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Myelofibrosis (MF) has heterogeneous clinical manifestations, with some patients exhibiting a myelodepletive phenotype characterized by cytopenias and an absent or low JAK2V617F allele burden. Ruxolitinib may be less effective in these patients. We assessed the efficacy of pacritinib, a JAK2/IRAK1 inhibitor, in MF patients with low JAK2V617F allele burden. In this post hoc analysis of the PERSIST-1 and -2 trials, patients with MF randomized to pacritinib or best available therapy (BAT) were stratified by JAK2V617F allele burden quartile for spleen response of ≥35% and improvement in total symptom score of ≥50%. Five hundred thirty-six patients were included. Patients with lower JAK2V617F allele burden had smaller baseline spleens and lower hemoglobin and platelet counts as compared with higher allele burden patients. Among pacritinib-treated patients, spleen responses were observed across all JAK2V617F allele burden quartiles and in JAK2V617F− disease. No spleen responses were observed among BAT-treated patients with allele burden ≤50% or JAK2V617F− disease. The intention-to-treat response rate was significantly higher on the pacritinib arm for JAK2V617F− disease (23.0% vs 0%; P = .033), and for the lowest allele burden quartiles (0%-25%: 20.9% vs 0%, P < .001; 25%-50%: 15.4% vs 0%, P = .020). There were significantly more symptom responders with pacritinib vs BAT in the 0% to 25% and 25% to 50% cohorts. Pacritinib treatment led to superior spleen and symptom burden reduction compared with BAT in patients with absent or low JAK2V617F allele burden, suggesting that pacritinib may be uniquely suited for patients with myelodepletive MF.

Myelofibrosis (MF) has heterogeneous clinical manifestations, with some patients exhibiting a myelodepletive phenotype characterized by cytopenias and an absent or low JAK2V617Fallele burden. Ruxolitinib may be less effective in these patients. We assessed the efficacy of pacritinib, a JAK2/IRAK1 inhibitor, in MF patients with low JAK2V617Fallele burden. In this post hoc analysis of the PERSIST-1 and -2 trials, patients with MF randomized to pacritinib or best available therapy (BAT) were stratified by JAK2V617Fallele burden quartile for spleen response of ≥35% and improvement in total symptom score of ≥50%. Five hundred thirty-six patients were included. Patients with lower JAK2V617Fallele burden had smaller baseline spleens and lower hemoglobin and platelet counts as compared with higher allele burden patients. Among pacritinib-treated patients, spleen responses were observed across all JAK2V617Fallele burden quartiles and in JAK2V617F−disease. No spleen responses were observed among BAT-treated patients with allele burden ≤50% or JAK2V617F−disease. The intention-to-treat response rate was significantly higher on the pacritinib arm for JAK2V617F−disease (23.0% vs 0%; P= .033), and for the lowest allele burden quartiles (0%-25%: 20.9% vs 0%, P< .001; 25%-50%: 15.4% vs 0%, P= .020). There were significantly more symptom responders with pacritinib vs BAT in the 0% to 25% and 25% to 50% cohorts. Pacritinib treatment led to superior spleen and symptom burden reduction compared with BAT in patients with absent or low JAK2V617Fallele burden, suggesting that pacritinib may be uniquely suited for patients with myelodepletive MF.

PAC203 is a randomized dose-finding study of pacritinib, an oral JAK2/IRAK1 inhibitor, in patients with advanced myelofibrosis who are intolerant of or resistant to ruxolitinib. Patients were randomized 1:1:1 to pacritinib 100 mg once per day, 100 mg twice per day, or 200 mg twice per day. Enhanced eligibility criteria, monitoring, and dose modifications were implemented to mitigate risk of cardiac and hemorrhagic events. Efficacy was based on ≥35% spleen volume response (SVR) and ≥50% reduction in the 7-component total symptom score (TSS) through week 24. Of 161 patients, 73% were intolerant of and 76% had become resistant to ruxolitinib; 50% met criteria for both. Severe thrombocytopenia (platelet count <50 × 103/μL) was present in 44%. SVR rates were highest with 200 mg twice per day (100 mg once per day, 0%; 100 mg twice per day, 1.8%; 200 mg twice per day, 9.3%), particularly among patients with baseline platelet counts <50 × 103/μL (17%; 4 of 24). Although TSS response rate was similar across doses (100 mg once per day, 7.7%; 100 mg twice per day, 7.3%; 200 mg twice per day, 7.4%), median percent reduction in TSS suggested a dose-response relationship (–3%, −16%, and −27%, respectively). Pharmacokinetic and pharmacodynamic modeling based on all available data showed greatest SVR and TSS reduction at 200 mg twice per day compared with lower doses. Common adverse events were gastrointestinal events, thrombocytopenia, and anemia. There was no excess of grade ≥3 hemorrhagic or cardiac events at 200 mg twice per day. Pacritinib 200 mg twice per day demonstrated clinical activity and an acceptable safety profile and was selected as the recommended dose for a pivotal phase 3 study in patients with myelofibrosis and severe thrombocytopenia. This trial was registered at www.clinicaltrials.gov as #NCT03165734.

PAC203 is a randomized dose-finding study of pacritinib, an oral JAK2/IRAK1 inhibitor, in patients with advanced myelofibrosis who are intolerant of or resistant to ruxolitinib. Patients were randomized 1:1:1 to pacritinib 100 mg once per day, 100 mg twice per day, or 200 mg twice per day. Enhanced eligibility criteria, monitoring, and dose modifications were implemented to mitigate risk of cardiac and hemorrhagic events. Efficacy was based on ≥35% spleen volume response (SVR) and ≥50% reduction in the 7-component total symptom score (TSS) through week 24. Of 161 patients, 73% were intolerant of and 76% had become resistant to ruxolitinib; 50% met criteria for both. Severe thrombocytopenia (platelet count <50 × 103/μL) was present in 44%. SVR rates were highest with 200 mg twice per day (100 mg once per day, 0%; 100 mg twice per day, 1.8%; 200 mg twice per day, 9.3%), particularly among patients with baseline platelet counts <50 × 103/μL (17%; 4 of 24). Although TSS response rate was similar across doses (100 mg once per day, 7.7%; 100 mg twice per day, 7.3%; 200 mg twice per day, 7.4%), median percent reduction in TSS suggested a dose-response relationship (–3%, −16%, and −27%, respectively). Pharmacokinetic and pharmacodynamic modeling based on all available data showed greatest SVR and TSS reduction at 200 mg twice per day compared with lower doses. Common adverse events were gastrointestinal events, thrombocytopenia, and anemia. There was no excess of grade ≥3 hemorrhagic or cardiac events at 200 mg twice per day. Pacritinib 200 mg twice per day demonstrated clinical activity and an acceptable safety profile and was selected as the recommended dose for a pivotal phase 3 study in patients with myelofibrosis and severe thrombocytopenia. This trial was registered at www.clinicaltrials.govas #NCT03165734.

Background:Myelofibrosis (MF) is a myeloid malignancy characterized by clonal hematopoisis, bone marrow fibrosis (BMF) and ineffective extramedullary hematopoiesis, resulting in progressive cytopenias. Thrombocytopenia is both prognostic of poor outcomes and predictive of treatment intolerance with the JAK1/2 inhibitor ruxolitinib, which exacerbates cytopenias. Pacritinib is a JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1 that can be administered at full dose to patients regardless of baseline platelet count (PLT). While prior studies have shown that pacritinib is associated with PLT stability in most patients, PLT improvement has not been described outside of a recently published case report ( Yacoub A, et al. JCO Precis Oncol. 2023;7:e2200523). Here, we report rates of hematologic improvement in PLTs (HI-P) with pacritinib across two clinical trials.

BackgroundPacritinib is a JAK1-sparing JAK2/IRAK1/ACVR1 inhibitor for treatment of myelofibrosis (MF). In addition to improving spleen volume and symptoms, pacritinib is associated with anemia benefit in MF patients. Recent in vivostudies have shown that dual JAK2/IRAK1 inhibition is associated with improvement in both cytopenias and bone marrow reticulin fibrosis (BMF) in an inflammation-driven murine MF model ( Cuenca Zamora E, et al. EHA 2023; P987 and P990). Here, we retrospectively analyzed the relationship between achieving transfusion independence and reduction in BMF in MF patients treated with pacritinib 200 mg twice daily (BID) vs ruxolitinib (RUX) on the phase 3 PERSIST-2 study.

Background:Pacritinib is a JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1 that demonstrated symptom benefit measured by TSS (v2.0, excluding tiredness) vs best available therapy (BAT) in PERSIST-2, which enrolled cytopenic myelofibrosis patients with platelets ≤100×10 9/L. Recent datashowed that in patients with cytopenic MF, a ≥10% reduction in spleen volume at 12 weeks is associated with improved survival in patients treated with pacritinib ( Ajufo H, et al., J Clin Oncol;2023:14(16):Suppl). Surprisingly, this association was not confirmed in patients treated with BAT (82% of whom were on ruxolitinib). The association between other important measures of clinical benefit such as symptom burden reduction and anemia improvement on survival in patients treated with pacritinib has not previously been described.

•Pacritinib exhibits fourfold higher potency for inhibition of the hepcidin regulator ACVR1 compared to momelotinib based on in vitro data.•Pacritinib is associated with an increase in red blood cell transfusion independence in patients with cytopenic myelofibrosis.

Introduction:Thrombocytopenia, a hallmark of cytopenic myelofibrosis (MF), is associated with poor survival and quality of life impairment. Patients with MF and moderate or severe thrombocytopenia (platelet counts <100x10 9/L, <50x10 9/L) tend to have high symptom burden as measured by the Total Symptom Score (TSS), driven largely by physical functioning symptoms (Mesa R et al, ASH 2021 abstract in submission). Pacritinib, an investigational JAK2/IRAK1 inhibitor, was studied in patients with platelet counts ≤100x10 9/L in the PERSIST-2 trial. Unlike the pivotal studies upon which available JAK1/2 inhibitors were approved that relied on a modifiedTSS version that excluded ‘tiredness’ from the response analysis, PERSIST-2 included ‘tiredness’ as part of TSS and found response rates of 25% for pacritinib vs. 14% for best available therapy (BAT), P=0.08. Here, we retrospectively analyzed TSS on PERSIST-2 using the modifiedscoring system. In addition, we evaluated the impact of pacritinib and BAT, including ruxolitinib, on MF symptoms including ‘tiredness’ and ‘inactivity’.

Introduction:Pacritinib is a JAK2/IRAK1 inhibitor in development for patients with myelofibrosis who have thrombocytopenia. While lower doses of the approved JAK1/2 inhibitor ruxolitinib have been commonly used for the treatment of patients with thrombocytopenia, there is no dosing guidance in the package insert for patients with platelet counts (PLTs) <50 x10 9/L. The starting dose of ruxolitinib in patients with PLTs 50-100 x10 9/L is markedly reduced, which may limit efficacy. Pacritinib, in contrast, was studied without dose attenuation in thrombocytopenic patients (PLTs ≤100 x10 9/L) in the randomized Phase 3 PERSIST-2 study, which showed superior efficacy for pacritinib compared to best available therapy (BAT) based on spleen volume reduction (SVR) and modified total symptom score (TSS) response [Palmer J et al. In submission: ASH abstract 2021]. While many patients in the BAT arm (45%) received ruxolitinib, a comparison between pacritinib and ruxolitinib has not been performed. Here, we conducted a retrospective head-to-head comparison of pacritinib versus ruxolitinib in “first line” (ruxolitinib-naïve) patients treated on PERSIST-2.

Mascarenhas: Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Geron: Consultancy, Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Promedior: Consultancy, Membership on an entity's Board of Directors or advisory committees; Prelude: Consultancy; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy; Merus: Research Funding; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Galecto: Consultancy; Kartos: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Constellation: Consultancy, Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forbius: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CTI Biopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Bose: BMS: Honoraria, Research Funding; NS Pharma: Research Funding; Celgene Corporation: Honoraria, Research Funding; CTI BioPharma: Honoraria, Research Funding; Astellas: Research Funding; Pfizer: Research Funding; Constellation Pharmaceuticals: Research Funding; Incyte Corporation: Honoraria, Research Funding; Sierra Oncology: Honoraria; Kartos Therapeutics: Honoraria, Research Funding; Novartis: Honoraria; Blueprint Medicines: Honoraria, Research Funding; Promedior: Research Funding. Kiladjian: Taiho Oncology, Inc.: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Other: Personal fees; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; AOP Orphan: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees. Mesa: CTI: Research Funding; Abbvie: Research Funding; Novartis: Consultancy; Incyte Corporation: Consultancy, Research Funding; Pharma: Consultancy; Constellation Pharmaceuticals: Consultancy, Research Funding; Genentech: Research Funding; Sierra Oncology: Consultancy, Research Funding; AOP: Consultancy; Gilead: Research Funding; Promedior: Research Funding; Samus: Research Funding; CTI: Research Funding; La Jolla Pharma: Consultancy; Celgene: Research Funding. Gerds: Novartis: Consultancy; PharmaEssentia Corporation: Consultancy; Constellation: Consultancy; CTI BioPharma: Research Funding; Sierra Oncology: Consultancy; AbbVie: Consultancy; Celgene/Bristol Myers Squibb: Consultancy. Gupta: BMS-Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Constellation Pharma: Consultancy, Honoraria; Incyte: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sierra Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy. Harrison: Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Constellation Pharmaceuticals: Research Funding; Incyte Corporation: Speakers Bureau; Geron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Keros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Promedior: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sierra Oncology: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Galacteo: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AOP Orphan Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Yacoub: Agios: Membership on an entity's Board of Directors or advisory committees; Acceleron Pharma: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau. Garcia Gutierrez: Novartis: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Vannucchi: Incyte Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Scheid: Roche: Consultancy; Abbvie: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Buckley: CTI Biopharm: Current Employment. Roman-Torres: CTI Biopharm: Current Employment. Oh: Abbvie: Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Membership on an entity's Board of Directors or advisory committees; Celgene Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Constellation: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Disc Medicine: Membership on an entity's Board of Directors or advisory committees; Geron: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Kartos Therapeutics: Membership on an entity's Board of Directors or advisory committees; PharamaEssentia: Membership on an entity's Board of Directors or advisory committees; Sierra Oncology: Membership on an entity's Board of Directors or advisory committees. Sobas: Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Verstovsek: CTI BioPharma: Research Funding; Celgene: Consultancy, Research Funding; Genentech: Research Funding; Gilead: Research Funding; Promedior: Research Funding; Protagonist Therapeutics: Research Funding; Ital Pharma: Research Funding; Incyte Corporation: Consultancy, Research Funding; NS Pharma: Research Funding; Blueprint Medicines Corp: Research Funding; PharmaEssentia: Research Funding; Roche: Research Funding; AstraZeneca: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; Constellation: Consultancy; Pragmatist: Consultancy.

Mascarenhas: Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kartos: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merus: Research Funding; Geron: Consultancy, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Constellation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prelude: Consultancy; Geron: Consultancy; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Galecto: Consultancy; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CTI Biopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forbius: Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Promedior: Consultancy, Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Harrison: Constellation Pharmaceuticals: Research Funding; Sierra Oncology: Honoraria; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AOP Orphan Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Promedior: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Galacteo: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Keros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Geron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte Corporation: Speakers Bureau. Gerds: Constellation: Consultancy; Celgene/Bristol Myers Squibb: Consultancy; AbbVie: Consultancy; Sierra Oncology: Consultancy; CTI BioPharma: Research Funding; PharmaEssentia Corporation: Consultancy; Novartis: Consultancy. Rampal: Incyte: Consultancy, Research Funding; BMS/Celgene: Consultancy; Stemline: Consultancy, Research Funding; Kartos: Consultancy; Constellation: Research Funding; Jazz Pharmaceuticals: Consultancy; Blueprint: Consultancy; CTI: Consultancy; Abbvie: Consultancy; Novartis: Consultancy; Pharmaessentia: Consultancy; Sierra Oncology: Consultancy; Memorial Sloan Kettering: Current Employment; Disc Medicine: Consultancy. Buckley: CTI Biopharm: Current Employment. Craig: CTI BioPharma: Current Employment. Smith: CTI: Current Employment. Volpone: CTI: Current Employment. Roman-Torres: CTI Biopharm: Current Employment. Mesa: Samus: Research Funding; Constellation Pharmaceuticals: Consultancy, Research Funding; Incyte Corporation: Consultancy, Research Funding; Pharma: Consultancy; CTI: Research Funding; CTI: Research Funding; Sierra Oncology: Consultancy, Research Funding; Abbvie: Research Funding; Promedior: Research Funding; AOP: Consultancy; La Jolla Pharma: Consultancy; Genentech: Research Funding; Novartis: Consultancy; Gilead: Research Funding; Celgene: Research Funding.

Palmer: CTI BioPharma: Consultancy, Research Funding; Protagonist: Consultancy, Research Funding; Incyte: Research Funding; PharmaEssentia: Research Funding; Sierra Oncology: Consultancy, Research Funding. Mesa: Incyte Corporation: Consultancy, Research Funding; Samus: Research Funding; Sierra Oncology: Consultancy, Research Funding; CTI: Research Funding; Novartis: Consultancy; Celgene: Research Funding; Pharma: Consultancy; La Jolla Pharma: Consultancy; Constellation Pharmaceuticals: Consultancy, Research Funding; CTI: Research Funding; Abbvie: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Promedior: Research Funding; AOP: Consultancy. Oh: Abbvie: Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Membership on an entity's Board of Directors or advisory committees; Celgene Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Constellation: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Disc Medicine: Membership on an entity's Board of Directors or advisory committees; Geron: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Kartos Therapeutics: Membership on an entity's Board of Directors or advisory committees; PharamaEssentia: Membership on an entity's Board of Directors or advisory committees; Sierra Oncology: Membership on an entity's Board of Directors or advisory committees. Rampal: Sierra Oncology: Consultancy; Novartis: Consultancy; BMS/Celgene: Consultancy; Stemline: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Constellation: Research Funding; Kartos: Consultancy; Disc Medicine: Consultancy; Blueprint: Consultancy; Pharmaessentia: Consultancy; Incyte: Consultancy, Research Funding; Memorial Sloan Kettering: Current Employment; Abbvie: Consultancy; CTI: Consultancy. Buckley: CTI Biopharm: Current Employment. Roman-Torres: CTI Biopharm: Current Employment. Verstovsek: Protagonist Therapeutics: Research Funding; Genentech: Research Funding; Gilead: Research Funding; Incyte Corporation: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; NS Pharma: Research Funding; AstraZeneca: Research Funding; Blueprint Medicines Corp: Research Funding; CTI BioPharma: Research Funding; Promedior: Research Funding; Ital Pharma: Research Funding; PharmaEssentia: Research Funding; Roche: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; Constellation: Consultancy; Pragmatist: Consultancy. Mascarenhas: Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merus: Research Funding; Geron: Consultancy; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forbius: Research Funding; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Geron: Consultancy, Research Funding; Constellation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Promedior: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kartos: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prelude: Consultancy; Galecto: Consultancy; CTI Biopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Vannucchi: AbbVie: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kiladjian: CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; AP Orphan: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Membership on an entity's Board of Directors or advisory committees. Harrison: Galacteo: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Promedior: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Constellation Pharmaceuticals: Research Funding; Incyte Corporation: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Keros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AOP Orphan Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sierra Oncology: Honoraria; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Geron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Bose: Novartis: Honoraria; NS Pharma: Research Funding; Pfizer: Research Funding; Constellation Pharmaceuticals: Research Funding; Blueprint Medicines: Honoraria, Research Funding; Kartos Therapeutics: Honoraria, Research Funding; Incyte Corporation: Honoraria, Research Funding; Promedior: Research Funding; CTI BioPharma: Honoraria, Research Funding; Sierra Oncology: Honoraria; Astellas: Research Funding; BMS: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding. Craig: CTI BioPharma: Current Employment. Gerds: PharmaEssentia Corporation: Consultancy; CTI BioPharma: Research Funding; Sierra Oncology: Consultancy; AbbVie: Consultancy; Celgene/Bristol Myers Squibb: Consultancy; Constellation: Consultancy; Novartis: Consultancy.

Introduction: Severe thrombocytopenia (platelet count <50,000/μL) in myelofibrosis (MF) patients is a well-established prognostic factor associated with greater symptom burden and poor survival. In 2 large (>1000 patient) retrospective analyses, MF patients with severe thrombocytopenia had a median survival of 15 months, compared to 34-44 months for those with a platelet count 50,000-100,000/μL and 47-89 months with a platelet count >100,000/μL (Masarova L, et al.EJH 2018;100:257-263; Alhuraiji A, et al.JCO 2016;34:7068). Options for patients with severe thrombocytopenia are limited, and clinical trials often exclude them due to risk of treatment-related cytopenias. Pacritinib (PAC) is an oral JAK2/IRAK1 inhibitor that was evaluated for spleen volume reduction (SVR) and total symptom score (TSS) in two phase 3 studies (PERSIST-1 [P1] and PERSIST-2 [P2]) in MF patients, including those with severe thrombocytopenia. P1 studied JAK inhibitor naive patients with no lower platelet limitation, and P2 was limited to patients with a platelet count <100,000/μL, with or without prior JAK inhibitors (eg, ruxolitinib). To better evaluate PAC in MF patients with baseline platelet count <50,000/μL, a retrospective pooled analysis was performed on data from P1/P2. Clinical trial outcomes from this high-risk MF population have not previously been reported.

Mesa: Novartis: Consultancy; Samus: Research Funding; Celgene: Research Funding; Promedior: Research Funding; Incyte: Research Funding; AbbVie: Research Funding; Genotech: Research Funding; La Jolla Pharma: Consultancy; CTI Biopharma: Research Funding; Sierra Onc: Consultancy. Talpaz:Novartis: Research Funding; Incyte: Research Funding; Constellation: Research Funding; CTI BioPharma: Research Funding; Celgene: Consultancy, Research Funding; Imago BioSciences: Consultancy, Research Funding; Samus Therapeutics: Research Funding. Kiladjian:Novartis: Honoraria, Research Funding; Celgene: Consultancy; AOP Orphan: Honoraria, Research Funding. Harrison:Janssen: Speakers Bureau; CTI: Speakers Bureau; Roche: Honoraria; Promedior: Honoraria; Gilead: Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Incyte: Speakers Bureau; Sierra Oncology: Honoraria; Shire: Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; AOP: Honoraria. Verstovsek:Promedior: Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Incyte: Research Funding; CTI BioPharma Corp: Research Funding; Genetech: Research Funding; Blueprint Medicines Corp: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Research Funding; Pharma Essentia: Research Funding; Astrazeneca: Research Funding; Ital Pharma: Research Funding; Protaganist Therapeutics: Research Funding; Constellation: Consultancy; Pragmatist: Consultancy; Gilead: Research Funding; Celgene: Consultancy, Research Funding. Buckley:CTI BioPharma: Employment, Equity Ownership. Roman-Torres:CTI BioPharma: Other: Contractor. Mascarenhas:Janssen: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Roche: Consultancy, Research Funding; Merck: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Promedior: Research Funding; Merus: Research Funding; Pharmaessentia: Consultancy, Membership on an entity's Board of Directors or advisory committees.