Managing Early Satiety in MPNs

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October 26, 2023

Alex Biese

Early satiety is one of the symptoms faced by patients with myeloproliferative neoplasms (MPNs) — a set of blood cancers that cause the bone marrow to overproduce red or white blood cells or platelets. Polycythemia vera, essential thrombocythemia and myelofibrosis are all MPNs.

“Early satiety means that you feel full really soon after you start eating,” explained Amanda Smith, a registered nurse at the Huntsman Cancer Institute at the University of Utah. “There are a lot of implications for this. Nutrition is a really big deal, especially when you have a blood disorder or a cancer, so it’s definitely something to be aware of.”

In an interview with Oncology Nursing News, Smith discussed the impact that early satiety can have on patients with MPNs and the role nurses playing in helping patients manage this symptom.

Oncology Nursing News: What kind of impact on quality of life and nutritional intake can this have on patients? And then how can both of those things affect patient outcomes overall?

Smith: If you are not able to eat, it can be really frustrating. Anyone who has ever had a short period of time where they have been unable to eat, knows how run down you can feel, and the lack of energy. You are not getting energy from food as you normally would. And so, it can compound with other things to make you feel just really extra run down. Nutrition is important for our immune systems and it can really have a spiraling effect if we cannot get it under control.

Part of the reason it happens in MPNs is because of splenomegaly, [which] is when your spleen is enlarged. That can happen for a few different reasons, but one of the jobs of the spleen is to filter the blood. When you have an MPN and you have too many platelets or other types of blood cells, then your spleen is — in the simplest terms— working so hard to try and filter all those cells, and it gets too big. Then there is just not room in your abdomen. There’s not enough room in there. That is why it happens.

Patients with MPNs can go through long asymptomatic periods, which is one of the things that makes MPNs really tricky to diagnose and manage. Can this early fullness be a warning sign for patients?

Yes. I know that our providers ask about it every time, so if it’s important enough that they are wanting to know if there have been any changes in that in that area, then yes. Some people can be very stable with this symptom for a long time. As with a lot of things in medicine, the important thing to watch out for is change. You can have a symptom, and it can be stable and may or may not be something to worry about. But if you’ve had an acute change—if something gets a lot worse—it’s definitely something that we would want to know about.

How can nurses help patients manage this issue with things like maximizing their nutritional intake?

The higher calorie foods that you can get down, we would encourage that. We’re also looking at electrolytes a lot, so we’re wanting to make sure those are balanced. High-protein, high-fat types of things, but also just things that you are able to eat. So, it can be really tricky.

A lot of our medications can help shrink the spleen, so medication adherence is huge. Often people feel so much better that they don’t need to be reminded, [but] it’s so critical to stay on the regimen that the doctor prescribes.

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Thromboembolic Events Characterized in Patients with MPNs

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October 26, 2023

By Patrick Daly

According to a single-center, retrospective analysis in Hämostaseologie, myeloproliferative neoplasm (MPN)-associated arterial thromboembolic events (ATEs) and venous thromboembolic events (VTEs) are frequent, and “while [polycythemia vera (PV)] patients or generally JAK2-mutated MPN patients had a significantly increased risk of such vascular events, this risk was reduced in CALR-mutated MPN patients.”

Lead author Kai Wille, MD, of the Johannes Wesling Medical Center Minden at the University of Bochum in Germany, wrote that patients with BCR–ABL-negative MPN frequently experience morbidity and mortality due to these events; however, few studies have reviewed both MPN-associated ATEs and VTEs across all MPN subtypes.

Uncontrolled MPN at Higher Risk of VTE, ATE

Among 892 patients with MPNs with a median follow-up of 6.6 years (range, 0.0-37.6 years), researchers identified 180 first TEs comprising 105 VTEs and 75 ATEs. The probability of an event by the end of the follow-up period was 36.2%, and the incidence rate for any first TE was 2.43% patient/year.

The most frequent VTE type was deep vein thrombosis with or without pulmonary embolism at a rate of 0.59% patient/year, and the most frequent ATE was stroke at a rate of 0.32% patient/year.

Between the 180 patients with a TE and the 652 without, patients with PV had a significantly increased risk of a TE (hazard ratio [HR], 1.660; 95% CI, 1.206-2.286) compared with other MPN subtypes. Conversely, CALR-mutated MPN had a significantly reduced risk of thromboembolism compared with JAK2-mutated MPN (HR, 0.346; 95% CI, 0.172-0.699).

“In summary, our study shows a significantly increased risk of VTE and ATE (often at “unusual” sites) in MPN patients compared with the healthy population, and this risk seems to be particularly increased in newly diagnosed and/or uncontrolled MPN.” Dr. Wille concluded.

Reference

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

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The Effects of Aging on Profiling Epigenetic Changes in Myeloproliferative Neoplasms

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October 24, 2023

Pearl Steinzor

Epigenetic changes in myeloproliferative neoplasms (MPNs) have been identified and characterized regarding the effects of aging and therapeutic pathways, according to a recent review. These changes help researchers understand how epigenetic changes affect patients with MPNs and the progression of this rare disease.

In the current study, researchers aimed to review the current knowledge and understanding of epigenetics in patients with MPNs to evaluate and improve management of the disease.

“Reversible epigenetic changes and epigenetic regulation are part of the pathogenesis of MPNs both in the disease development and in progression,” the researchers wrote. “Epigenetic changes in MPN have been investigated with a variety of results.”

Epigenetic changes are reversible modifications to chromatin structure, histone modifications, and DNA methylation, and they are responsible for how genes are either expressed or silenced. Alterations in these structures may result in downstream gene expression changes that may influence the initiation, maintenance, or progression of a malignant cell.

In MPNs, the 3 most common pathogenetic mutations identified were epigenetic regulators: TET2, ASXL1, and DNMT3A, which were present at frequencies above 5% in an unselected MPN patient population. Additionally, EZH2 occurred in approximately 2% of patients with MPN overall and appear particularly important in determining disease progression. The mutations affect the regulation of DNA histone methylation in the hemopoietic stem cell (HSC) compartment. Furthermore, ASXL1, EZH2, IDH1/2, and TET2 were implicated in the progression to fibrotic leukemic transformations and reduced survival.

Additionally, the researchers identified nuclear factor erythroid 2 (NFE2) as a transcription factor that was overexpressed in most patients with MPN. One study found insertions and deletions of NFE2 were described in approximately 2% of patients with MPN. Furthermore, NFE2 mutations were found to be a predictive variable in determining the risk of fibrotic transformation among a large cohort of patients with MPNs with chronic stage disease.

Most studies on DNA methylation have been conducted on a gene-by-gene basis, as well as in comprehensive methylation profiling studies. In a global DNA methylation study of patients with polycythemia vera, essential thrombocythemia, myelofibrosis, including some patients who had transformed to acute myeloid leukemia (AML), MPN samples showed an aberrant methylation pattern compared with control samples. However, samples were similar across the 3 disease types. Furthermore, patients with transformed AML had an increased number of differently methylated regions compared with chronic cases. Therefore, the researchers believe that altered DNA mutations may be associated with the pathogenesis of leukemic transformations in MPNs.

DNA methylation was found to be affected by aging, lifestyle, diet, and disease, so methylation age may be a more accurate describer of disease than chronological age. Studies have found an older methylation age in patients with a higher JAK2V617F allelic burden and in those with a longer disease duration. Patients with polycythemia vera had an older methylation age than predicted, but methylation age was younger than predicted in patients with essential thrombocythemia, which may be attributed to the mutant allele burden.

Additionally, treatment with vorinostat (Zolinza) resulted in younger methylation age in patients with polycythemia vera and an older methylation age in patients with essential thrombocythemia, contributing to an overall trend to normal chronological age. Furthermore, nonresponse to treatment was associated with a younger than predicted methylation age in patients with essential thrombocythemia and an older predicted age in patients with polycythemia vera.

Overall, the researchers believe that these studies show the effect of aging and treatment on the epigenetic changes in MPNs.

“However, there is room for much greater investigation and understanding of epigenetic changes and events involved in progression,” wrote the researchers. “Investigation of the epigenome shows that there are a variety of therapeutic pathways available and that can be explored further leading to targeted therapy.”

Reference

Greenfield G, McMullin MF. Epigenetics in myeloproliferative neoplasms. Front Oncol. 2023;13:1206965. doi:10.3389/fonc.2023.1206965

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MPN-Related Fatigue Has a ‘Profound Effect’ on Patients’ Quality of Life

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October 19, 2023

Patrick Buxton, RN, BSN

Patients with myeloproliferative neoplasms (MPNs) experience a number of symptoms—and fatigue is one of them, explains Patrick Buxton, RN, BSN.

MPNs are types of blood cancer and occurs when there is an abnormal change in stem cells within the bone marrow, according to the Leukemia and Lymphoma Society. This abnormal change can lead to increased amounts of white cells, red cells and platelets. The main three types of MPNs include essential thrombocythemia, myelofibrosis and polycythemia vera.

In an interview, Buxton, who is a clinical nurse coordinator with the hematology department at Fred Hutchinson Cancer Center, spoke with Oncology Nursing News about the symptom of fatigue that patients with MPNs often experience.

Oncology Nursing News: How does fatigue affect a patient’s quality of life?

Buxton: Fatigue has a profound effect on patients’ quality of life. A lot of people don’t realize that if you have chronic fatigue, especially from MPNs, it can actually be debilitating. They [may] not have the energy to go out and work, participate in family events and life in general. And they just don’t really feel well. Just overall.

It is important to monitor these patients’ labs to make sure that they stay within the range for their condition to ensure that they don’t end up developing those symptoms again, because when your blood counts become so high that your blood basically becomes a sludge, you definitely feel it.

Fatigue is a very subjective side effect. How do you try and understand the severity of an individual’s fatigue?

We ask questions of how it is interfering with their day-to-day life. Do they have the energy to go about their day? Do they need to take breaks and several naps? There was once a patient that had fatigue so bad, she could barely get out of bed in the day. We were able to help get her condition under control, and then she was able to get back to her life. It was very hard for her to be in bed because she had 2 small kids.

We were able to kind of dial in her disease and get her started on a medication regimen. She was able to tell with actually her levels of fatigue how her blood counts were doing. She could tell when they were starting to creep up a bit. And we would address her adjust her medication based on labs. But sometimes she would call and say ‘Hey, could I get my labs a couple weeks early? Because I’m noticing my symptoms are starting to come back up a little bit.’ She would be very proactive about trying to keep that under control.

What are some ways a nurse can help patients work through and control fatigue?

A lot of it is to assess how it is affecting their daily life. Sometimes fatigue can also bleed into other things; it is hard to differentiate. Especially with MPNs, [ensuring that] patients maintain good hydration and adequate nutrition is very important. Because once you kind of get stuck in a downward spiral, it can be very hard to get out. Making sure that you educate patients and making sure that they are trying to get a good amount of exercise daily—even if it’s just getting out of bed, pushing yourself a little bit each day to try to get that energy going again, and making sure that you eat and drink enough to keep going [is important].

Hydration cannot be stressed enough, a lot of people don’t hydrate with water, as I have come to realize, and so there’s been a lot of education of patients have like, ‘Oh, I drink all the soda.’ And I’m like, ‘That’s not really helping. You need to drink water, especially when you have this condition, you need to keep on top of things.’

What advice would you offer other nurses who work with patients with MPNs?

Build up that trust with those patients. Have the patient trust that you will take their symptoms seriously when they report them to you.

A lot of patients don’t necessarily like to open up — to say, just the nurse — about their fatigue. But if they are not necessarily within a short distance of your clinic—we have a lot of patients that are in eastern Washington—establishing that line of connection, can be key. Just being like, ‘Hey, let us know, even if you don’t think it’s important,’ ‘Let us know because you don’t know if it’s a sign of something greater, you know your own body.’ And ‘You can tell us when something’s not right, we can always do labs and see. And based on those results, maybe we might do a medication change.’ We might tell you to follow up with your primary care, but we’ll always do something with those lab results.

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Azacitidine, Venetoclax, Ruxolitinib Shows Encouraging Responses in MPNs

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October 19, 2023

Sabrina Serani

The combination of azacitidine, venetoclax (Venclexta), andruxolitinib(Jakafi) for the treatment of myeloproliferative neoplasms in blastic phase (MPN-BP) did not demonstrate any treatment-related toxicity in patients, and patients’ quality-of-life improved, according to a study published in the British Journal of Haematology.1

Azacitidine and venetoclax were used to control BP transformation, and ruxolitinib was added to control constitutional symptoms. The overall response rate was 80%, and the complete remission (CR) rate was 40%. The median overall survival was 13.4 months (95% CI, 4.2-13.4), with a median follow-up of 10.0 months (range, 4.2-13.4).

“[Patients with] MPN-BP have a poor prognosis with the current treatment options, and standards of care unless they are offered [allogeneic stem cell transplant, (allo-SCT)]. Unfortunately, there is a lack of treatment guidelines for the management of allo-SCT-ineligible MPN-BP patients,” study authors wrote. “We observed encouraging hematological responses, which were prolonged for some patients. In addition, the combination appeared manageable, without unexpected adverse events.”

Five patients with myelofibrosis (MF) were enrolled in the study. One had primary MF, and 4 had secondary MF. The median patient age was 76 (range, 72-84) years. Three patients were treated exclusively outpatient. There were 2 CRs and 2 partial response remissions. Investigators noted that all patients could complete their activities of daily living, and clinical spleen reduction ≥50% was observed.

At best response, the median platelet count was 150 × 109/L (range, 60–380) with a median improvement of 125 × 109/L (range, 5–200), and median hemoglobin level was 10.6 g/dL (range, 9.0–13.8) with a median gain of 2.7 g/dL (range, 1.5–7.6).

Three patients died due to disease progression; however, there were no deaths due to treatment reported. Observed adverse events (AEs) included neutropenia (n = 4, 80%), anemia (n = 2, 40%), and thrombocytopenia (n = 1, 20%). Febrile neutropenia was reported in 2 patients during the initial cycle. Grade 4 neutropenia was the primary reason reported for postponing a cycle.

Patients were administered ruxolitinib and a dose ≥10 mg twice daily. Venetoclax was administered orally at a dose of 200-400 mg on days 1-14. Azacitidine was administered subcutaneously at a dose of 50 or 75 mg/m2 on days 1-7. The median cycle duration was 29 days (range, 27-38). A median of 11 cycles (range, 5-14) was administered to patients, and the median time to best response was 4 cycles (range, 3-9).

“Further studies are needed to confirm these promising results,” study authors wrote.1

The combination of venetoclax and azacitidine are also being studied in a phase 3 trial of patients with treatment-naïve acute myeloid leukemia, as well as a phase 1 trial of pediatric and young adult patients with hematologic malignancies.2,3

REFERENCES:
1. Systchenko T, Chomel JC, Gallego-Hernanz P, et al. Combination of azacitidine, venetoclax and ruxolitinib in blast phase myeloproliferative neoplasms. Br J Haematol. 2023;202(2):284-288. doi:10.1111/bjh.18853
2. A study of venetoclax in combination with azacytidine versus azacytidine in treatment naïve participants with acute myeloid leukemia who are ineligible for standard induction therapy. News release.National Cancer Institute. Accessed October 13, 2023. https://tinyurl.com/my5yh7nm
3. Venetoclax and azacytidine for the treatment of hematologic malignancies in pediatric and young adult patients. News release. National Cancer Institute. Accessed October 13, 2023. https://tinyurl.com/my5yh7nm

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Newer-Generation JAK Inhibitors Expand Myelofibrosis Treatment Paradigm

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October 19, 2023

Ashling Wahner

The growing array of JAK inhibitors available to patients with myelofibrosis underscores the need for personalized treatment decisions in this patient population, which may depend on baseline cytopenias, disease characteristics, and the availability of second-line options for patients who progress on first-line ruxolitinib (Jakafi), according to Anthony M. Hunter, MD.

The pivotal phase 3 PERSIST-2 trial (NCT02055781) showed that 29% patients who received pacritinib (Vonjo) achieved a spleen volume reduction of at least 35% compared with 3% of those who received best available therapy, which included ruxolitinib.1 Additionally, momelotinib (Ojjaara), which was approved by the FDA in September 2023 for adult patients with intermediate- or high-risk primary or secondary myelofibrosis and anemia, is the newest JAK inhibitor to be approved for patients in this population.2

“Instead of just giving everybody the same treatment no matter what, we have room to pick and choose who will be a better [candidate] for which drug,” Hunter said in an interview with OncLive® during the 2023 SOHO Annual Meeting.

In the interview, Hunter discussed the roles for pacritinib, momelotinib, and fedratinib (Inrebic) in patients with myelofibrosis; treatment sequencing with newer-generation JAK inhibitors after ruxolitinib; and the importance of having several treatment options in the second-line setting and beyond.

Hunter is an assistant professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine, and medical director of the Immediate Care Center at Winship Cancer Institute of Emory University, both in Atlanta, Georgia.

OncLive: What was the goal of your presentation on choosing and properly using JAK inhibitors in myelofibrosis?

Hunter: The goal [of my presentation] was to discuss the historical and emerging data with JAK inhibitors. We’ve had JAK inhibitors around for approximately 12 years, from the first one, ruxolitinib, but now, [we are] starting to see an increase in that arsenal, and our fourth JAK inhibitor, [momelotinib, was] approved [in September 2023].The goal was to review the data with these different JAK inhibitors we have already available or emerging right now; discuss some of the unique differences between them and where they may fit into specific subgroups of patients; and [discuss] the practical standpoints of how to use these drugs in clinical practice.

Considering the number of JAK inhibitors that are available, what factors guide your treatment decisions?

[We consider several factors] right now. One of the biggest factors we see that distinguishes a couple of the different JAK inhibitors is patients who have low blood counts or cytopenias at baseline. Standard patients with more elevated counts, or at least not significant cytopenias, are still using ruxolitinib, and we have fedratinib as well.

However, cytopenic patients who historically have been a tough group to treat with our original JAK inhibitors, now have some emerging options. Pacritinib is for patients with lower platelet counts, platelet counts of less than 50 x 109/L, who have historically been excluded [from treatment with JAK inhibitors]. In addition, [data are] showing that [pacritinib] has the potential [to improve] anemia as well. Additionally, momelotinib, [which was approved by the FDA in September 2023, is] an active agent in the setting of these anemic patients, with the potential to improve outcomes.

One of the biggest factors for choosing between these options is the presence of baseline cytopenias. All [these agents] show good activity in the settings of spleen responses and symptom reductions. [We don’t have a lot of] clear data about which subgroups of patients, aside from cytopenic patients in the front line, we should switch between [JAK inhibitors]. Otherwise, the rest of these [agents] are certainly options still. Then, certainly in the second-line setting, we have data with pacritinib, momelotinib, and fedratinib all having some activity after progression on ruxolitinib.

How might the use of pacritinib expand to benefit patients with higher platelet counts?

The National Comprehensive Cancer Network Guidelines for Myeloproliferative Neoplasms have been updated and have included pacritinib as an option for patients with a platelet count of over 50 x 109/L. In more anemic patients, we see anemia responses with pacritinib, so it has a role in that population. A sometimes tougher group is patients with a platelet count between 50 x 109/L and 100 x 109/L, who are able to use drugs like ruxolitinib or fedratinib.

When we start to see thrombocytopenia develop on treatment, [these agents may] start to hit those low platelet levels as well. It’s hard to maintain continuous and effective dosing with some of these patients. Even in patients with more modest levels of thrombocytopenia, there may be some role for pacritinib.

How are JAK inhibitors currently sequenced after ruxolitinib in the first-line setting?

We have seen with ruxolitinib, in multiple real-world cohorts and clinical trials, that outcomes once patients have progressed on ruxolitinib, whether that be [because of] intolerance or resistance to treatment, are quite poor, with survival in the 12- to 16-month range in most studies. Historically, there have not been great data about how to treat these patients. Studies suggest that novel agents, which have included second-line JAK inhibitors, have shown more promise than conventional agents like hydroxycarbamide. The [phase 3] MOMENTUM [NCT04173494] and SIMPLIFY 2 [NCT02101268] studies with momelotinib, PERSIST-2 and other studies with pacritinib, and the [phase 2] JAKARTA-2 study [NCT01523171] with fedratinib are all clinical trials that investigated these agents in patients who had previously been exposed, or at least included patients who had been exposed, to prior ruxolitinib.

We see activity with all those different agents. More advanced patients potentially get more cytopenias and anemias. Some of these newer agents that are a bit more designed for that patient population may have a bigger role there, but certainly fedratinib has also [been associated with] great data in the second-line setting in this population.

What is your main message for colleagues regarding the use of JAK inhibitors in myelofibrosis?

We have options now. For a long time, we only had 1 agent, for the most part. We’ve now had a couple more approved in the past few years, so we’re starting to get to a point now where we can pick and choose a little. We can match [treatments] to clinical features, like cytopenias, potentially, as well as comorbidities and other disease- or non-disease–related aspects that will give us more leeway to treat patients more effectively in a more personalized approach. Also, [there is the] potential to sequence these options, so we have more effective options for patients who progress on first-line treatment.

References

  1. CTI BioPharma announces FDA accelerated approval of VONJO (pacritinib) for the treatment of adult patients with myelofibrosis and thrombocytopenia. CTI BioPharma Corp. News release. February 28, 2022. Accessed October 2, 2023. https://www.prnewswire.com/news-releases/cti-biopharma-announces-fda-accelerated-approval-of-vonjo-pacritinib-for-the-treatment-of-adult-patients-with-myelofibrosis-and-thrombocytopenia-301492159.html
  2. Ojjaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anaemia. News release. GlaxoSmithKline. September 15, 2023. Accessed October 2, 2023. https://www.gsk.com/en-gb/media/press-releases/ojjaara-momelotinib-approved-in-the-us-as-the-first-and-only-treatment-indicated-for-myelofibrosis-patients-with-anaemia

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Statin Use and Outcomes With Polycythemia Vera or Essential Thrombocythemia

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October 19, 2023

Vicki Moore, PhD

In patients with polycythemia vera (PV) or essential thrombocythemia (ET), researchers found that statin therapy was associated with possible benefits related to survival and thrombosis in a new study. The researchers reported their findings in the journal Cancer Medicine.

In this cohort analysis, the researchers evaluated data on statin use and outcomes for 4010 adults with PV or ET who were of age 66 through 99 years at diagnosis and who were identified through the Surveillance, Epidemiology, and End Results-Medicare database.

The researchers analyzed patients in 2 cohorts, based on using either propensity score matching (PSM) or inverse probability of treatment weighting (IPTW), to evaluate possible relationships between statin use and outcomes. Cox proportional hazards analyses were performed to evaluate outcomes related to survival and first incident thrombotic events. The median follow-up time was 3.92 years.

The study included 1809 patients with PV and 2201 patients with ET. Patients had a median age at diagnosis of 77 years in both the PV and ET subgroups. In the first year after being diagnosed with PV or ET, over half (55.8%) of the patients overall had used statins.

For patients with PV, with a median follow-up of 4.00 years, 35.0% of those who used statins had died whereas 43.0% of patients not using statins had died. Among patients with ET, at a median follow-up of 3.84 years, deaths were reported among 35.7% of those who used statins and in 40.9% of those who did not use statins. A sensitivity analysis suggested that survival differences with statin use were significant for patients who had not been receiving statin therapy prior to their PV or ET diagnosis.

Statin use also was associated with a lower risk of thrombosis across the overall study population. In the PSM cohort, the HR was 0.63 (95% CI, 0.51-0.78; P <.01) for this association, and in the IPTW cohort, the HR was 0.57 (95% CI, 0.49-0.66; P <.01). A lower risk of thrombosis with statin use was also observed in PV and ET subgroups.

“Overall, our study demonstrated that statins improved survival and decreased the incidence of thrombotic events in older patients with PV and ET,” the researchers wrote in their report.

Reference

Podoltsev NA, Wang R, Shallis RM, et al. Statin use, survival and incidence of thrombosis among older patients with polycythemia vera and essential thrombocythemia. Cancer Med. Published online September 13, 2023. doi:10.1002/cam4.6528

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Dr Kuykendall on Frontline Cytoreductive Therapies in Polycythemia Vera

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October 20, 2023

Andrew Kuykendall, MD

Andrew Kuykendall, MD, assistant member, Department of Malignant Hematology, Moffitt Cancer Center, discusses frontline cytoreductive treatment options for patients with polycythemia vera.

In the management of polycythemia vera, the choice of treatment with frontline cytoreductive therapies is primarily between pegylated interferon alfa-2a or hydroxyurea, 2 agents that possess distinct characteristics, Kuykendall says. Pegylated interferon alfa-2a is administered subcutaneously and provides long-acting efficacy, whereas hydroxyurea is an oral agent with a shorter duration of action, Kuykendall explains. Additionally, although both agents are relatively well tolerated, their adverse event profiles differ from one another and inform the use of these agents in different patient populations, Kuykendall notes.

For instance, older patients with polycythemia vera typically receive hydroxyurea, whereas younger patients will often receive pegylated interferon alfa-2a, according to Kuykendall. Although both agents are reasonable frontline treatment options for patients with polycythemia vera, the rationales for the use of each agent differs, Kuykendall emphasizes.

A randomized phase 3 trial compared pegylated interferon alfa-2 vs hydroxyurea in patients with polycythemia vera and essential thrombocytopenia. In the patients with polycythemia vera, the 12-month complete response (CR) rates with pegylated interferon alfa-2 and hydroxyurea were 28% and 30%, respectively (P = .80). At 24 months, the CR rates were 25% with pegylated interferon alfa-2 and 17% with hydroxyurea. At 36 months, the CR rates with pegylated interferon alfa-2 and hydroxyurea were 29% and 17%, respectively. Additionally, of the patients who received post-baseline imaging for spleen response, the median spleen reduction was –6% (best response on treatment range, –37% to 54%) with pegylated interferon alfa-2 vs –5% (best response on treatment range, –24% to 17%) with hydroxyurea.

The use of pegylated interferon alfa-2 has increased over the past few years because of ongoing developments with this agent, including the advent of more tolerable formulations and its potential to elicit long-term disease modification, Kuykendall explains. This growing inclination toward using pegylated interferon alfa-2 underscores the ongoing interest in finding polycythemia vera treatments that can do more than simply reduce thrombotic potential for patients, Kuykendall says.

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Hydration and Movement Are Important for Patients With MPNs

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October 18, 2023

Alex Biese

Patients with myeloproliferative neoplasms (MPNs) — a group of blood cancers that causes the bone marrow to overproducer red or white blood cells or platelets and which includes polycythemia vera, essential thrombocythemia and myelofibrosis) — are at particular risk for thrombotic and cardiovascular events.

“It’s really a problem for all patients with cancer because it does increase your chances of developing a clot, for example,” said Kim Noonan, nursing and patient care services chief nurse practitioner at the Dana-Farber Cancer Institute in Boston, during a conversation about the risks faced by patients, and the ways in which nurses can help patients prevent cardiovascular and thrombotic events.

However, such risks are of particular concern for patients with MPNs, as literature has shown.

“Clinicians have long recognized an association between MPNs and increased risk for both thrombotic and hemorrhagic complications,” stated the authors of an article published in JACC: CardioOncology. “A recent meta-analysis of 13,436 patients with MPNs showed a pooled prevalence of arterial thrombosis of 16.2% and of hemorrhagic complications of 6.2%. Indeed, cardiovascular events often accompany this cluster of hematologic conditions and contribute significantly to morbidity and mortality.”

Symptoms of a clot or pulmonary embolus include shortness of breath and chest pain, especially following exertion, as well as an elevated or irregular heart rate and an unexplained fever noted Noonan, the co-author of a Journal of Oncology Nursing study on the assessment and prevention of venous thromboembolism and cardiovascular disease among patients with another form of blood cancer, multiple myeloma.

“I’m always thinking about thrombosis first, and then I can relax if I have maybe another explanation for their shortness of breath,” Noonan said. “But we’re always working it up, we really do due diligence to not miss some kind of thrombotic event that’s going on.”

Transcript:
I think when people see me, they just feel like they have to start jogging, because I’m always saying, “You (have) got to move, you have to move, you have to move.” And it’s so, so important. That person that is sedentary is really at a huge risk to the point of where if they have a sedentary lifestyle, we’re thinking maybe that person needs to be on needs to be on anticoagulant therapy right from the beginning, as opposed to just using an aspirin.

We really want people to stay hydrated. We want them to get up and walk around. We want them to be aware of what the symptoms are (and be aware that) they can be doing everything right and still develop a clot because of the medication that they’re on. But I think also, education is essential, (letting a patient know) that you are on a medication that can increase your chances of developing a clot or thrombosis, and (you should) just be aware of what the symptoms are.

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Advancing the Treatment Landscape for Patients With Myeloproliferative Neoplasms

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Pearl Steinzor

Despite recent advancements in treatments for patients with myeloproliferative neoplasms, a term encompassing several rare cancers, many challenges persist when it comes to these hematologic malignancies, primarily due to lack of uniform treatment plans for each of the classical subgroups.

These findings were presented in a landscape analysis by the Association of Community Cancer Centers (ACCC) at the 2023 National Oncology Conference from October 4-6, 2023, in Austin, Texas.

In 2008, the World Health Organization (WHO) reclassified myeloproliferative disease from a blood disorder to clonal hematopoietic stem cell malignancies, and in 2016, the WHO identified 4 classic types of myeloproliferative neoplasms: chronic myeloid leukemia (BCR-ABL1 positive), polycythemia vera (BCR-ABL1 negative), essential thrombocythemia (BCR-ABL1 negative), and primary myelofibrosis (ABCR-ABL1 negative).

Patients with myeloproliferative neoplasms report debilitating symptoms, including fevers, night sweats, fatigue, sleep disturbances, weight loss, bone pain, itchy skin, headaches, difficulty concentrating, anxiety, and depressive symptoms.

Although these patients are considered to have favorable life expectancy, with 60% of patients living up to 15 years after diagnosis, about 84% of these patients have reported a reduced quality of life directly due to these symptoms. Moreover, many low-risk patients are given a “watch-and-wait” treatment plan and receive no drug therapy despite experiencing a moderate to high symptom burden.

Gaps in care coordination also exist, and current standard-of-care pharmacological treatments are unable to fully relieve symptom burden. For example, approximately 84% of patients with myeloproliferative neoplasms reported reduced quality of life due to the effects of their current pharmacological interventions.

Moreover, patient and physicians perceptions regarding treatment are often misaligned, with patients reporting that their most important treatment goal was to slow or delay disease progression, whereas physicians reported the most important goal was symptom improvement and prevention of vascular or thrombotic events. Furthermore, an average of 30% of patients with myeloproliferative neoplasms did not believe their physician had a treatment plan, and an average of 35% of patients believed their physician was not providing updates on new treatments.

The researchers also identified health literacy as an important factor in understanding and managing symptom burdens, shared decision-making, and proper disease management. Additionally, a 2016 online survey of 904 adults found significant employment disruptions were common, with at least 1 employment change reported among 65.5% of patients with myelofibrosis, 48% of patients with polycythemia vera, and 38.8% of patients with essential thrombocythemia. Furthermore, respondents reported reduced working hours, medical disability leave, early retirement, dropping to part-time hours, and switching to a lower-paying job due to their disease.

For these reasons, myeloproliferative neoplasms have a significant disease burden and impact on patients, commonly due to anxieties about disease advancement and disruptive symptoms that affect a person’s quality of life.

Furthermore, lack of uniform treatment, risk diagnostic assessments, and care coordination can result in late diagnosis and rapid potential disease progression, which may also lead to a lack of transparency and patients feeling excluded in decision-making of their care.

Moreover, a lack of awareness surrounding available care guidelines, standardized symptom alleviation, and disease progression control plans are stressors that add to this disease burden, so further knowledge on the management of myeloproliferative neoplasms and related symptoms is necessary to improve patient outcomes.

Reference

Advancing care for patients with myeloproliferative neoplasms. Association of Community Cancer Centers. Accessed October 17, 2023. https://www.accc-cancer.org/home/learn/cancer-types/hematologic-malignancies/advancing-care-for-patients-with-myeloproliferative-neoplasms.

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