JAB-8263 Monotherapy Demonstrates Early Promise in Myelofibrosis

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December 13, 2024

Author(s): Kristi Rosa

The investigative BET inhibitor JAB-8263 was found to be well tolerated and to demonstrate preliminary efficacy in patients with myelofibrosis, according to data from a phase 1/2 study (NCT04686682) presented during the 2024 ASH Annual Meeting.1

Any treatment-emergent adverse effects (TEAEs) occurred in 93.8% of those who received the agent at any dose level (n = 16), with 37.5% experiencing grade 3 or higher TEAEs and 25.0% experiencing a serious TEAEs. Treatment-related AEs (TRAEs) occurred in 87.5% of patients, with 31.3% experiencing grade 3 or higher TRAEs, and 18.8% experiencing serious TRAEs. TRAEs led to dose interruption and reduction for 43.8% and 25.0% of patients, respectively. One patient experienced a TRAE that led to discontinuation of JAB-8263. No treatment-related events proved to be fatal.

Notably, 1 dose-limiting toxicity occurred in a patient who received the agent at a dose of 0.4 mg; this patient experienced grade 3 increases in alanine and aspartate aminotransferase levels.

In all evaluable patients (n = 13), the mean spleen volume reduction (SVR) was –19.95% (range, –39.4% to 3.6%) at week 24 and –26.16% (range, 56.6% to –11.0%) at best response. Notably, 2 patients achieved an SVR of 35% or higher, and 1 patient experienced an SVR of –34.9%. Moreover, at week 24, 60% of 10 patients had a tumor symptom score reduction of at least 50% (TSS50). Two of 8 patients who had received JAK inhibitors experienced a best response of SVR of –41.2% and 34.9%, respectively. Moreover, 50% of 6 evaluable patients who had received JAK inhibitors achieved TSS50 at week 24.

“JAB-8263 at 0.125 mg [once daily to] 0.3 mg [once daily] was well tolerated…Hematological and gastrointestinal AEs are mild with JAB-8263 continuous dosing [compared with] other BET inhibitors,” Junyuan Qi, MD, of the Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences, in Tianjin, China, and coauthors, wrote in the poster of the data. “The preliminary efficacy data in myelofibrosis for JAB-8263 monotherapy is promising. Most patients showed spleen reduction and TSS reduction.”

The early-phase study enrolled patients with confirmed primary myelofibrosis (PMF), post–polycythemia vera myelofibrosis (PV-MF), or post–essential thrombocytopenia myelofibrosis (ET-MF). Patients were at least 18 years of age, had spleen volume of at least 450 cm3, a Dynamic International Prognostic Score (DIPSS) of at least intermediate-1, and an ECOG performance status up to 2.

The median age in the 16 total patients was 62 years (range, 36-69) and 56.3% were female. All patients were Asian. Regarding ECOG performance status, 31.3% had a status of 0, 62.5% had a status of 1, and 6.3% had a status of 2. Regarding disease subtype, 68.8% of patients had PMF, 18.8% had PV-MF, and 12.5% had ET-MF. Half of patients had prior exposure to a JAK inhibitor. Most patients had a JAK2 mutation (93.8%). Regarding DIPSS, 68.8% had intermediate-1 disease and 25.0% had intermediate-2 disease. The median time since initial diagnosis was 13.5 months (range, 0.9-76.6).

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MAIC Points to Improved OS With Momelotinib in Ruxolitinib-Pretreated Myelofibrosis

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December 13, 2024

Author(s): Caroline Seymour, Kyle Doherty

Fact checked by: Courtney Flaherty

Momelotinib (Ojjaara) demonstrated improved overall survival (OS) vs best available therapy (BAT) in patients with ruxolitinib (Jakafi)–pretreated myelofibrosis, according to data from a matching-adjusted indirect comparison (MAIC) analysis that were presented at the 2024 ASH Annual Meeting & Exposition.1

Data from an unmatched analysis demonstrated that the median OS favored patients who received momelotinib (n = 383) compared with those who received BAT (n = 267; HR, 0.373; 95% CI, 0.297-0.469; P < .001). In the base case model (model 1), the median OS also favored momelotinib (n = 89) vs BAT (HR, 0.512; HR, 0.358-0.732; P < .001). In the alternative adjustment model (model 2), the median OS again favored momelotinib (n = 117) vs BAT (HR, 0.484; 95% CI, 0.347-0.675; P < .001).

Additionally, patients in the anemia subgroup who received momelotinib (n = 255) experienced a median OS benefit compared with those treated with BAT (n = 174; HR, 0.384; 95% CI, 0.293-0.504; P < .001). Data from model 1 also showed that patients treated with momelotinib in this subgroup (n = 98) achieved a median OS benefit vs those in the BAT arm (HR, 0.542; 95% CI, 0.387-0.759; P < .001). Findings from model 2 demonstrated a median OS benefit with momelotinib (n = 146) vs BAT (HR, 0.487; 95% CI, 0.360-0.660; P < .001).

“[Although] the trials used in this analysis do no provide long-term outcomes, this MAIC suggests that momelotinib may offer a greater OS benefit than BAT in patients with myelofibrosis previously treated with ruxolitinib, both in the overall cohort and the anemic population,” Francesca Palandri, MD, PhD, lead study author and an adjunct professor in the Department of Medical and Surgical Sciences at the University of Bologna in Italy, said in a poster presentation of the data.

In September 2023, the FDA approved momelotinib for the treatment of adult patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis, and anemia.2 The regulatory decision was supported by findings from the phase 3 MOMENTUM (NCT04173494) and SIMPLIFY-1 trials (NCT01969838).

To conduct their analysis, Palandri and colleagues performed a MAIC analysis comparing patients who received momelotinib during MOMENTUM, SIMPLIFY-1, or the phase 3 SIMPLIFY-2 trial (NCT02101268) with 267 patients who received BAT across 26 European hematology centers in the real-world, retrospective RUX-MF study.1 Notably, the overall study included 1055 patients treated with ruxolitinib across 26 European hematology centers from 2013 until death or the data cutoff of February 2, 2024.

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Pacritinib and Momelotinib Display Positive Real-World Impact on Anemia and Transfusion Needs in Myelofibrosis

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December 12, 2024

Author(s): Kyle Doherty

Fact checked by: Caroline Seymour

Although long-term follow-up was limited, treatment with the JAK2 inhibitors pacritinib (Vonjo) and/or momelotinib (Ojjaara) led to favorable effects on anemia and transfusion requirements among patients with myelofibrosis, according to findings from a real-world study presented in a poster during the 2024 ASH Annual Meeting.1

Patients who received momelotinib (n = 32) had a median hemoglobin count of 8.7 g/dL (range, 6.5-1.2) at the start of therapy which increased to 9.0 g/dL after 3 months of treatment (P = .021). The median platelet count at the start of therapy was 141 x 109/L (range 15 x 109-504 x 109) and increased to 116 x 109/L after 3 months (P = .317). Patients required a mean of 1.9 red blood cell (RBC) units/month at the start of therapy and 0.47 units/month after 3 months of treatment (P = .015).

Patients treated with pacritinib (n = 27) had a median hemoglobin count of 8.5 g/dL (range, 6.9-12.9) at the start of treatment and a median count of 9.1 g/dL following 3 months of therapy (P = .402). The median platelet count at the start of therapy was 65 x 109/L(range, 18 x 109-441 x 109) compared with 31 x 109/L after 3 months of treatment (P = .303). Patients required a mean of 2.4 RBC units/month at the start of therapy vs 0.75 RBC units/month after 3 months of therapy (P = .099).

“The goal of this project was to [examine] the patients who have been treated so far at Moffitt Cancer Center with either pacritinib and/or momelotinib to gain a better understanding of the hematologic responses of these therapies, the duration of treatment, and other real-world data regarding these agents after they got their approvals,” Jeremy DiGennaro, MD, said during the presentation. “Patients receiving momelotinib and pacritinib are typically older with extended disease duration, multiple prior lines of therapy, high-risk mutations, and cytopenia. Pacritinib-treated patients have more prominent baseline thrombocytopenia. [However], there were favorable impacts on anemia and transfusion requirements [with both agents], although we still do need more long-term follow-up.”

DiGennaro is an internal medicine resident physician at the University of South Florida Morsani College of Medicine in Tampa.

In February 2022, the FDA granted accelerated approval to pacritinib for the treatment of adult patients with intermediate or high-risk primary or secondary myelofibrosis with a platelet count below 50,000/µL.2 Momelotinib was approved by the FDA in September 2023 for the treatment of adult patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis, and anemia.3

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Optimizing Myelofibrosis Care in the Age of JAK Inhibitors

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December 12, 2024|Hematology and Oncology
Douglas Tremblay, MD

Myelofibrosis is a rare but serious bone marrow disorder that disrupts blood cell production and often leads to debilitating symptoms. In this interview, Douglas Tremblay, MD, Assistant Professor at the Tisch Cancer Institute, discusses the process for selecting the best treatment pathway for patients – from evaluating disease prognosis to navigating treatment resistance and intolerance.

Dr. Douglas Tremblay

How do you assess a patient’s prognosis at the time that they are diagnosed with myelofibrosis?
In the clinic, we use several scoring systems that have been developed based on the outcomes of hundreds of patients with myeloproliferative neoplasms (MPNs) to try to predict survival from time of diagnosis. Disease features associated with a poor prognosis include anemia, elevated white blood cell count, advanced age, constitutional symptoms, and increased peripheral blasts. Some of these scoring systems also incorporate chromosomal abnormalities as well as gene mutations to further refine prognostication.1

Determining prognosis can be important to creating a treatment plan, particularly to decide if curative allogeneic stem cell transplantation is necessary. However, I always caution patients that these prognostic scoring systems cannot tell the future and that each patient may respond differently to treatment.

How do you monitor for disease progression?
I will discuss with patients how they are feeling in order to determine if there are any new or developing symptoms that could be a sign that their disease is progressing. I will also review their laboratory work looking for changes in blood counts that could be a signal of disease evolution.

For instance, development of anemia or thrombocytopenia may signal worsening bone marrow function or progression to secondary acute leukemia. If there are concerning signs or symptoms, I will then perform a bone marrow biopsy with aspirate that will include assessment of mutations and chromosomal abnormalities to determine if their disease is progressing.

What are the first-line treatment options for a patient newly diagnosed with myelofibrosis, and how do you determine the best course of action?
For patients with myelofibrosis, the first-line treatment options include Janus kinase (JAK) inhibitors, which are effective at improving spleen size and reducing symptom burden. The US Food and Drug Administration (FDA) has approved 4 JAK inhibitors for the treatment of myelofibrosis: ruxolitinib, fedratinib, pacritinib, and momelotinib (Table).2-13 In general, ruxolitinib is the first-line treatment option unless there is thrombocytopenia, in which case pacritinib is more appropriate. In patients with baseline anemia, momelotinib may be the best choice.

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In Myeloid Neoplasms, Next-Generation Sequencing Can Be Inappropriate—and Money-Wasting

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December 12, 2024

Author(s): Gayle Turim Dickstein

Using more careful consideration when deciding whether or not to order next-generation sequencing (NGS) for a patient with an actual or suspected myeloid neoplasm (MN) could save institutions thousands of dollars annually without compromising care, according to a Yale School of Medicine team. They have created a set of criteria to determine the appropriateness of NGS testing for MN (MN-NGS), with the goal of maximizing actionable results. Writing in eJHaem, the team also noted that the results of NGS, when not clinically indicated but performed anyway, can foster fruitless investigative paths and amplify patient anxiety.1

Close-up illustration of a MN | image credit: sawaratch – stock.adobe.com

They noted that, indeed, MNs often harbor pathogenic mutations that go undetected by karyotyping and fluorescence in situ hybridization, and NGS is truly necessary for diagnosis, risk stratification, and therapy.2 Among the 6 situations that would, if present, warrant NGS (ie, approval criteria) would be clinical suspicion of new, relapsed, or worsening disease, and end-of-induction chemotherapy.

The 6 “cancellation criteria”—situations in which these investigators say NGS clearly should not be performed—include, first, having a suspicion of only nonmyeloid disease (ie, the diagnosis is a nonmyeloid disease, or there is no suspicion for acute myeloid leukemia [AML], myelodysplasia, myeloproliferative neoplasm [MPN], or another MN). Other situations are having no suspicion of progression of a known MN; no evidence for recurrence post-transplant; a diagnosis of chronic myeloid leukemia (CML) with no concern for AML; and cases using blood when a concurrent bone marrow NGS is being performed. The 6th and final criterion is that none of the above cancellation criteria have been met, but no approval criteria have been met either.

The actionable results that should emerge from NGS done for the proper reason include making a new MN diagnosis, characterizing a MN with baseline mutational status for follow-up purposes, and altering a patient’s treatment plan, noted the investigators.

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Fedratinib Alleviates Symptoms, Reduces Spleen Volume in MDS, MPNs

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Megan Garlapow, PhD

Fedratinib can reduce symptoms and spleen volume in patients with myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPNs), according to research presented at the ASH Annual Meeting 2024.

Researchers are evaluating fedratinib, a JAK2 inhibitor, in a phase 2 trial. The trial (NCT05177211) enrolled 25 patients with atypical chronic myeloid leukemia (n=6), chronic neutrophilic leukemia (n=5), MDS/MPN-unclassifiable (n=8), and MDS/MPN with ring sideroblasts and thrombocytosis (n=6).

At baseline, the median patient age was 68.8 (range, 39.9-84.7) years, and the median time from diagnosis to treatment was 7.1 months. Most patients had splenomegaly (83%), and the median MPN-Symptom Assessment Form Total Symptom Score was 21 (range, 1-73). Prior treatments included hydroxyurea (36%), ruxolitinib (20%), luspatercept (8%), and hypomethylating agents (12%). Patients had a median of 3 pathogenic mutations.

“Most of these patients had multiple mutations, and most had a signaling mutation, an epigenetic mutation, and a splicing mutation,” said study presenter Andrew Kuykendall, MD, of the Moffitt Cancer Center in Tampa, Florida.

The patients received fedratinib at a dose of 400 mg daily in 28-day cycles. They could continue on treatment as long as they had a clinical benefit. At last follow-up, 11 patients were still on study treatment.

The median duration of fedratinib treatment was 10.8 months, and 21 patients were evaluable for efficacy at 24 weeks. Three patients discontinued fedratinib prior to 24 weeks for reasons unrelated to toxicity or lack of efficacy (eg, cost) and were considered non-responders.

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Genetic Links to High Altitude Found to Reduce Inflammation, Speed Response to PV Therapy

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December 10, 2024

Author(s): Mary Caffrey

Questions about why an indigenous population living the Andes Mountains of South American had elevated hemoglobin led to the discovery that a variant linked to living at high altitude is also tied to reduced inflammation, as well as improved response to a therapy used to treat myeloproliferative neoplasms (MPNs).1

Jihyun Song, PhD | Image credit: University of Utah

The research to be presented today at the 66th American Society of Hematology Annual Meeting & Exposition in San Diego, California, could lead to more precise treatments for polycythemia Vera (PV) and essential thrombocythemia (ET). Today, these 2 are treated with ropeginterferon-α (Besremi), and the work led by Jihyun Song, PhD, of Huntsman Cancer Institute at the University of Utah, now shows that populations with Andean enriched NFKB1 haplotype respond better to ropeginterferon-α.

The study has been accepted for publication in Nature Communications.

PV and ET are both associated with overproduction of blood cells; PV causes the bone marrow to produce too many red blood cells, while ET produces too many platelets. Both PV and ET can lead to chronic inflammation, increase the risk of blood clots, and progress to leukemia. These conditions also increase hypoxia-inducible factors (HIFs), which can impact the survival of cancer cells in low-oxygen environments.

At a press briefing prior to Song’s presentation today, senior author Josef T. Prchal, MD, a physician scientist who holds the Charles A. Nugent, MD, and Margaret Nugent Endowed Professorship in Medicine/Hematology at the University of Utah, explained that the genetic variants that developed over time to allow the Aymara people survive in the Andes can be seen in some other populations—and they correlate with some differences in MPN phenotypes.

Josef Prchal, MD | Image credit: Photo supplied by ASH

“Our study suggests that with genotyping, the NFKB1 variant can be used as a biomarker for determining which patients may be more or less responsive to ropeginterferon-α treatment,” Prchal said.

He opened his remarks with an overview of how populations evolve with their environments; not only the Aymara but also Tibetans and Ethiopians have adapted to altitude in different ways, which he explored in earlier papers in Science2 and Nature Genetics,3 among others.

It is known that when humans spend time high altitude, their bodies adapt to reduced oxygen levels by increasing hemoglobin concentrations in the blood. This allows the body to carry more oxygen. Prchal explained how Song took this knowledge further. “We set up to try to find the gene which explains the hemoglobin,” he said.

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Navtemadlin Reduces Markers of Disease Burden in Relapsed/Refractory Myelofibrosis

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December 9, 2024

Author(s): Morgan Bayer

Treatment with navtemadlin (KRT-232) lowered the levels of biomarkers of disease burden in patients with relapsed/refractory myelofibrosis, according to findings from the phase 3 BOREAS trial (NCT03930732) that were presented at the 2024 ASH Annual Meeting.1

“I want to emphasize the biology that drives this approach. MDM2 is a negative regulator of wild-type p53, which is a master determinant of cell fate, and this becomes very critical when you consider its influence over the 4 hallmarks of myelofibrosis: CD34-positive myelofibrosis cell proliferation, myelofibrosis driver gene variant allele frequency (VAF), bone marrow fibrosis, and pro-inflammatory cytokines,” said John O. Mascarenhas, MD, during a presentation of the data.

Mascarenhas is professor of medicine, hematology and medical oncology, director of the Center of Excellence for Blood Cancers and Myeloid Disorders, and director of the Adult Leukemia Program at the Mount Sinai Tisch Cancer Center in New York, New York.

In the randomized, multicenter, global phase 3 BOREAS trial, navtemadlin monotherapy was compared with best available therapy (BAT) that included hydroxyurea, peginterferon, immunomodulatory drugs, or supportive care. Patients included in the trial had TP53 wild-type myelofibrosis and were refractory or had relapsed on prior therapy with a JAK inhibitor. The data cutoff date was September 30, 2024.

In the study, 183 patients were randomly assigned 2:1 to receive navtemadlin (n =1 23) at 240 mg 7 days in a row for a 28-day cycle (with 21 days of drug holiday) or 1 cycle of BAT (n = 60) for 28 days. “The patients who were on a JAK inhibitor at the time had a 28-day washout period so that from a spleen and symptom perspective they were clear on day 1 of navtemadlin dosing,” Mascarenhas explained.

“What we saw in terms of biomarkers was a very significant potent, rapid reduction in circulating CD34 cells as a hallmark of myelofibrosis even within 12 weeks and sustained over 24 and 36 weeks,” Mascarenhas stated. At 12 weeks, CD34-positive cells showed a median reduction of 68% from baseline in 50 patients in the navtemadlin arm and 52% in 25 patients in the BAT arm. This trend continued at 24 weeks (n = 48, 70% reduction vs n = 19, 38% reduction) and at 36 weeks (n = 21, 76% reduction vs n = 9, 33% reduction).

The reduction in driver gene VAF by 50% or greater was observed in 21% (n = 17/82) of patients in the navtemadlin arm and 12% (n = 4/33) of patients in the BAT arm at 24 weeks, “nearly doubling the molecular response at 24 weeks,” Mascarenhas noted.

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Prognostic Implications of Pulmonary Hypertension in Myeloproliferative Neoplasms and Predictors of Hematologic Progression

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Orly Leiva, MD, Steve Soo, MD, Nathanial Smilowitz, Harmony Reynolds, Binita Shah, Samuel Bernard, Michelle Hyunju Lee, MD, Chi-Joan How, MD, and Gabriela S. Hobbs, MD

Introduction:
Myeloproliferative neoplasms (MPNs), which include essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are a group of disorders of clonal hematopoiesis associated with increased risk of cardiovascular disease (CVD), including pulmonary hypertension (PH). In a prior study of patients with MPN and established CVD, PH was associated with increased risk of hematologic progression to secondary MF or acute leukemia and major adverse cardiovascular events (MACE). However, the prognostic implication of PH among patients with MPN regardless of prior CVD status is unclear. Furthermore, transthoracic echocardiographic (TTE) characterization of risk of hematologic progression among those with PH has not been well studied.
Methods:
This was a multicenter retrospective cohort study of MPN patients with ≥ 1 TTE after diagnosis of MPN at New York University Langone Health and Massachusetts General Hospital from 2010 to 2023. PH was defined as estimated pulmonary artery systolic pressure (PASP) ≥ 40 mmHg on first TTE after MPN diagnosis. The primary outcome was a composite hematologic outcome of progression to secondary MF, acute leukemia, or death from MPN. Secondary outcome was MACE, a composite of arterial or venous thrombosis, heart failure (HF) hospitalization, or CV death. Given the competing risk of death, multivariable Fine-Gray competing-risk regression was used to estimate subhazard ratio (SHR) of the primary and secondary outcomes, and were adjusted for age at first TTE, MPN type, driver mutation, any non-driver mutation status, time from MPN to TTE, hemoglobin and WBC concentration, and spleen size. The association between PH and MACE was further adjusted for treatment for the MPN, left ventricular ejection fraction (LVEF), prior CVD, indication/setting of TTE, diastolic dysfunction, anti-thrombotic use, statin use, and creatinine. Hemodynamic predictors of the composite hematologic outcome among patients with PH was assessed using univariate competing-risk regression. Variables that were significantly different between groups (p < 0.05) were adjusted for age, time from MPN to TTE, driver and non-driver mutations, and spleen size.
Results:
Of the 555 patients included, 42.7% had PV, 41.1% ET, and 16.2% had MF at time of TTE, 48.5% were male and 86.8% were White race. PH was diagnosed in 195 patients (35.1%). The median time from MPN diagnosis to TTE was 39 months. Patients with PH were older (median age 71 vs 66 years, p <0.001), more likely to have MF (25.6% vs 11.1%, p <0.001), and higher VAF of driver MPN mutation (median 50% vs 40%, p = 0.002) and larger spleen sizes at time of TTE (median 13.7 vs 12.0 cm, p <0.001). Patients with PH had a higher rate of prior HF (15.4% vs 3.3%, p <0.001), hypertension (69.7% vs 56.7%, p= 0.003), and AF (29.7% vs 15.6%, p <0.001). After a median follow-up of 51 months, the composite hematologic outcome (23.6% vs 10.3%, p <0.001) and MACE (41.5% vs 19.2%, p <0.001) were more common among patients with PH. After multivariable competing-risk regression, PH was associated with increased risk of hematologic outcome (aSHR 1.79, 95% CI 1.10-2.92) and MACE (aSHR 1.67, 95% CI 1.10-2.56). Among patients with PH, 46 (23.6%) had hematologic outcome. After adjustment, atrial enlargement (aSHR 0.42, 95% CI 0.20-0.90) and valvular regurgitation (aSHR 0.30, 95% CI 0.16-0.57) were associated with decreased risk of hematologic outcome. Tricuspid annular plane systolic excursion (TAPSE, aSHR 2.44, 95% CI 1.27-4.69), a marker of right ventricular (RV) function, and estimated cardiac output (CO, aSHR 1.33, 95% CI 1.40-1.70) were associated with increased risk of hematologic outcome.
Conclusions:
Among patients with MPN, PH was associated with increased risk of hematologic progression and MACE. Our study also sheds some light on the pathophysiology behind PH and MPN progression given the association between preserved RV function and higher CO and MPN progression. MPN progression may lead to increased catabolic demand and cell turnover that may increase CO and may in part explain the association of preserved RV function and increased CO among patients with PH and MPN progression. However, further studies are needed to better understand the physiology of PH in MPN, characterize PH phenotypes and their associations with outcomes, and to assess the utility of TTE for screening for PH and surveillance of MPN progression.

 

Clinical Characteristics Defined in Adolescents and Young Adults With MPNs in Japan

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Vicki Moore, PhD

An analysis based in Japan identified differences in clinical characteristics between adolescents and young adults (AYA) and the non-AYA population among those with polycythemia vera (PV) or essential thrombocytopenia (ET). Findings were reported in the International Journal of Hematology.

The study was a large-scale retrospective analysis of AYA patients (aged 20 to 39 years) in the Japanese JSH-MPN-R18 registry who had been seen for an initial visit for PV or ET between April 2005 and March 2018. The study investigators evaluated clinical characteristics associated with PV or ET in this AYA cohort to increase understanding of myeloproliferative neoplasms (MPNS) in this population, in comparison with non-AYA patients from the registry.

In the registry, a total of 596 patients with PV and 1152 patients with ET were identified. There were 31 AYA patients among those with PV and 141 AYA patients among those with ET, corresponding to 5.2% of the total patients with PV and 12.2% of those with ET. In the AYA cohort, the median age at diagnosis was 33 years with PV and 32 years with ET.

AYA patients with PV had a lower median neutrophil ratio (71%) than non-AYA patients with PV did (78%; P <.01). Their median neutrophil count (6.5 x 109/L) was also lower than in the non-AYA population with PV (9.238 x 109/L; P =.03).

Among patients with ET, the AYA cohort showed lower values than non-AYA patients did for numerous parameters, such as median leukocyte count, neutrophil ratio, neutrophil count, lactate dehydrogenase level, and D-dimer level (P <.01 each). Palpable splenomegaly was also more common among AYA than non-AYA patients in the ET group (6.3% vs 2.3%, respectively; P =.02).

In patients with ET, the 5-year rate of hemorrhage-free survival (HFS) was higher for AYA patients (100%) than for non-AYA patients (93.9%; P <.01). For patients with PV, HFS did not significantly differ between AYA and non-AYA patients.

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