Study Supports Further Exploration of Tamoxifen in MPNs

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Sabrina Serani

Findings from a phase 2 study support the further investigation of tamoxifen (Soltamox), a selective estrogen receptor modulator (SERM), as a treatment option in patients with myeloproliferative neoplasms (MPNs), with extra consideration for thrombotic risk.1

A total of 38 patients with MPNs with mutated JAK2V617F, CALRins5, or CALRdel52 peripheral blood allele burden greater than 20% were recruited, and 32 patients completed 24 weeks of treatment. A greater than 50% reduction in mutant allele burden at 24 weeks was observed in 3 patients, and a 25% or greater reduction in mutant allele burden at 24 weeks was observed in 5 patients.

An exploratory analysis of hematopoietic stem/progenitor cell (HSPC) transcriptome identified a difference between responders and non-responders. Investigators observed that in responder HSPCs, there was a high baseline expression of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling and oxidative phosphorylation genes, which tamoxifen appeared to downregulate.

“The perfect segregation of the HSPC transcriptome from responders and non-responders at baseline could serve in the future as a platform for the stratification of patients based on their likelihood to respond to tamoxifen and for the identification of predictive biomarkers of response, if prospectively validated,” study authors wrote in findings published in Nature Communications.

“These results suggest that the metabolic effects of SERMs in cancer might be underappreciated and propose ways to modulate pathogenic JAK-STAT signaling through metabolic rewiring. These results warrant further investigation of tamoxifen as potential therapeutic for MPN in larger studies, after careful consideration of the risk of thrombosis,” study authors wrote.

Patients with essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (MF), post-PV MF, and post-ET MF were included in the study. The primary end point was a mutant allele burden reduction of greater than 50% at 24 weeks. The secondary end points included mutant allele burden reduction between 25% and 50% at 24 weeks, a greater than 50% reduction at 12 weeks, thrombotic events, toxicities, and hematological response.

Thrombotic adverse events (AEs) potentially related to tamoxifen were reported in 2 patients, and 1 patient discontinued treatment due to this AE. Investigators identified that the thrombotic events only occurred in non-responders, so identifying responders before initiating treatment should help reduce risks to patients.

Regarding safety, 11 additional patients discontinued study treatment due to toxicity. A grade 1 intracranial hemorrhage unrelated to tamoxifen was reported. No patient deaths were reported. Complete symptoms response was observed in 19% of patients, while 71.4% of patients had a partial symptom response, and 9.5% of patients had no response.

The results of this study warrant further exploration into tamoxifen as a treatment option for MPNs and further investigation of SERMs with lower thrombotic risks.

REFERENCES:
1. Fang Z, Corbizi Fattori G, McKerrell T, et al. Tamoxifen for the treatment of myeloproliferative neoplasms: A phase II clinical trial and exploratory analysis. Nat Commun. 2023;14(1):7725. Published 2023 Nov 25. doi:10.1038/s41467-023-43175-5

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Results from phase 1 of the MANIFEST clinical trial to evaluate the safety and tolerability of pelabresib in patients with myeloid malignancies

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Eytan M. Stein, Amir T. Fathi, Wael A. Harb, Gozde Colak, Andrea Fusco & James K. Mangan

 

ABSTRACT

Pelabresib (CPI-0610), a BET protein inhibitor, is in clinical development for hematologic malignancies, given its ability to target NF-κB gene expression. The MANIFEST phase 1 study assessed pelabresib in patients with acute leukemia, high-risk myelodysplastic (MDS) syndrome, or MDS/myeloproliferative neoplasms (MDS/MPNs) (NCT02158858). Forty-four patients received pelabresib orally once daily (QD) at various doses (24–400 mg capsule or 225–275 mg tablet) on cycles of 14 d on and 7 d off. The most frequent drug-related adverse events were nausea, decreased appetite, and fatigue. The maximum tolerated dose (MTD) was 225 mg tablet QD. One patient with chronic myelomonocytic leukemia (CMML) showed partial remission. In total, 25.8% of acute myeloid leukemia (AML) patients and 38.5% of high-risk MDS patients had stable disease. One AML patient and one CMML patient showed peripheral hematologic response. The favorable safety profile supports the ongoing pivotal study of pelabresib in patients with myelofibrosis using the recommended phase 2 dose of 125 mg tablet QD.

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Red Blood Cell Contribution to Thrombosis in Polycythemia Vera and Essential Thrombocythemia

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Julien Grenier, Wassim El Nemer, and Maria De Grandis

Abstract

Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms (MPN) characterized by clonal erythrocytosis and thrombocytosis, respectively. The main goal of therapy in PV and ET is to prevent thrombohemorrhagic complications. Despite a debated notion that red blood cells (RBCs) play a passive and minor role in thrombosis, there has been increasing evidence over the past decades that RBCs may play a biological and clinical role in PV and ET pathophysiology. This review summarizes the main mechanisms that suggest the involvement of PV and ET RBCs in thrombosis, including quantitative and qualitative RBC abnormalities reported in these pathologies. Among these abnormalities, we discuss increased RBC counts and hematocrit, that modulate blood rheology by increasing viscosity, as well as qualitative changes, such as deformability, aggregation, expression of adhesion proteins and phosphatidylserine and release of extracellular microvesicles. While the direct relationship between a high red cell count and thrombosis is well-known, the intrinsic defects of RBCs from PV and ET patients are new contributors that need to be investigated in depth in order to elucidate their role and pave the way for new therapeutical strategies.

SOHO State of the Art Updates and Next Questions | Diagnosis, Outcomes, and Management of Prefibrotic Myelofibrosis

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Pankit Vacchani, Sanam Lohgavi, Prithviraj Bose

Abstract

Prefibrotic primary myelofibrosis (prefibrotic PMF) is a myeloproliferative neoplasm with distinct characteristics comprising histopathological and clinico-biological parameters. It is classified as a subtype of primary myelofibrosis. In clinical practice, it is essential to correctly distinguish prefibrotic PMF from essential thrombocythemia especially but also overt PMF besides other myeloid neoplasms. Risk stratification and survival outcomes for prefibrotic PMF are worse than that of ET but better than that of overt PMF. Rates of progression to overt PMF and blast phase disease are also higher for prefibrotic PMF than ET. In this review we first discuss the historical context to the evolution of prefibrotic PMF as an entity, its presenting features and diagnostic criteria. We emphasize the differences between prefibrotic PMF, ET, and overt PMF with regards to presenting features and disease outcomes including thrombohemorrhagic events and progression to fibrotic and blast phase disease. Next, we discuss the risk stratification models and contextualize these in the setting of clinical management. We share our view of personalizing treatment to address unique patient needs in the context of currently available management options. Lastly, we discuss areas of critical need in clinical research and speculate on the possibility of future disease course modifying therapies in prefibrotic PMF.

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Prediction models for essential thrombocythemia from two longitudinal studies involving 2000 patients

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January 23, 2024

Tiziano Barbui and Alessandra Carobbio

Over the past two decades, significant progress has been made in several areas of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPNs), namely polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). The driver mutations in the JAK2-V617, MPL, calreticulin opened new diagnostic and prognostic possibilities and provided new targets for therapy [1].

ET is currently diagnosed according to the World Health Organization (WHO) [2] and International Consensus Criteria (ICC) [3] criteria, involving a comprehensive evaluation of clinical, laboratory and molecular features, and is defined by clonal thrombocytosis with characteristic bone marrow megakaryocyte morphology, which allows a differentiation from PV and prefibrotic myelofibrosis (pre-PMF); the latter is a distinct entity with a clinical picture often characterized by isolated thrombocytosis mimicking ET. In a multicenter series of 1104 patients previously classified as having ET, the diagnosis was re-evaluated following strict application of the 2008 WHO classification, which includes well-defined histopathological criteria. The diagnosis of ET was confirmed in 891 patients (81%) and revised to pre-PMF in 180 (16%) [4]. A subset of ET patients has a triple-negative (TN) genotype due to the absence of detectable mutations in driver genes and is observed in ~10% of ET cases [1].

Current information on risk factors of the major critical events (thrombosis, evolution to MF, blast phase (BP), and survival) derives from registry and multicenter observational studies while single-center reports conducted at tertiary referral institutions are very limited [5]. Each study design has its strengths and limitations. Observational multicenter studies and registries can capture a large number of cases but may face challenges related to data quality and consistency. Ensuring the accuracy and uniformity of data across multiple centers becomes a critical consideration.

Studies conducted in tertiary centers, exemplified by those presented in this Blood Cancer Journal issue from Florence [6] and Mayo Clinic [7] hospitals, are more robust in nature as they can provide a solid description of natural history of this myeloproliferative neoplasm. These are conducted by specialized teams comprising clinician hematologists, pathologists, geneticists, and other experts with proficiency in MPNs and are equipped with up-to-date technologies including molecular analyses, which are essential in the case of ET where genetic mutations play a significant role in diagnosis and prognosis. Nevertheless, despite providing comprehensive insights into a well-defined cohort of patients, these centers may have a patient referral bias and limited generalizability to the broader population. This may suggest that description of disease presentation and results on prognostic factors may not be universally reproducible, and caution should be exercised when extrapolating the results to consecutive patient groups.

The Mayo and Florence reports each included 1000 ET patients; all 2000 cases met ICC 2022 and WHO diagnostic criteria and were fully annotated for driver mutations; diagnosis required hematopathology review to minimize unintended inclusion of patients with masked PV or pre-PMF. This revision is critical for patients diagnosed with ET prior to the WHO recognition of masked PV and pre-PMF, as the incidence of complications such as thrombosis, myelofibrosis, blast phase, and overall survival differs between these entities compared to “true ET”. All patients in the two studies were annotated for driver mutations, which were found in approximately 90% of cases, with similar proportions in the two series for JAK2 V617F, CALR including CALR type 1/1-like and CALR type 2/2-like, MPL and TN. Interestingly, female sex clustered preferentially with TN and JAK2 vs. CALR/MPL mutations (p < 0.01), and extreme thrombocytosis clustered with CALR (type 2 more than type 1), TN, and MPL, whereas leukocytosis clustered with JAK2 mutation (p < 0.001). It is noteworthy that the two patients’ series from Mayo and Florence showed remarkably similar presentations over the extensive recruitment period of more than 40 years.

In these retrospective cohorts, 20% of patients had a history of vascular complications at diagnosis and a similar percentage of driver mutations clustered in a similar manner. Importantly, these findings are consistent with data observed in other real-world routine clinical practice of recent reviews on ET [8, 9]. This convergence of information on disease presentation between Mayo and Florence highlights that the characteristics of these two retrospective cohorts are unlikely to have been influenced by potential reference bias. Thus, the consistency of these patterns across different settings adds value to the findings of these two studies, reinforcing the reliability of the observed trends and minimizing the impact of referral bias.

Therefore, the Mayo and Florence longitudinal studies offer the unique advantage of capturing the dynamic evolution of ET disease in real-world clinical practice over an extended period of median 8.5 years (range, 0.01–52.7) and 8 years (range, 0.03–42.9), respectively, providing robust estimates of disease-specific outcomes, i.e., arterial and venous thrombosis, progression to overt MF, BP, and survival. This makes the results on risk factors for each of these critical events highly reliable and generalizable. In this context, the confirmation of the prognostic role of increased neutrophil granulocytes and decreased lymphocytes as independent risk factors for survival in 1164 ET patients should be highlighted. This new knowledge opens new avenues for future clinical trials on the role of inflammation in MPN and the associated new targets for therapy [10, 11]. In addition, the large number of cases annotated for driver mutations allowed the identification of risk scores for progression to myelofibrosis and blast phase and confirmed the predictive power of the International Prognostic Score of Thrombosis (IPSET-thrombosis) score. We agree with the authors that these results, obtained in a large series of patients with ET, mutually validated, can constitute a reference standard against which other series of cases fully annotated for driver mutations and followed up for a long time can be compared.

Inspired by the extensive ET series of these two Blood Cancer Journal papers, we reviewed our data on 891 WHO-diagnosed ET patients enrolled from multi-center institutions, in whom we investigated the effect of post-diagnosis intermediate events (thrombosis, MF, and BP) on mortality using multistate models [12]. Using these models, which increase the precision of estimation by correcting for competing risk factors, we found that patients with incident thrombosis had a progressively increased risk of death compared with patients without this event. As expected, the highest risk of death was associated with the occurrence of MF and BP (Fig. 1). Notably, in the time-dependent multivariate analysis, arterial but not venous thrombosis occurrence during follow-up was independently associated with death, together with evolution into MF and BP (Table 1). Therefore, in future analysis of longitudinal studies, we suggest that the conventional baseline prognostic evaluation in MPN should be revised by considering the intermediate events that might integrate the risk of the final outcome of interest in the single patient.

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A Rare Coexistence of Smoldering Multiple Myeloma and JAK2-Positive Myeloproliferative Neoplasm: A Case of Dual Synchronous Hematological Malignancy

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January 20, 2024

Abstract

This article explores the rare case of an 82-year-old man diagnosed concurrently with essential thrombocythemia and smoldering multiple myeloma (SMM). The limited existing literature on individuals harboring both myeloproliferative neoplasm (MPN) and monoclonal gammopathy (MG) is of significant interest due to the distinct origins of these malignancies. The etiology of MG in MPN patients remains elusive, leading to speculation about a potential relationship or interplay between the two conditions. This unique case prompts a deeper exploration of the mechanisms underlying the coexistence of JAK2-positive MPN and SMM. It underscores the importance of tailored therapeutic strategies that carefully consider the inherent risks and potential adverse outcomes associated with these specific malignancies, thereby warranting further clinical research.

Introduction

While existing literature acknowledges the coexistence of dual malignancies within the same patient [1], there is relatively limited documentation regarding the simultaneous occurrence of dual hematological malignancies (DHMs) [2,3], encompassing both myeloid and lymphoid hemopathies. A noteworthy aspect is the distinctive origin of these two malignancies from separate lineages within the hematopoietic ancestral tree [4]. DHMs can be classified as synchronous, manifesting within six months of the initial malignancy diagnosis, or asynchronous if they arise later [5].

Since its inclusion in the classification of monoclonal gammopathy (MG), smoldering multiple myeloma (SMM) has emerged as a significant aspect of MG [6], attracting attention in various clinical investigations.

Currently, no established strategies exist for treating or monitoring patients with myeloproliferative neoplasms (MPNs) and concurrent SMM. Additionally, the precise source of SMM in patients with MPN is not well understood, and there is uncertainty regarding whether an aberrant plasma cell condition arises from the identical hematopoietic clone as the MPN.

Numerous case reports have highlighted the occurrence of monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM) in patients with MPN, with details from only a limited number of patient cohorts published [7]. Remarkably, to date, there have been no reported instances of the concurrent diagnosis of essential thrombocythemia (ET) and SMM. In this report, we present a case of synchronous concurrent SMM and ET and provide a comprehensive review of the existing literature.

Case Presentation

An 82-year-old man with a history of hypertension and diabetes was referred to our department for the management of thrombocytosis. Physical examination revealed no remarkable findings, and there was no evidence of lymphadenopathy or hepatosplenomegaly. Laboratory results indicated a platelet count of 946 g/L, hemoglobin of 12.5 g/dL, and a white blood cell count of 6.4 g/L. The patient had no systemic symptoms.

Thrombocytosis workup was initiated, initially excluding infections and iron deficiency. The platelet count was notably elevated, suggesting uncommonly high levels for secondary causes of thrombocytosis.

The patient’s chemistry panel results are shown in Table 1. Monoclonal protein was measured at 36.6 g/L. Serum immunofixation electrophoresis revealed IgG lambda gammopathy. Free light chain lambda was elevated, and kappa was normal.

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Dr Vincelette on MYC Expression in Myelofibrosis

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Nicole D. Vincelette, PhD

Nicole D. Vincelette, PhD, postdoctoral fellow, Moffitt Cancer Center, discusses findings from a study investigating the role of MYC expression and S100A9-mediated inflammation in a subgroup of triple-negative myeloproliferative neoplasms (MPNs).

To determine how MYC expression drives MPNs, such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis, Vincelette and colleagues conducted a study in which they generated a mouse model that overexpresses MYC in the stem cell compartment. This analysis demonstrated that MYC overexpression was associated with the mice developing a myelofibrosis-like phenotype, which included anemia, atypical megakaryocytes, splenomegaly, bone marrow fibrosis, liver fibrosis, spleen fibrosis. The mice also experienced adverse clinical outcomes, such as reduced overall survival (OS), compared with wild-type mice, Vincelette says.

Since the MYC-overexpressed mice developed myelofibrosis, the next step of this research was to investigate how MYC drives myelofibrosis, Vincelette explains. Investigators performed single-cell RNA sequencing to compare the bone marrow cells from MYC-overexpressed and wild-type mice. MYC overexpression correlated with upregulation of the S100A9 protein, which contributes to inflammation and innate immunity, according to Vincelette. Therefore, MYC drives the development of myelofibrosis through S100A9-mediated chronic inflammation. To validate the role of S100A9 downstream of MYC in myelofibrosis, investigators created a mouse model with S100A9 knockout in the presence of MYC overexpression, Vincelette notes. The S100A9 knockout protected against the development of myelofibrosis phenotype in that mouse model, Vincelette emphasizes.

By generating a mouse model that overexpresses S100A9, investigators also determined that S100A9 overexpression alone contributes to the development of myelofibrosis phenotypes, Vincelette says. When investigators treated the MYC-overexpressing mice with the S100A9 inhibitor tasquinimod (ABR-215050), the agent only partially abrogated the myelofibrosis phenotype, meaning the mice had reduced atypical megakaryocytes and splenomegaly. Additionally, the mice developed anemia and no OS difference occurred between tasquinimod and vehicle treatment, potentially because of off-target drug effects, Vincelette concludes.

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The role of inherited genetic variants in rare blood cancer

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January 17, 2024

Researchers from the University of Cambridge, Wellcome Sanger Institute, and collaborators have shown how inherited genetic variants can influence the risk of developing a rare blood cancer.

Large-scale genetic analysis has helped researchers uncover the relationship between cancer-driving genetic mutations and inherited genetic variants in a rare type of blood cancer.

The team combined datasets to understand the impact of cancer-driving spontaneous mutations and inherited genetic variation on the risk of developing myeloproliferative neoplasms (MPN).

Published in Nature Genetics, the study describes how inherited genetic variants can influence whether a spontaneous mutation in a particular gene increases the risk of developing this rare blood cancer.

The analysis will have an impact on current clinical predictions of disease development in individuals.

More research is needed to understand the mechanisms behind how the inherited genetic variants influence the probability of developing rare blood cancer.

In the future, the work could aid drug development interventions that reduce the risk of disease.

Myeloproliferative neoplasms

MPNs are a group of rare and chronic blood cancers, with around 4,000 cases in the UK each year. These occur when the bone marrow overproduces blood cells, resulting in blood clots and bleeding.

MPNs can also progress into other forms of blood cancer.

Genetic risk score

There is a large amount of natural variation between individuals’ blood cells which can affect the amount of blood cells a person has and their traits. This is because different genes can influence blood cell features in an individual.

Researchers take known information about these genes during routine blood tests and analyse the variation to give a genetic risk score. This is how likely that individual is to develop a disease over their lifetime.

MPNs have been linked to random somatic mutations in a gene called JAK2; however, mutated JAK2 is commonly found in the global population. The vast majority of these individuals do not have or go on to develop MPN.

Previous studies identified over a dozen associated inherited genetic variants that increase the risk of MPN. However, these studies do not explain why most individuals do not go on to develop MPN.

Inherited genetic variants can influence risk

The new study combined information on the known somatic driver mutations in MPN inherited genetic variants, and genetic risk scores from individuals with MPN.

They found that the inherited genetic variants that cause natural blood cell variation in the population also impact whether a JAK2 somatic mutation will cause MPN. The team also discovered that individuals with an inherited risk of having a higher blood cell count could display MPN features in the absence of cancer-driving mutations, mimicking disease.

Dr Jing Guo, from the University of Cambridge and the Wellcome Sanger Institute and first author of the study, said: “Our large-scale statistical study has helped fill the knowledge gaps in how variants in DNA, both inherited and somatic, interact to influence complex disease risk.

“By combining these three different types of datasets we were able to get a more complete picture of how these variants combine to cause blood disorders.”

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Fedratinib Improves Myelofibrosis Management Compared With Ruxolitinib

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By Patrick Daly – Last Updated: January 17, 2024

Treatment with fedratinib, a Janus kinase inhibitor (JAKi), induced superior spleen volume reduction (SVR) and symptom response rates compared with best available therapy in patients with myelofibrosis (MF) who previously received ruxolitinib, according to data from the open-label phase III FREEDOM2 study, presented at the 65th American Society of Hematology Annual Meeting & Exposition.

“Most patients on best available therapy received ruxolitinib, highlighting a need for an alternative JAKi,” stated lead author of the study, Claire Harrison, MD, FRCP, from Guy’s and St. Thomas’ NHS Foundation Trust in London, England.

The FREEDOM2 trial enrolled patients aged 18 years or older with primary, post-polycythemia vera, or post-essential thrombocythemia MF with splenomegaly who were intolerant or refractory to, or relapsed after ruxolitinib. The primary endpoint was SVR ≥35% (SVR35) at the end of the sixth 28-day cycle.

Fedratinib for Myelofibrosis Treatment Superior to Ruxolitinib

In total, 201 patients were randomized to fedratinib (n=134) or best available therapy (n=67). The cohort had a median age of 70 (interquartile range, 64-74), 52.2% were male, 54.7% had primary MF, and 76.1% had a Dynamic International Prognostic Scoring System risk score of intermediate-2.

Overall, 70.1% of patients in the best available therapy arm received ruxolitinib, 10.4% received hydroxyurea, and 7.5% received ruxolitinib plus hydroxyurea. Additionally, 46 (68.7%) patients in the best available therapy arm crossed over to fedratinib after either disease progression or the sixth cycle response assessment.

With a median follow-up of 15 months at the data cutoff, researchers reported the fedratinib group had a significantly higher SVR35 rate of 35.8% at the end of cycle six compared with best available therapy at 6.0% (P<.0001). Fedratinib also yielded superior SVR ≥25% at the cycle six assessment and superior SVR35 at any point during treatment. The rate of symptom response at the end of cycle six was 34.1% with fedratinib versus 16.9% with best available therapy (P=.0033).

In short, “fedratinib demonstrated superior SVR and symptom response rates compared with [best available therapy]” in patients with MF and prior ruxolitinib treatment, concluded Dr. Harrison and colleagues.

Reference

Harrison CN, Mesa RA, Talpaz M, et al. Efficacy and safety of fedratinib in patients with myelofibrosis previously treated with ruxolitinib: results from the phase 3 randomized FREEDOM2 study. Abstract #3204. Presented at the 65th ASH Annual Meeting & Exposition; December 9-12, 2023; San Diego, California.

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CALR-Mutated Essential Thrombocythemia Associated With Higher Progression to Myelofibrosis Risk

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CALR mutations in essential thrombocythemia are associated with lower thrombosis risk and higher risk of progression to myelofibrosis (MF) compared with other driver mutations, according to a recent study.

The study was led by Katie Erdos, a Research Program Assistant at Weill Cornell Medicine’s Richard T. Silver, MD Myeloproliferative Neoplasms Center, and presented at the 65th American Society of Hematology Annual Meeting & Exposition.

Erdos and colleagues conducted the study to evaluate the impact of driver mutations on the risks of thromboembolic events, disease progression, and patient mortality.

Of 338 total patients, 216 (64%) were positive for JAK2V617F, 85 (25%) were positive for CALR, 19 (6%) were positive for MPL, and 18 were (5%) triple-negative (TN). Red cell parameters were slightly higher in patients with JAK2V617F mutations (P<0.001), white blood cell count was highest in TN patients (P=0.012), and platelet count did not significantly vary across mutation groups (P=0.064).

The 20-year thrombosis-free survival was 71% for JAK2V617F, 100% for CALR, 90% for MPL, and 83% for TN (P=0.0027). The 20-year MF-free survival was 87% for JAK2V617F, 48% for CALR, 65% for MPL, and 94% for TN (P=0.00053). Meanwhile, the 20-year overall survival was 76% for JAK2V617F, 86% for CALR, 89% for MPL, and 90% for TN (P=0.66).

“Our findings reinforce the need for long-term data to guide therapy for ET based not only on the near-term thrombotic risk, but also on the long-term risk of progression,” wrote Erdos and colleagues.

Reference

Erdos K, Lee N, Lebbe A, et al. Low thrombosis risk CALR mutations confer higher risk of essential thrombocythemia progression. Abstract #1819. Presented at the 65th ASH Annual Meeting & Exposition; December 9-12, 2023; San Diego, California.

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