Vonjo (pacritinib) / SOBI - LARVOL DELTA

Prescribing patterns in MDS/MPN syndromes (ASH 2025) - "Additionally, the prescribing patterns of Hydroxyurea, Hypomethylating Agents (HMA)- Azacitidine/Decitabine and JAK inhibitors Ruxolitinib/Cedazuridine/Pacritinib/Momelotinib/Fedratinib were analyzed in these patients. In this real-world analysis, our data demonstrate that over 90% of patients diagnosed with MDS/MPN overlap syndromes do not receive any treatment in routine clinical practice. The most prescribed medication in this cohort of patients with MDS/MPN was hydroxyurea, followed by hypomethylating medications (decitabine and azacitidine). Being untreated was associated with a significant decrement in survival, with untreated patients having up to twice the risk of death than those treated."

Atypical Chronic Myeloid Leukemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Juvenile Myelomonocytic Leukemia • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm

Selinexor alone and in combination with JAK inhibitors suppresses pro-inflammatory cytokine secretion from primary myelofibrosis cells ex vivo (ASH 2025) - P3 | "In combination with ruxolitinib (RUX), SEL has shown rapid, deep, and sustained spleenand symptom responses including disease modifying potential in patients with JAK inhibitor(JAKi)–naïve myelofibrosis (MF), with associated reductions in proinflammatory cytokines(Tantravahi SK, et al...JAKis used in MF therapy, including RUX, momelotinib (MOM), and pacritinib(PAC), have limited impact on cytokine modulation... XPO1 inhibition is a potentially fundamental mechanism that addresses keyinflammatory and pathobiological features of MF. Here we demonstrate that SEL effectivelysuppresses ex vivo NF-κB–regulated pro-inflammatory cytokine production in PBMCs derivedfrom patients with MF, both as a single agent and in combination with JAKi, further validating thepotential of disease modification. The combinatory activity of XPO1 inhibition and JAK/STATinhibitors supports the clinical use of SEL plus RUX in JAKi-naïve MF, which is being evaluated inthe ongoing Phase..."

Combination therapy • IO biomarker • Preclinical • Fibrosis • Immunology • Myelofibrosis • CALR • IL6 • JAK2 • TLR8 • XPO1

Pacritinib in transplant-eligible myelofibrosis: Final analysis of the phase 2 HOVON-134 trial (ASH 2025) - "Prior treatment with ruxolitinib (RUX) was allowed if tapered and discontinued beforeinclusion...Per protocol alloHSCT was done witha matched related donor (MRD) or 10/10 matched unrelated donor (MUD) and a standardized reduced-intensity conditioning protocol: intravenous busulfan 3.2 mg/kg adjusted ideal body weight (days -7 to -6)and 1.6 mg/kg adjusted ideal body weight (day -5), fludarabine 30 mg/m2 (days -7 to -2) and anti-Tlymphocyte globulin 10 mg/kg (days -3 to -1) for MRD and 20 mg/kg (days -3 to -1) for MUD. Prophylaxisfor graft-versus-host disease (GVHD) consisted of mycophenolate mofetil (days 0 to 28) and cyclosporineA (days -3 to 100, followed by tapering)... PAC is a feasible and effective symptomatic treatment in transplant-eligible MF-patients andits pre-transplant use does not limit higher-risk patients in proceeding to their intended alloHSCT. Ours isone of few studies in MF showing outcome of alloHSCT by intent-to-transplant."

P2 data • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • CNS Disorders • Graft versus Host Disease • Hematological Disorders • Immunology • Myelofibrosis • Transplantation • Ventriculomegaly • ACVR1 • CD34 • IRAK1 • JAK2

An independent, multi-center analysis of the post-approval utilization and efficacy of pacritinib and momelotinib in patients with myelofibrosis (ASH 2025) - "Early JAK inhibitors(ruxolitinib (RUX) and fedratinib) result in myelosuppression that often exacerbates disease-relatedanemia and thrombocytopenia. The magnitude ofthese differences warrants further investigation. Overall, this real-world study highlights clinical nuancesin JAK inhibitor selection and emphasizes the opportunity to personalize treatment approach."

Clinical • Myelofibrosis • Thrombocytopenia • CALR

Treatment patterns and outcomes in patients with myelofibrosis treated with pacritinib following a switch from ruxolitinib: The my-PAC study (ASH 2025) - "This real-world study demonstrated the utility of switching to PAC following RUX treatment. Amajority of pts had thrombocytopenia or anemia at the time of PAC initiation with most pts experiencingsymptom relief during PAC treatment, clinically meaningful benefits in spleen size and improvement inPLT and Hb following PAC treatment."

Clinical • Hematological Disorders • Myelofibrosis • Thrombocytopenia • ACVR1 • IRAK1

Real-world treatment duration of ruxolitinib and use of transfusion among 2268 patients with myelofibrosis: An analysis of the Medicare fee-for-service claims database (ASH 2025) - "Most pts were treatment naive (n=1564 [69%]); 659 ( hydroxyurea (HU) prior to RUX.During the baseline period, supportive medication for anemia was received by 277 (12%) pts overall(anemia Dx, n=197 [17%]; transfusion, n=102 [26%]), most commonly erythropoiesis-stimulating agents(n=251 [11%]) or danazol (n=43 [2%])...After RUXdiscontinuation, 25% received another MF treatment; the most common treatments were HU (n=256[11%]), fedratinib (n=186 [8%]), and pacritinib (n=115 [5%]). In this real-world study with long-term follow-up of approximately 4 years, median durationof RUX treatment was 3.1 years... In this real-world study with long-term follow-up of approximately 4 years, median durationof RUX treatment was 3.1 years. On average, pts started RUX early after MF diagnosis (median, 4.5 mo),and approximately one-third remained on RUX treatment at end of study period, regardless of age orbaseline anemia status. Most pts did not require transfusions at baseline."

Claims database • Clinical • HEOR • Medicare • Real-world • Real-world evidence • Reimbursement • US reimbursement • Acute Myelogenous Leukemia • Diabetes • Heart Failure • Hematological Disorders • Hematological Malignancies • Leukemia • Metabolic Disorders • Myelodysplastic Syndrome • Myelofibrosis • Nephrology • Peripheral Arterial Disease • Pulmonary Disease • Renal Disease • Respiratory Diseases

It's not yet time to abandon ruxolitinib in anemic myelofibrosis: Predictive factors of erythroid response to standard anemia-directed therapies combined with ruxolitinib (ASH 2025) - "However, on-target RUX-associated anemia represents a major therapeutic limitation,negatively affecting quality of life, prognosis, and treatment duration.Novel JAK1/2 inhibitors, such as momelotinib and pacritinib, also target ACVR1 and may ameliorateanemia both in RUX-naïve and -exposed pts. However, there is a number of standard anemia-directedtherapies (ADT), including erythropoietin (EPO), danazol, steroids and immunomodulatory agents (e.g.thalidomide), that have been used for a long time to manage anemia in MF...Proactive anemia management with EPO, initiated early before the establishment of TDA, isassociated with better RUX survival and favorable safety profile. These results support a personalizedapproach integrating early prognostic assessment with optimized anemia management strategies, inorder to maximize treatment benefits."

Biomarker • Anemia • Myelofibrosis • ACVR1 • CALR

Targeting HMGA1-driven leukemic transformation in myeloproliferative neoplasms with pacritinib (ASH 2025) - "This transcriptional reprogramming promotesproliferation, blocks differentiation, and accelerates leukemic progression in vivo.We discovered that HMGA1 overexpression confers resistance to ruxolitinib and fedratinib by sustainingE2F/G2-M programs. We identified HMGA1 as a critical driver and potent predictor of MPN-sAML transformation.HMGA1 protein expression, readily detectable by immunohistochemistry (IHC), demonstrated a stepwiseincrease from chronic MPN phases to sAML (P40.78%) in non-blast phase MPN predicted impending leukemic transformation within 12months (47% conversion rate), offering a median lead time of 6 months before overt blast crisis."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • CCNB1 • CD34 • CDK2 • E2F1 • FLT3 • HMGA1 • IRAK1 • JAK2 • KIT • TP53

Real-world treatment patterns and clinical outcomes in patients with myelofibrosis treated with pacritinib (PAC): Results from the my-PAC study (ASH 2025) - "Between Day 180, 82.7% (134/162) of pts experienced a reduction in the number ofsymptoms, with a median 67% (IQR: 50.0-100) reduction in symptom burden. By the end of the study, 85.8% (145/169) of pts were alive, and the survival probability from PAC initiationto Day 180 was 93.5 (95% confidence interval: 88.6-96.3).Spleen size reduction, PLT and Hb response, symptom reduction and survival outcomes were consistentregardless of whether PAC was used as 1L or 2L JAKi therapy.Conclusion In real-world clinical settings, pts with MF treated with PAC, regardless of the line of therapy, experiencedreduction or stabilization in spleen size category, improvement in hematologic parameters, and adiminution of MF symptom burden."

Clinical • Clinical data • HEOR • Real-world • Real-world evidence • Hematological Disorders • Myelofibrosis • Thrombocytopenia • ACVR1 • IRAK1 • JAK2 • TINCR

Treatment-requiring paroxysmal nocturnal hemoglobinuria in association with myeloproliferative neoplasms (MPNs): Clinical correlations and outcomes (ASH 2025) - "Cytogeneticanalysis (n =10) demonstrated an abnormal karyotype in 3 patients (30%), all of which were categorizedas favorable risk.First-line treatment for PNH included complement inhibitors in 9 patients (82%), with eculizumab (n=8), orravulizumab (n=1)...Notably, one patient with PNH clone size of 91.19 % in granulocytes, had ongoing hemolysisdespite dual complement blockade with ravulizumab and danicopan.Treatment for MPN included hydroxyurea (n=5), ruxolitinib (n=4), pacritinib (n=1), and erythropoiesisstimulating agents (n=4)...The current study represents the largest series of patients with treatment-requiring PNH and MPN. Itreveals a predominance of MF patients, particularly among those harboring CALR mutations, andunderlines suboptimal efficacy of complement inhibitor therapy in this patient population."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Hematological Malignancies • Infectious Disease • Myelodysplastic Syndrome • Myelofibrosis • Paroxysmal Nocturnal Hemoglobinuria • Polycythemia Vera • Rare Diseases • Septic Shock • Thrombocytosis • Thrombosis • ASXL1 • CALR • JAK2 • SF3B1 • ZRSR2

The transition from myelodysplastic neoplasm to secondary acute myeloid leukemia is revealed by molecular analysis, while functional drug screening demonstrates novel sensitivity patterns with clinical implication (ASH 2025) - "There are only a limited number of agentsthat are FDA approved for treatment of MDS including BCL2 and IDH inhibitors, hypomethylating agents(HMAs), ESAs, luspatercept and imetelstat...For MDS patients, weidentified the most effective agents with the proportion of sensitive samples noted in parentheses:mitoxantrone (100%), olutasidenib (78%), venetoclax (67%), dinaciclib (67%), trametinib (67%), olaparib(56%), GSK3368715 (56%), pacritinib (44%), lenalidomide (44%), fludarabine (55%), tasquinimod (44%),veliparib (44%). For sAML patients, we identified lenalidomide, olutasidenib, GSK3368715 have high DSSsin all tested samples, while fludarabine, fedratinib, tasquinimod, trametinib, veliparib, mitoxantrone andolaparib have high DSSs in 75% of the AML samples...Cancer Research 2024), and our samples included SF3B1 and U2AF1 mutations.Summary This study of the transition of MDS to sAML highlights molecular changes and reveals new drugsensitivity with agents that could be..."

Biomarker • Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • CD34 • FLT3 • JAK2 • NRAS • PTPN11 • SF3B1 • U2AF1

Prospera (ABNL-MARRO 002): A randomized phase 2 study of pacritinib vs. hydroxyurea in patients with advanced proliferative chronic myelomonocytic leukemia (CMML) (ASH 2025) - P2 | "In the phase 3 DACOTA trial (Itzykson et al., JCO 2022),decitabine modestly delayed leukemic transformation compared to HU but did not improve event-free oroverall survival and was associated with increased early mortality. The primary endpoint is CBR at Week 24, defined by modified IWG MDS/MPNcriteria incorporating hematologic improvement, spleen volume reduction, and symptom response.Secondary endpoints include CBR at any time, duration of response, event-free survival, leukemia-freesurvival, and overall survival.Correlative studies will assess treatment-related changes in clonal dynamics, cytokine signaling, andhematopoietic composition using longitudinal peripheral blood and bone marrow sampling. Single-celltranscriptomic and immunophenotypic profiling will be employed to characterize pacritinib's impact onboth the malignant clone and the surrounding immune microenvironment."

Clinical • Metastases • P2 data • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytopenia • IRAK1

Real-world treatment patterns and outcomes in patients with myelofibrosis who presented with thrombocytopenia and anemia at initiation of pacritinib treatment (ASH 2025) - "Most pts received PAC ast the first JAKinhibitors (55.4%; 62/112) while 44.6% (50/112) received ruxolitinib (n=49) or fedratinib (n=1) prior to PAC.The median follow-up from index was 8.9 months (6.9, 12) and a majority were still on PAC at the end ofthe 180-day observation period (70.5%; 79/112). Pts with MF who have both thrombocytopenia and anemia, treated with PAC in the real-world, experienced reduction or stabilization in spleen size category, along with improvements in MF-related symtpom burder, PLT and Hb. A majority of PAC treated pts experiecned symptom relief withbenefits observed as early as 30 days following treatment initiation. PAC may have clinical utility inaddressing unmet needs of pts with MF who have bicytopenias."

Clinical • HEOR • Real-world • Real-world evidence • Anemia • Hematological Disorders • Myelofibrosis • Thrombocytopenia • ACVR1 • IRAK1 • JAK1

A phase 2 study of canakinumab in patient with myelofibrosis: Results from part 1 (ASH 2025) - "Introduction Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) for which the only approved therapies are JAKinhibitors which improve splenomegaly and disease-related symptoms. Given the encouraging impact onMF symptoms, blood counts and reassuring safety profile, the study was amended to enroll pts on astable dose of a JAK inhibitor (ruxolitinib, fedratinib, momelotinib, or pacritinib) who have the potential tobenefit from additional therapy. Part 2 is currently enrolling at multiple sites and updated clinical andcorrelative data will be presented at the meeting."

Clinical • P2 data • Cardiovascular • Fibrosis • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytopenia • CRP • IL1B

Efficacy of the JAK2/FLT3 inhibitor pacritinib in NPM1 mutated Acute Myeloid Leukemia (ASH 2025) - "Our preliminary data suggest thatcombining pacritinib with venetoclax may improve therapeutic efficacy, supporting further exploration ofthis combination as a targeted strategy for NPM1mut AML. Given that genomic mutations alone do notfully account for differential drug responses, ongoing proteomic analyses aim to uncover mechanisms ofsensitivity and resistance, which may guide future precision therapies."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelofibrosis • BCL2 • DNMT3A • FLT3 • IDH1 • IDH2 • JAK2 • NPM1

Leveraging real-world workshop insights for improving education design: Patient-centered care of myelofibrosis with JAK inhibitors (ASH 2025) - "As a resultof this education, relative improvements were observed in selecting guideline- and expert-concordantanswers to pre/post quesitons on: 1) individualizing front-line therapy with ruxolitinib dosing (30%baseline vs 71% post education; P <.001); 2) optimal use of front-line pacritinib for patients with MF andlow platelet count (20% baseline vs 62% post education; P <.001); 3) sequencing JAKi for second-linetherapy (eg, pacritinib, momelotinib, fedratinib) based on patient characteristics (34% baseline vs 69%post education; P <.001) and, 4) recognizing and effectively managing treatment-related AEs in patientsreceiving JAKi therapies (37% baseline vs 69% post education; P <.001). HCP confidence, knowledge, and competence in personalizing JAKi therapy for patients withMF was improved following participation in this multimodal educational program. This educationalinitiative demonstrated that integrating quantitative and qualitative insights from..."

Clinical • Real-world • Real-world evidence • Hematological Disorders • Myelofibrosis • Thrombocytopenia

RALLY MF: A phase 2 Study of DISC-0974, an anti-hemojuvelin antibody, in patients with myelofibrosis and anemia (ASH 2025) - P1/2 | "A stable dose ofconcomitant hydroxyurea and/or Janus kinase (JAK) inhibitor (ruxolitinib and fedratinib for primarycohorts; momelotinib and pacritinib for exploratory cohort) was allowed. Based on these initial data, the protocol was amended to allowconcomitant momelotinib or pacritinib in all cohorts. Preliminary results, including baselinecharacteristics, PD, and hematologic responses across all cohorts, will be presented."

Clinical • P2 data • Anemia • Hematological Disorders • Immunology • Myelofibrosis

Pacritinib in patients with high-risk myelofibrosis: Outcomes from post-hoc analyses of two Phase 3 studies (ASH 2025) - P3 | "The PAC treatmentarms from PERSIST-1 (400 mg once daily [QD) and PERSIST-2 (400 mg QD and 200 mg twice daily [BID])were pooled, as was the BAT group (including ruxolitinib) from each study. Patients with high-risk MF treated with PAC had significant improvements in spleen size andsymptom burden when compared to BAT. The safety profile reported for this subgroup was similar towhat has already been reported for PAC in the primary analysis. The prolonged survival of PAC-treatedpatients in this high-risk cohort, as well as the overall efficacy and safety of PAC in this group supportsPAC as an important therapeutic option for high-risk MF patients, addressing a critical unmet need in thispopulation with historically poor outcomes."

Clinical • P3 data • Retrospective data • Hematological Disorders • Myelofibrosis • ACVR1 • IRAK1 • JAK1

Ruxolitinib duration of treatment and effect on phlebotomy use among 2369 patients with polycythemia vera: A real-world analysis of the Medicare fee-for-service claims database (ASH 2025) - "Background : Ruxolitinib (RUX) is approved for the treatment of adults with polycythemia vera (PV) haveinadequate response to or are intolerant of hydroxyurea (HU)...Among the 691 patients who received phlebotomy at baseline, 60%(n=415) did not receive any phlebotomy during the first 6 months post-index, and 73% (n=506) did notreceive any phlebotomy during months 7–12 post-index.After RUX discontinuation, the most common treatments among all 2369 patients were HU (17%; n=410)and phlebotomy (14%; n=323), followed by fedratinib (3%, n=66), anagrelide (3%; n=64), pacritinib (2%; n=41), and interferon (n<11). In this large retrospective real-world study with over 4 years of follow-up, older patients withPV continued RUX treatment for a median of 3.6 years, and more than one-third of patients remained onRUX treatment at the end of the study period... In this large retrospective real-world study with over 4 years of follow-up, older patients withPV continued RUX treatment..."

Claims database • Clinical • Medicare • Real-world • Real-world evidence • Reimbursement • US reimbursement • Acute Myelogenous Leukemia • CNS Disorders • Diabetes • Essential Thrombocythemia • Hematological Malignancies • Leukemia • Metabolic Disorders • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Nephrology • Peripheral Arterial Disease • Polycythemia Vera • Pulmonary Disease • Renal Disease • Respiratory Diseases • Vascular Neurology

Ernest Beutler Lecture and Prize (ASH 2025) - "The ensuing years have also shown benefit of ruxolitinib on survival for MF. Subsequently, three additional JAK inhibitors — each with their own incremental benefits — have been approved (fedratinib in 2019, pacritinib in 2022, and momelotinib in 2023). A new generation of more mutant selective JAK2 inhibitors (INCB160058, AJ1-11095) is currently in early clinical trials...Radek C. Skoda will describe how the JAK2-V617F mutation drives hematopoiesis causing MPNs and recent advances in understanding of how this mutation activates the JAK2 kinase, opening new ways to find candidate drugs preferentially targeting the mutated JAK2 protein.Dr. Ruben Mesa will summarize how the single-agent JAK inhibitors significantly helped decrease the burden of MPNs and the role of current agents, the next generation of new inhibitors, and combination approaches, as well as the impact JAK inhibitors have had on non-neoplastic inflammatory disorders."

Atopic Dermatitis • Chronic Graft versus Host Disease • Dermatitis • Dermatology • Essential Thrombocythemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytosis • Vitiligo • CALR • TET2

Janus Kinase Inhibitors During Pregnancy and Adverse Drug Reactions: A Pharmacovigilance Disproportionality Analysis in VigiBase. (PubMed, Clin Transl Sci) - "This study analyzed VigiBase, the World Health Organization global pharmacovigilance database of individual case safety reports (ICSRs), to assess signals of disproportionate reporting (SDRs) for pregnancy-related adverse drug reactions (ADRs) reported with systemic JAKIs, including abrocitinib, baricitinib, deucravacitinib, fedratinib, filgotinib, itacitinib, momelotinib, pacritinib, peficitinib, ritlecitinib, ruxolitinib, tofacitinib, and upadacitinib. Findings should be interpreted cautiously given the limitations of spontaneous reporting systems and the exploratory nature of the analysis. Further studies are needed to better characterize the JAKI safety in pregnancy."

Adverse drug reaction • Adverse events • Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Study to Assess the Effectiveness and Safety of Pacritinib in Patients With VEXAS Syndrome (PAXIS) (clinicaltrials.gov) - P2 | N=78 | Active, not recruiting | Sponsor: Swedish Orphan Biovitrum | Recruiting ➔ Active, not recruiting

Enrollment closed

JAK inhibitor selection in challenging scenarios of myelofibrosis: a review. (PubMed, Haematologica) - "A total of four JAK inhibitors-ruxolitinib, fedratinib, pacritinib, and momelotinib-are now available for the treatment of myelofibrosis, each with distinct profiles and safety considerations that may inform selection. To illustrate the diverse clinical factors and key considerations associated with JAK inhibitor selection in practice, we discuss these data in the context of four hypothetical patient cases representing possible real-world scenarios, offering treatment recommendations based on our collective expertise in the field. As the myelofibrosis therapeutic landscape continues to evolve, a thorough understanding of the strengths and limitations of each JAK inhibitor relative to a given patient's presentation will support individualized treatment decisions for optimal long-term outcomes."

Journal • Bone Marrow Transplantation • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Transplantation

Sobi to Showcase Scientific advances and Commitment to Haematology at ASH 2025 (PRNewswire) - "Sobi's innovative portfolio including data from efanesoctocog alfa, pegcetacoplan, avatrombopag, emapalumab, and pacritinib....Overview of treatment advances with complement Inhibitors in patients with Paroxysmal Nocturnal Haemoglobinuria; Optimising PNH treatment with the complement inhibitor Pegcetacoplan: A case report; User experience with Pegcetacoplan on-body Injector in patients with Paroxysmal Nocturnal Hemoglobinuria."

Clinical data • Aplastic Anemia • Chronic Myelomonocytic Leukemia • Hemophagocytic lymphohistiocytosis • Hemophilia A • Immune Thrombocytopenic Purpura • Myelofibrosis • Paroxysmal Nocturnal Hemoglobinuria

Pacritinib Blocks Key Pro-Survival Signaling Related to Mutated MYD88, Produces High Levels of Apoptosis and Overcomes Mutated BTKCys481 Related BTK-Inhibitor Resistance (ASH 2023) - " We performed comparative studies to evaluate the activity of pacritinib and the covalent BTK-inhibitors ibrutinib and zanubrutinib on mutated MYD88 relevant pro-survival signaling, as well as proliferation and survival in MYD88 mutated cell lines and primary MYD88-mutated WM cells...Lastly, pacritinib alone and combined with venetoclax induced high levels of apoptosis in BTKCys481Ser expressing covalent BTK-inhibitor resistant MYD88 mutated WM and ABC DLBCL lymphoma cells... Pacritinib more broadly extinguishes mutated MYD88 pro-survival signaling cascades (Fig 1.) and demonstrates high levels of apoptotic activity in mutated MYD88 WM and ABC DLBCL cells versus selective covalent BTK-inhibitors. Pacritinib also synergizes with covalent BTK- and BCL2 inhibitors and can overcome covalent BTK-inhibitor resistance related to mutated BTKCys481. Our studies provide a framework for investigating pacritinib in MYD88 mutated lymphomas."

IO biomarker • Chronic Lymphocytic Leukemia • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Myelofibrosis • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Waldenstrom Macroglobulinemia • IL6R • IRAK4 • MYD88 • SYK