acid metabolism and inflammatory differentiation along the SMA-vascular axis in the bone marrow modulated by JAKi treatment.SMA-CD34 IHC stratifies MF bone marrow biopsies differentially from standard WHO reticulin/trichome grading providing a practical formalin-fixed paraffin embedded (FFPE) tissue-based biomarker for assessing fibrosis related bone marrow niche elements from archived clinical samples. While our pilot numbers precluded statistical evaluation by JAKi-type, clinical response and NGS mutational profile at this time, further studies are underway to validate the SMA-CD34 signature on a larger MF cohort. [Display omitted] DisclosuresGupta: Sierra Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS-Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Incyte: Honoraria, Research Funding; Constellation Pharma: Consultancy, Honoraria; Pfizer: Consultancy.

Clinical Outcomes at 3 and 6 Months of Fedratinib Therapy Following Prior Ruxolitinib Failure: Real-World Assessment of Spleen, Symptoms, and Hematologic Response

Clinical Outcomes at 3 and 6 Months of Fedratinib Therapy Following Prior Ruxolitinib Failure: Real-World Assessment of Spleen, Symptoms, and Hematologic Response

An Open-Label, Phase II Study Of The JAK1 Inhibitor INCB039110 In Patients With Myelofibrosis

An Open-Label, Phase II Study Of The JAK1 Inhibitor INCB039110 In Patients With Myelofibrosis

Abstract CT236: A Two-Part Phase 2 Study of Itacitinib Immediate Release in Patients with Primary or Secondary Myelofibrosis Who Have Received Prior Ruxolitinib and/or Fedratinib Monotherapy

Abstract Background: Ruxolitinib (JAK1/JAK2 inhibitor) and fedratinib (JAK2/FLT3 inhibitor) are indicated in the US for myelofibrosis (MF); however, some patients fail to achieve adequate/sustained response to initial JAK-inhibitor therapy. Itacitinib is a potent JAK inhibitor selective for JAK1 over JAK2 when administered as a once-daily sustained-release (SR) formulation. In prior clinical trials, the SR formulation improved MF-related symptoms but had less effect with respect to spleen volume reduction. When dosed as a twice-daily (BID) immediate release (IR) formulation, itacitinib may offer increased JAK2 inhibition (in addition to JAK1 inhibition) to better address the JAK2-mediated myeloproliferative features of MF. This open-label phase 2 study is designed to determine a tolerable and safe dose of itacitinib IR that results in clinically significant reductions in symptoms and spleen volume in patients with MF who have previously received ruxolitinib and/or fedratinib monotherapy (INCB 39110-213; NCT04629508). Methods: Eligible patients are aged ≥18 years, diagnosed with at least INT-1 risk (Dynamic International Prognostic Scoring System [Passamonti. Blood. 2010;115:1703-1708]) primary or secondary (post-polycythemia vera or post-essential thrombocythemia) MF and have received ruxolitinib and/or fedratinib monotherapy. Patients must also have palpable splenomegaly and platelets ≥50×109/L at screening. Exclusion criteria include receipt of a JAK inhibitor other than ruxolitinib or fedratinib, ≥10% myeloid blasts in peripheral blood or bone marrow, or inability to taper ruxolitinib/fedratinib over 14 days without use of other agents. Two itacitinib IR dose levels (DLs) will be evaluated in part 1 following a Bayesian optimal interval design algorithm: 3-9 patients will be enrolled at DL1 (300 mg BID) and observed for 28 days for dose-limiting toxicity before enrollment at DL2 (600 mg BID). Part 2 will enroll ~55 patients at the recommended phase 2 dose (RP2D) determined in part 1. Patients may remain on treatment until week 48 if they are receiving clinical benefit and have not met study withdrawal criteria. A safety follow-up will occur 30 days after treatment completion. Primary objectives: part 1 - evaluate safety and tolerability of itacitinib IR and select the RP2D; part 2 - evaluate efficacy of itacitinib IR at the RP2D based on spleen volume reduction at week 24. Secondary objectives (part 2 only): evaluate safety and tolerability of itacitinib IR; evaluate efficacy of itacitinib IR with respect to MF symptom improvement at week 24 in patients with baseline total symptom score ≥10, quality-of-life improvement, and patient global impression of change. Sites are opening in the US and EU. Citation Format: Andrew T. Kuykendall, Lea Burke, Mani Lakshminarayanan, Philomena Colucci. A Two-Part Phase 2 Study of Itacitinib Immediate Release in Patients with Primary or Secondary Myelofibrosis Who Have Received Prior Ruxolitinib and/or Fedratinib Monotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT236.

Primary Analysis of JUMP, a Phase 3b, Expanded-Access Study Evaluating the Safety and Efficacy of Ruxolitinib in Patients with Myelofibrosis (N = 2233)

BACKGROUND: Ruxolitinib is a potent JAK1/JAK2 inhibitor that proved superior to placebo and best available therapy in the phase 3 COMFORT studies in patients (pts) with intermediate (Int)-2- or high-risk myelofibrosis (MF). In these studies, ruxolitinib led to improvements in splenomegaly and MF-related symptoms as well as prolonged overall survival. JUMP is a large, phase 3b, expanded-access trial designed to assess the safety and efficacy of ruxolitinib in pts with MF who do not have access to ruxolitinib outside a clinical trial. Here, we report findings from the primary analysis of JUMP, which includes 2233 pts in 26 countries who received ruxolitinib treatment for ≥ 2 years. METHODS: Eligible pts had Int-2- or high-risk MF, with or without splenomegaly, or Int-1-risk MF with a palpable spleen (≥ 5 cm). The starting dose of ruxolitinib was based on platelet (PLT) counts at baseline (5 mg twice daily [bid; ≥ 50 to 200 × 109/L]) and could be titrated during treatment. The primary endpoint was assessment of safety and tolerability of ruxolitinib. Additional analyses included changes in palpable spleen length and symptom scores. Pts were treated for up to 24 months after the last patient9s first visit (23 December 2014), unless discontinuation criteria were met. RESULTS: This analysis includes 2233 pts (primary MF, 59.4% [n = 1326]). At baseline, median age was 67 y (range, 18-89 y), and 59.7% were aged ≥ 65 y; 54.5% were male; median palpable spleen length was 12 cm below the costal margin; median time since diagnosis was 25.8 months. Median hemoglobin (Hb) was 106 g/L (Hb Median exposure was 12.4 months; the mean average daily dose of ruxolitinib was 28.7 mg. 67.4% of pts had dose modifications, and 27.2% had a dose interruption. The most common grade (G) 3/4 hematologic AEs were anemia (34.8%), thrombocytopenia (16.5%), and neutropenia (4.6%), which led to discontinuation in 1.3%, 2.8%, and 0.1% of pts, respectively. Nonhematologic AEs were primarily G1/2, and the most common (≥ 10%) were pyrexia (16.0%; G3/4, 2.4%), asthenia (15.4%; G3/4, 2.2%), diarrhea (12.5%; G3/4, 1.1%), and fatigue (10.0%; G3/4, 1.0%). Rates of other G3/4 AEs were low (≤ 2%), except pneumonia (4.7%), which led to discontinuation in 10 pts (0.5%). Rates of infections were generally low; all-grade infections in ≥ 5% of pts included pneumonia (7.3%), urinary tract infection (5.9%), herpes zoster (5.2%), and nasopharyngitis (5.2%). Tuberculosis was reported in 5 pts (0.2%; G3/4, At wk 24 and 48, 56.5% (874/1546) and 61.4% (656/1068) of pts with baseline splenomegaly achieved a spleen response (ie, a ≥ 50% reduction from baseline in palpable spleen length); 23.3% (360/1546) and 18.9% (202/1068) had 25% to 50% reductions at wk 24 and 48. Most pts (70.7% [1470/2079]) experienced a ≥ 50% reduction at any time (Figure); the median time to response was 5.8 wk. Pts also experienced substantial improvements in symptoms. A large proportion of pts achieved a response (ie, a clinically significant improvement) on the FACT-Lym TS at wk 24 (53.7% [753/1403]) and wk 48 (53.7% [503/937]). Similar results were seen on the FACIT-Fatigue (wk 24, 49.1% [709/1443]; wk 48, 45.6% [434/952]). CONCLUSIONS: This was the primary analysis of JUMP, the largest study of pts with MF treated with ruxolitinib. Overall, ruxolitinib was effective in pts with MF, leading to reductions in splenomegaly and symptoms in most pts. Consistent with findings from previous studies, anemia and thrombocytopenia were the most common AEs but rarely led to discontinuation. Findings from this analysis, which included pts with Int-1-risk disease, those with low platelet counts (≥ 50 to Disclosures Al-Ali: Novartis: Consultancy, Honoraria, Research Funding; Alexion: Honoraria; Gilead: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Foltz: Pfizer: Consultancy; Incyte: Research Funding; Promedior: Research Funding; Gilead: Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Palumbo: Novartis: Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Amgen: Speakers Bureau; Jannsen: Membership on an entity9s Board of Directors or advisory committees; Teva: Speakers Bureau; Hospira: Membership on an entity9s Board of Directors or advisory committees. Le Coutre: Pfizer: Honoraria; Incyte: Honoraria; BMS: Honoraria; Novartis: Honoraria. Zaritskey: Janssen: Consultancy; Novartis: Consultancy, Speakers Bureau. Tavares: Novartis: Consultancy. Griesshammer: Gilead: Consultancy, Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Baxalta: Consultancy, Honoraria, Speakers Bureau; AOP Orphan: Consultancy, Honoraria, Speakers Bureau; Shire: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau. Gupta: Novartis: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Research Funding. Bouard: Novartis Pharma AG: Employment. Perez Ronco: Novartis Pharma AG: Employment. Tiwari: Novartis Healthcare Pvt Ltd: Employment. Vannucchi: Novartis: Honoraria, Speakers Bureau; Shire: Speakers Bureau.

Adore: A Randomized, Open-Label, Phase 1/2 Open-Platform Study Evaluating Safety and Efficacy of Novel Ruxolitinib Combinations in Patients with Myelofibrosis

Adore: A Randomized, Open-Label, Phase 1/2 Open-Platform Study Evaluating Safety and Efficacy of Novel Ruxolitinib Combinations in Patients with Myelofibrosis

A Phase 3, Open-Label, Randomized Study Evaluating the Efficacy and Safety of Navitoclax Plus Ruxolitinib Versus Best Available Therapy in Patients with Relapsed/Refractory Myelofibrosis (TRANSFORM-2)

Background: Myelofibrosis (MF) is a rare myeloproliferative neoplasm with limited treatment options and a poor prognosis. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers a potential cure, most patients remain ineligible; other therapies, including approved JAK inhibitors (JAKi), do not control the broad array of manifestations associated with MF. Navitoclax is a potent, small molecule inhibitor of the antiapoptotic B-cell lymphoma 2 (BCL-2) family members BCL-XL, BCL-2, and BCL-w and has been shown to potently enhance cytotoxicity of chemotherapy and radiation in cells derived from multiple tumor types. Preclinical data indicate that navitoclax may overcome JAK2 inhibitor resistance. Preliminary data from a Phase 2 study (NCT03222609) of navitoclax with ruxolitinib, a JAK1/2i, for patients with primary or secondary MF who have previously received ruxolitinib suggest favorable spleen response rates and an acceptable safety profile (Harrison et al. EHA 2020. EP1081). TRANSFORM-2 aims to evaluate the combination of navitoclax and ruxolitinib vs best available therapy (BAT) in adults with relapsed or refractory MF that is resistant to JAK2 inhibition. Study Design and Methods: This Phase 3, open-label study (NCT04468984) is designed to recruit patients aged ≥18 years with intermediate-2 or high-risk MF, measurable splenomegaly, and who are experiencing MF-related symptoms. Patients must have received a single prior JAK2i for ≥24 weeks that was stopped due to lack of efficacy or for &amp;lt;24 weeks with disease progression while on therapy. Candidates for allo-HSCT, patients who have received prior treatment with a BH3-mimetic compound or &amp;gt;1 prior JAK2i, and patients with platelets &amp;lt;100 × 109/L will be excluded. The study will be conducted at approximately 173 sites in 23 countries. The planned sample size is 330 patients. Patients will be randomized 1:1 to receive either navitoclax plus ruxolitinib, or BAT. Navitoclax will be administered orally at a starting dose of 200 mg (platelet count &amp;gt;150 × 109/L) or 100 mg escalated to 200 mg once daily if tolerated after ≥7 days (platelet count ≤150 × 109/L); navitoclax may be increased to 300 mg once daily after Week 25 Day 1 at the investigator's discretion, based on platelet count for patients with suboptimal spleen response; ruxolitinib will be administered orally at the prior stable dose if on ruxolitinib at study entry or at a dose of 10 mg twice daily if no longer on ruxolitinib. BAT options include hydroxyurea, interferon, ruxolitinib, fedratinib, or danazol, which will be administered at standard doses. Randomization stratification will be by region (US vs Japan vs EU vs rest of world), by Dynamic International Prognostic Scoring System Plus score at randomization (intermediate-2 vs high risk), and by stable ruxolitinib dosing at randomization vs not on ruxolitinib/JAK2i. Treatment can continue until the end of clinical benefit, unacceptable toxicity, or discontinuation criteria have been met; disease assessments will be performed after 12 and 24 weeks even if discontinuing therapy, after which patients will enter posttreatment follow-up (discontinuation without progression) or survival follow-up (after progression). The primary endpoint is ≥35% reduction in spleen volume from baseline (SVR35) at Week 24, measured by magnetic resonance imaging, per International Working Group criteria. Secondary endpoints include ≥50% reduction in total symptom score from baseline at Week 24, SVR35, duration of SVR35, change in fatigue from baseline, time to deterioration of physical functioning, anemia response, overall survival, leukemia-free survival, overall response, composite response, and reduction in grade of bone marrow fibrosis from baseline. Safety will be assessed via adverse event (AE) monitoring, physical examinations, vital sign measurements, electrocardiogram variables, and clinical laboratory testing. AEs will be graded per National Cancer Institute Common Terminology Criteria for AEs v5.0. Statistical analysis of the primary endpoint and binary secondary endpoints will be conducted using a stratified Cochran-Mantel-Haenszel test. Time-to-event secondary endpoints will be analyzed using a stratified log-rank test and Kaplan-Meier methodology. Hazard ratios will be estimated using stratified Cox proportional hazards model. Disclosures Dilley: AbbVie Inc.: Current Employment, Other: may hold stock or stock options. Harb:AbbVie: Current Employment, Other: may hold stock or stock options. Jalaluddin:AbbVie: Current Employment, Other: may hold stock or stock options. Hutti:AbbVie Inc.: Current Employment, Other: may hold stock or stock options. Potluri:AbbVie: Current Employment, Other: may hold stock or stock options. OffLabel Disclosure: Navitoclax is an investigational drug for the treatment of myelofibrosis

The Final Analysis of Expand: A Phase 1b, Open-Label, Dose-Finding Study of Ruxolitinib (RUX) in Patients (pts) with Myelofibrosis (MF) and Low Platelet (PLT) Count (50 × 109/L to < 100 × 109/L) at Baseline

The Final Analysis of Expand: A Phase 1b, Open-Label, Dose-Finding Study of Ruxolitinib (RUX) in Patients (pts) with Myelofibrosis (MF) and Low Platelet (PLT) Count (50 × 109/L to < 100 × 109/L) at Baseline