November 10, 2023

Saskia Klein (UMCG, Netherlands) Gerwin Huls (University Medical Center Groningen, Netherlands), Otto Visser (IKNL, Netherlands) Hanneke Kluin-Nelemans (University Medical Center Groningen, University og Groningen, Netherlands) Avinash Dinmohamed (Erasmus MC AND Amsterdam UMC, Netherlands)

Abstract
MDS/ MPN with neutrophilia, until recently called atypical chronic myeloid leukemia (aCML), being part of the myelodysplastic/myeloproliferative neoplasms is a very rare disease with poor prognosis. Although emerging data reveal its cytogenetic and molecular profile, integrated survival and treatment data remain scarce. We analyzed a cohort of 347 adult patients diagnosed with MDS/
MPN with neutrophilia, registered in the Netherlands Cancer Registry between 2001 and 2019. Our demographic baseline data align with other cohorts. We observed cytogenetic aberrations exclusively in patients aged >65 years, with trisomy 8 being the most common abnormality. We identified 16 distinct molecular mutations, with some patients (16/101) harboring up to 3 different mutations; ASXL1 being the most frequent one (22%). In a multivariable Cox regression analysis, only age, hemoglobin level and allogeneic hematopoietic stem cell transplant (alloHSCT) were associated with overall survival (>65 years of age HR 1.85, P=0.001 and alloHSCT HR 0.51, P=0.039). As no other treatment modality, seemed to impact survival and might cause toxicity, we propose that all patients eligible for alloHSCT should whenever possible receive an allogeneic transplant. It is imperative that we strive to improve outcomes for patients not eligible for alloHSCT. Tackling this challenge requires international collaborative efforts to conduct prospective intervention studies.

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November 8, 2023

Johnathan Goodman, MPHiL

Patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs) are at an increased risk of arterial and venous thromboembolic (ATE and VTE, respectively) complications, according to research published in Hamostaseologie. Patients with polycythemia vera (PV), furthermore, appeared to be at a particularly high risk for these events.
BCR-ABL-negative MPNs, which include PV, essential thrombocythemia (ET), and myelofibrosis (MF), are each associated with an increased risk of VTE and ATE. These events, moreover, are linked with an increased risk of both morbidity and mortality.

Previous research has suggested that JAK2 mutations are linked with an increased risk of thromboembolic events, while CALR mutations in the MF setting may reduce this risk. Detailed data in these populations are lacking, necessitating further study for risk stratification.

Overall, in the enrolled cohort, 39.1% of patients were male, the median age at MPN diagnosis was 50.7 years, and 31.7%, 34.1%, and 31.1% of patients had ET, PV, and MF, respectively; 3% of patients had an unclassified MPN. Genetic analysis showed that 69.8% of patients had a JAK2 mutation, while 14.4% of patients had a CALR mutation.

The median follow-up was 6.6 years, during which 180 first thromboembolic events were noted; 105 and 75 events were VTEs and ATEs, respectively. The incidence rate for first ATE or VTE was 2.43% per patient/year; the overall probability of a vascular event was 36.2%.

The most commonly noted VTE subtype was deep vein thrombosis (incidence rate, 0.59% per patient/year); the most common ATE subtype was stroke (incidence rate, 0.32% per patient/year).

Analysis showed that PV was linked with a higher risk of ATE or VTE (hazard ratio [HR], 1.66; 95% CI, 1.206-2.286). Compared with JAK2 mutations, CALR mutations were linked with a lower risk of these events (HR, 0.346; 95% CI, 0.172-0.699).

“While patients diagnosed with PV or generally JAK2 mutated MPN patients had a significantly increased risk of thromboembolic complications compared with the other MPN subtypes, this risk was significantly reduced in CALR-mutated patients,” the authors wrote in their report.

Reference

Wille K, Deventer E, Sadjadian P, et al. Arterial and venous thromboembolic complications in 832 patients with BCR-ABL-negative myeloproliferative neoplasms. Hamostaseologie. Published online October 9, 2023. doi:10.1055/a-2159-8767

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By Catlin Nalley

With ongoing advancements, the therapeutic landscape for myeloproliferative neoplasms continues to evolve. Naveen Pemmaraju, MD, Associate Professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, discussed where the field currently stands during his presentation, “Promising New Drugs for MPN Therapy,” at the International Congress on Myeloproliferative Neoplasms, held November 2-3, 2023, in New York.

When it comes to myeloproliferative neoplasms, “we have entered into a new golden era of research and potential that we have never seen before,” he noted. “Our field has been previously dominated by the first breakthrough—JAK inhibitor monotherapy—which was fantastic for our patients. However, as much of a revolution as this era was, by and large, it did not lead to cures of the disease. The only curative therapy as we close 2023 remains allogeneic stem cell transplant.”

In recent years, the field has seen breakthroughs with novel agents beyond the JAK/STAT pathway, according to Pemmaraju, who also highlighted the growing exploration of combination therapies in this patient population. “This is an important time in the MPN field,” he emphasized. “All of this is coming together, hopefully for the immediate good of our patients and then also establishing a new scientific era in myeloproliferative neoplasms,” he stated.

Main Takeaways

While discussing his presentation—and the MPN field as a whole—with Oncology Times, Pemmaraju highlighted a research study that explored life after ruxolitinib in myelofibrosis patients (Cancer 2020; doi: 10.1002/cncr.32664). Interestingly, he noted that the trial found that 40.8 percent of patients had stopped ruxolitinib at 3 years. Reasons for discontinuation included lack or loss of a spleen response, ruxolitinib-related adverse events, progression to blast phase, ruxolitinib-unrelated adverse events, and allogeneic transplantation during response.

The data also showed that the median survival after ruxolitinib was 13.2 months and the use of investigational agents was in fact associated with improved outcomes versus conventional agents, according to Pemmaraju, who noted this underscores the importance of ongoing investigation and advances.

In terms of combination treatments, Pemmaraju highlighted many different approaches, such as navitoclax, a BCL-XL/BCL-2 inhibitor. The potential of this agent has been explored in several studies, including the Phase II REFINE study (J Clin Oncol 2022; doi: 10.1200/JCO.21.02188). Data showed the addition of navitoclax to ruxolitinib among patients with persistent or progressive myelofibrosis led to durable spleen volume reduction, improved total symptom score, and hemoglobin response, reported Pemmaraju, an investigator on the trial.

Two phase III trials are currently underway to further explore the combination of navitoclax and ruxolitinib. The TRANSFORM-1 study is a frontline, upfront JAK inhibitor-naive study of ruxolitinib plus navitoclax versus ruxolitinib plus placebo. The other Phase III study, TRANSFORM-2, is looking at the efficacy and safety of this combination beyond the frontline setting.

Pemmaraju also highlighted several new novel agents that could have an impact on how we approach the treatment of MPNs. This includes but is not limited to agents that target the MDM2 pathway, telomerase inhibition, and cell cycle.

Additionally, he discussed another avenue targeting anemia in myelofibrosis. For instance, momelotinib was recently approved in September 2023 for intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post-polycythemia vera and post-essential thrombocythemia), in adults with anemia. Luspatercept is another example. This agent recently gained FDA approval for the treatment of anemia in myelodysplastic syndrome and is currently being studied in patients with myelofibrosis.

As the field evolves and advancements continue, Pemmaraju emphasized what is most important—the patient. “Everything we do is for our patients and every stakeholder has an important role to play,” he said. “Let’s continue to have awesome discoveries in the lab. Let’s pledge together to try to translate those quickly with all of our stakeholders who can help bring these findings to the clinic.

“And then, let’s make a pledge together to disseminate those findings accurately, faithfully, and rapidly through all platforms, not just academic literature, so that everyone can see these data in real time, debate, discuss, and have a say,” Pemmaraju concluded.

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Kristin Holl, Nicolas Chatain, Susanne Krapp, Anja Scheufen, Nathalie Brock, Steffen Koschmieder, Daniel Moreno-Andrés

Abstract
Myeloproliferative neoplasms (MPNs) encompass a diverse group of hematologic disorders driven by mutations in JAK2, CALR, or MPL. The prevailing working model explaining how these driver mutations induce different disease phenotypes is based on the decisive influence of the cellular microenvironment and the acquisition of additional mutations. Here, we report increased levels of chromatin segregation errors in hematopoietic cells stably expressing CALRdel52 or JAK2V617F mutations. Our investigations employing murine 32D MPL and human erythroleukemic TF-1MPL cells demonstrate a link between CALRdel52 or JAK2V617F expression and a compromised spindle assembly checkpoint (SAC), a phenomenon contributing to error-prone mitosis. This defective SAC is associated with imbalances in the recruitment of SAC factors to mitotic kinetochores upon CALRdel52 or JAK2V617F expression. We show that JAK2 mutant CD34 + MPN patient-derived cells exhibit reduced expression of the master mitotic regulators PLK1, aurora kinase B and PP2A catalytic subunit. Furthermore, the expression profile of mitotic regulators in CD34 + patient-derived cells allows to faithfully distinguish patients from healthy controls, as well as to differentiate primary and secondary myelofibrosis from essential thrombocythemia and polycythemia vera. Altogether, our data suggest alterations in mitotic regulation as a potential driver in the pathogenesis in MPN.

Introduction
Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg. MPNs) are a heterogeneous group of clonal hematopoietic disorders clinically subdivided into polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) [1]. The mutations in the genes of the Janus kinase 2 (JAK2), calreticulin (CALR), or the thrombopoietin receptor (TPOR/MPL) are driver mutations of these diseases [2, 3]. Their occurrence and variant allele frequency, together with specific bystander mutations, determine the clinical features, disease severity, and whether these disease evolve with dismal prognosis and decreased survival[3–6], towards secondary myelofibrosis (SMF), secondary acute myeloid leukemia and/or secondary solid tumors [7, 8]. The main pathogenic molecular signaling event of Ph-neg. MPNs is the constitutive activation of JAK2- STAT-dependent signaling pathways by mutations in CALR, JAK2 or the MPL receptor [2, 3]. Yet, noncanonical mechanisms of mutant JAK2[9], and CALR[10] have been recently linked to aspects of the disease pathology. However, the molecular mechanisms of the phase transition towards acute disease states are poorly defined [2, 5].

In contrast to other myeloid neoplasms such as primary acute myeloid leukemia (AML) [11, 12], myelodysplastic syndromes [13, 14] or chronic myeloid leukemia [15, 16], the cytology and molecular status of mitosis in Ph-neg. MPNs has not been studied in detail. However, karyotype abnormalities likely caused by chromatin segregation defects due to defective mitosis are present in up to 5% of ET, 20% of
PV, and 57% of PMF cases at the time of diagnosis [4, 17, 18] and accumulate over time, especially at blast-phase transformation[19–22] and frequently are associated with unfavorable prognosis and decreased survival[23–25]. Therefore, mitotic defects induced by driver Ph-neg. MPN mutations could play a role in the pathological mechanisms and contribute to the phase transition. Mitosis is tightly regulated by the crosstalk between the kinases Aurora B, CDK1 (cyclic dependent kinase 1)-Cyclin B1, and Polo-Like Kinase 1 (PLK1), and the protein phosphatase PP2A, as well as by the spindle assembly checkpoint (SAC) [26, 27]. The latter constitutes a protein network recruited to chromosome kinetochores to ensure proper chromosome-spindle attachments and accurate chromatin segregation. It includes several evolutionarily conserved proteins, like BubR1, Aurora B, MAD1, MAD2, MPS1, CDC20 and kinesin motor proteins, such as CENP-E, which are required for precise SAC function [26, 28]. Precise maintenance of the molecular equilibrium in gene expression and accurate subcellular positioning of these mitotic regulators play a critical role in preserving chromosome integrity and ensuring the stability of the karyotype [16, 28–30]. Consequently, defects in mitotic regulation promote chromosome instability (CIN), acquisition and evolution of heterogeneous karyotypes, inflammation, and epigenetic dysregulation. All these pathological mechanisms are linked to the malignant transformation in many solid cancers [31–33]. Similarly, hematological malignancies [16] such as AML [11, 12] and myelodysplastic syndromes [13, 14], show defects or dysregulation in crucial mitotic factors linked to CIN and heterogeneous karyotypes. Here, we have analyzed the mitotic cytology in murine and human cells stably expressing CALRdel52 or JAK2V617F and found error-prone mitosis. The examination of the molecular status of key mitotic regulators suggests defective SAC function. Also, CD34 + Ph-neg. MPN patient cells display differential expression profiles of a subset of important mitotic regulators, including the SAC components BUB1, MAD2L1, INCENP, CDC20, CDK1, PLK1 and Aurora A/B.

Results
CALRdel52 and JAK2V617F 32D MPL cells have a stresssensitive and error-prone mitosis To investigate chromatin segregation and the duration of mitosis, we performed long term live-cell imaging of murine 32D MPL cells (Fig. 1A) for a duration of 20 h followed by image analysis. In comparison with control 32D MPL (EV) cells, 32D MPL cells transduced with CALRdel52 or JAK2V617F showed a slight and non-significant increase in the numbers of chromatin bridges and lagging chromosomes (Fig. 1B). In contrast, the percentage of telophase micronuclei is significantly increased in the JAK2V617F mutant cell (p < 0.008, Fisher´s exact test). The occurrence of all three kinds of chromatin segregation errors further increases significantly in comparison to EV when DNA damage is induced with the chemotherapeutic agent doxorubicin [34] (p < 0.05, Fisher´s exact test), or SAC malfunction with the antimitotic drug NMS-P715 [35] (p < 0.02, Fisher´s exact test), which inhibits the checkpoint kinase MPS1 (Fig. 1B). The average mitotic timing in untreated cells or upon treatment with doxorubicin or MPS1 inhibitor is similar between mutants and control (EV) transfected cells (Supplementary Fig. S1). As expected, treatment the SAC inhibitor NMS-P715 reduced the mitotic timing with respect to untreated samples (Supplementary Fig. S1). These data suggest that mitosis in CALRdel52 and JAK2V617F mutant 32D MPL cells is stress sensitive. A weakened SAC contributes to error-prone mitosis in murine 32D
MPL CALRdel52 and JAK2V617F cells JAK2V617F [9, 36] and CALRdel52 [37] mutations have been linked to increased ROS production. In
addition, JAK2V617F is also linked to replication stress[38], and to lower p53 levels, a factor which is critical for the DNA damage response[39]. Replication stress and DNA damage signalling pathways, together with mitotic dysregulation, are well-known sources of karyotype aberrations such as aneuploidy, CIN, and genomic instability [40]. Therefore, we investigated whether the observed error-prone mitosis in CALRdel52 and JAK2V617F cells after doxorubicin treatment could be due to an altered response to DNA damage or replication stress.

First, we tested whether CALRdel52 or JAK2V617F transduced 32D MPL cells show increased levels of double-strand breaks during entry into mitosis as compared to control (EV) cells by immunofluorescence staining of γ-H2AX (H2AX S139ph) a well-described marker for DNA damage [41]. Visual inspection of γH2AX foci in untreated prometaphase EV and mutant cells revealed similar low levels of DNA damage. As
expected, the number of γ-H2AX foci increased to a similar extent in control (EV) and mutant cells after doxorubicin treatment (Supplementary Fig. S2A). In agreement with the literature [39], p53 basal levels in untreated JAK2V617F cells were much lower than in control EV cells or CALRdel52 (Supplementary Fig. S2B, Supplementary Figure S8). After doxorubicin treatment, p53 levels increased more than four-fold in all the cell lines. These results indicate that DNA damage is similarly induced by doxorubicin in control (EV) and mutant cells during mitotic entry and all cells showed a comparable functional stabilization of p53 after genotoxic stress. To test whether defects in SAC could contribute to the observed increase of chromatin segregation errors in CALRdel52 and JAK2V617F mutant cells, we challenged them with the spindle poison nocodazole. Cells with a weakened or defective SAC escape faster from the nocodazole induced mitotic arrest [29, 42]. Nocodazole treatment induced mitotic arrest in all three cell lines, but compared to control (EV) cells (257 ± 45 min), CALRdel52 (210 ± 36 min, p < 0.02 one-way ANOVA) or JAK2V617F (186 ± 35 min, p < 0.0001) transduced 32D MPL cells showed significantly shorter mitotic arrest and faster mitotic exit (Fig. 2A, B). The outcomes of mitotic arrest induced with microtubule inhibitors are diverse among cancer and normal cell lines due to the different pathways they induce [43, 44]. The current ‘competing networks-threshold’ model proposes that cell fate determination of – either cell death or extended survival – hinges on which of the two thresholds is reached first: either the activation of pro-apoptotic caspases or the degradation of cyclin B1 leading to mitotic slippage [43, 45]. To discriminate between these two options, we directly analyzed the fate of individual cells under mitotic arrest. The fraction of cells with mitotic death after mitotic arrest upon nocodazole treatment is very low (< 10%) and without significant differences between control (EV), CALRdel52, and JAK2V617F cells (two-way ANOVA with Dunnet post test) (Fig. 2C). In all conditions the arrested cells mostly escaped mitotic arrest by mitotic slippage without significant differences between the different cell types (two-way ANOVA with Dunnet post test) (Fig. 2C).

It has been proposed that murine cells are naturally more resistant than human cells to mitotic poisons due to the presence of clearance systems [46]. Therefore, we determined whether cyclin B1 accumulation was different between control (EV) and CALRdel52 or JAK2V617F cells after 3 hours of nocodazole treatment, which is the lower average time the cells (JAK2V617F cells, Fig. 2A) spend in mitotic arrest
before they undergo slippage. Cyclin B1 accumulated similarly in all three cell lines (Fig. 3A). Once accumulated, cyclin B1 was degraded faster in cells expressing CALRdel52 and JAK2V617F mutations (Fig. 3B; Supplementary Fig. S3; Supplementary Fig. S6) suggesting that a weakened SAC contributes to the error-prone mitosis in these cells.

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November 2, 2023

– Sixteen oral presentations, as well as a plenary session and poster presentations, highlight new advances across eight of the Company’s medicines

– Plenary Scientific Session will feature the full data from AGAVE-201 evaluating axatilimab, an anti-CSFR-1R monoclonal antibody, in patients with chronic graft-versus-host disease (GVHD)

– Incyte to host an in-person analyst and investor event on Monday, December 11, 2023 from 12:00-1:30 p.m. PT to discuss key data presentations at ASH

WILMINGTON, Del.–(BUSINESS WIRE)–Nov. 2, 2023– Incyte (Nasdaq:INCY) today announced that more than 40 abstracts highlighting data from eight of its hematology and oncology products will be presented at the upcoming 65^th American Society of Hematology Annual Meeting 2023 (ASH 2023), held December 9-12, 2023, in San Diego and virtually.

“We have continued to make significant progress in advancing our hematology and oncology pipeline with the goal to deliver better medicines for a range of diseases that have limited treatment options, including myeloproliferative neoplasms (MPNs) and chronic graft-versus-host disease (GVHD),” said Pablo J. Cagnoni, M.D., President and Head of Research and Development, Incyte. “We are excited to showcase the depth of our portfolio and clinical progress at this year’s ASH congress. In particular, we look forward to the presentation of the axatilimab AGAVE-201 trial results in patients with chronic GVHD at the Plenary Scientific Session, as well as the numerous oral and poster presentations including new data for our mutant CALR, BET, ALK2 and CK0804 programs in MPNs. Additionally, we are proud that the first presentation of data for INCB160058, our new potentially disease modifying JAK2V617F therapy for patients with MPNs, will be at this year’s meeting.”

Select key abstract presentations from Incyte-developed and partnered programs include:

Plenary Scientific Session

Axatilimab

Safety and Efficacy of Axatilimab at 3 Different Doses in Patients with Chronic Graft-Versus-Host Disease (AGAVE-201)¹ (Abstract #1. Plenary Scientific Session. Sunday, December 10, 5:00 p.m. – 7:00 p.m. ET)

Oral Presentations

Ruxolitinib (MPN)

A Real-World Evaluation of Risk Factors for Disease Progression in Patients with Polycythemia Vera (PV) Enrolled in REVEAL (Abstract #385. Session: 906. Outcomes Research – Myeloid Malignancies: Risk Factors and Health Disparities. Saturday, December 9, 7:00 p.m. ET)

Phase 1/2 Study of the Activin Receptor-Like Kinase-2 Inhibitor Zilurgisertib (INCB000928, LIMBER-104) as Monotherapy or with Ruxolitinib in Patients with Anemia Due to Myelofibrosis (Abstract #624. Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Charting The Future Of MPN Therapies. Sunday, December 10, 8:45 p.m. ET)

Bromodomain and Extra-Terminal (BET) Inhibitor INCB057643 (LIMBER-103) in Patients with Relapsed or Refractory Myelofibrosis (R/R MF) and Other Advanced Myeloid Neoplasms: A Phase 1 Study (Abstract #750. Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Treatment and Outcomes in MPNs. Monday, December 11, 2:45 p.m. ET)

Ruxolitinib (GVHD)

Ruxolitinib in Patients with Chronic Graft-Versus-Host Disease: Three-Year Final Analysis of Efficacy and Safety of the Phase 3 REACH3 Study² (Abstract #654. Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Innovative Approaches to GVHD Prevention and Treatment. Sunday, December 10, 8:45 p.m. ET)

Tafasitamab

Tafasitamab for the Treatment of Relapsed/Refractory (R/R) Diffuse Large B-cell Lymphoma (DLBCL) in the U.S. Real-World Setting (Abstract #265. Session: 905. Outcomes Research – Lymphoid Malignancies: Outcomes Research in Lymphoma/CLL: Biomarkers, Dosing Strategies, and Big-Data. Saturday, December 9, 5:00 p.m. ET)

Itacitinib

Itacitinib for the Prevention of Immune Effector Cell Therapy-Associated Cytokine Release Syndrome: Results from the Phase 2 INCB 39110-211 Placebo-Controlled, Randomized Cohort (Abstract #356. Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Prediction and Management of CAR-T Cell Related Toxicity. Saturday, December 9, 7:15 p.m. ET)

INCB160058

Preclinical Evaluation of INCB160058 – A Novel and Potentially Disease-Modifying Therapy for JAK2V617F Mutant Myeloproliferative Neoplasms (Abstract #860. Session: 631. Myeloproliferative Syndromes and Chronic Myeloid Leukemia: Basic and Translational: Lineage Tracing and Novel Target Discovery. Monday, December 11, 6:00 p.m. ET)

Poster Presentations

Ruxolitinib (MPN)

Effect of New or Worsening Anemia on Clinical Outcomes in 2,233 Patients with Myelofibrosis (MF) Treated with Ruxolitinib in the Expanded-Access JUMP Study (Abstract #5174. Session: 906. Outcomes Research—Myeloid Malignancies: Poster III. Monday, December 11, 9:00 p.m. – 11:00 p.m. ET)

Ruxolitinib Treatment in Polycythemia Vera Results in Reduction in JAK2 Allele Burden in Addition to Improvement in Hematocrit Control and Symptom Burden (Abstract #4553. Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster III. Monday, December 11, 9:00 p.m. – 11:00 p.m. ET)

High Rate of Disease Progression in Patients with Low-Risk Myelofibrosis (MF) Enrolled in the Prospective, Real-World, MOST Study Abstract #3803. Session: 906. Outcomes Research—Myeloid Malignancies: Poster II. Sunday, December 10, 9:00 p.m. – 11:00 p.m. ET)

Progression to Myelofibrosis in Patients with Essential Thrombocythemia: A Real-World Analysis from the Prospective MOST Study (Abstract #2433. Session: 906. Outcomes Research—Myeloid Malignancies: Poster I. Saturday, December 9, 8:30 p.m. – 10:30 p.m. ET)

Clinical and Disease Characteristics of Patients With Myelofibrosis and Essential Thrombocythemia that Harbor a Calreticulin (CALR) Gene Mutation: Subanalysis of the MOST Study (Abstract #3812. Session: 906. Outcomes Research—Myeloid Malignancies: Poster II. Sunday, December 10, 9:00 p.m. – 11:00 p.m. ET)

Comparison of the Enzymatic and Cellular Profiles of Clinical JAK2 Inhibitors for the Treatment of Myelofibrosis (Abstract #4532. Session: 631. Myeloproliferative Syndromes and Chronic Myeloid Leukemia: Basic and Translational: Poster III. Monday, December 11, 9:00 p.m. – 11:00 p.m. ET)

ALK2 and JAK2 Inhibition for Improved Treatment of Anemia in Myelofibrosis Patients: Preclinical Profile of an ALK2 Inhibitor Zilurgisertib in Combination with Ruxolitinib (Abstract #1789. Session: 631. Myeloproliferative Syndromes and Chronic Myeloid Leukemia: Basic and Translational: Poster I. Saturday, December 9, 8:30 p.m. – 10:30 p.m. ET)

The Association between Blood Cell Counts and Thrombotic Events in Japanese Patients with Polycythemia Vera: A Retrospective Database Study² (Abstract #3191. Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster II. Sunday, December 10, 9:00 p.m. – 11:00 p.m. ET)

Tafasitamab

Real-World Use of Tafasitamab (tafa) for Relapsed or Refractory (R/R) Diffuse Large B-cell Lymphoma (DLBCL) Among Racial and Ethnic Minorities in the United States (Abstract #2415. Session: 905. Outcomes Research – Lymphoid Malignancies: Poster I. Saturday, December 9, 8:30 – 10:30 p.m. ET)

Tafasitamab in Combination with a CD20xCD3 Bispecific T-cell Engager Significantly Prolongs Survival in Preclinical Lymphoma Models³ (Abstract #2813. Session: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II. Sunday, December 10, 9:00 – 11:00 p.m. ET)

Pemigatinib

Deep and Durable Cytogenetic and Molecular Responses with Pemigatinib in Myeloid/Lymphoid Neoplasms with Fibroblast Growth Factor Receptor 1 Rearrangement: The FIGHT-203 Study (Abstract #4551. Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster III. Monday, December 11, 9:00 p.m. – 11:00 p.m. ET)

Ponatinib

Long-term Results From the OPTIC Trial: A Dose-Optimization Study of 3 Starting Doses of Ponatinib⁴ (Abstract #3164. Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster II. Sunday, December 10, 9:00 – 11:00 p.m. ET)

Ponatinib Versus Imatinib in Patients with Newly Diagnosed Ph+ ALL: Subgroup Analysis of the Phase 3 PhALLCON Study⁴ (Abstract #2871. 614. Acute Lymphoblastic Leukemias: Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II. Sunday, December 10, 9:00 – 11:00 p.m. ET)

Itacitinib

Janus Kinase (JAK) 1 Inhibition Results in Significant Changes in Serum Proteins and Peripheral T-Cell Populations that Correlated with Clinical Scores in Chronic Graft-Versus-Host Disease (GVHD) Patients (an Analysis from GRAVITAS-309) (Abstract #2197. Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster I. Saturday, December 9, 8:30 – 10:30 p.m. ET)

Axatilimab

Axatilimab Ameliorates Inflammation and Fibrosis by Targeting the Macrophages in a Preclinical Model of Chronic GVHD (Abstract #2540. Session: 201. Granulocytes, Monocytes, and Macrophages: Poster II. Sunday, December 10, 9:00 – 11:00 p.m. ET)

CK0804

A Phase 1b, Open-Label Study of Add on Therapy with CK0804 in Participants with Myelofibrosis and Suboptimal Response to Ruxolitinib⁵ (Abstract #1813. Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I. Saturday, December 9, 8:30 – 10:30 p.m. ET)

More information regarding the congress is available on the ASH website: https://www.hematology.org/meetings/annual-meeting. This in-person event will be broadcast virtually and access to the meeting’s virtual platform is included with registration.

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