Category Archives: Blood Cancer

Bomedemstat as an investigative treatment for myeloproliferative neoplasms

Posted on by

By Hugh Young Rienhoff Jr. & Harinder Gill

Abstract

Introduction

Myeloproliferative neoplasm (MPN) is a heterogeneous group of hematopoietic stem cell disorders characterized by clonal proliferation of one of more of the hematopoietic stem cell lineages. Clinical manifestations result from uncontrolled myeloproliferation, extramedullary hematopoiesis with splenomegaly and excessive inflammatory cytokine production. Currently available therapy improves hematologic parameters and symptoms but does not adequately address the underlying neoplastic biology. Bomedemstat has thus far demonstrated clinical efficacy and tolerability in the treatment of MPNs with recent evidence of impacting the malignant stem cell population.

Areas covered

This review summarizes the mechanisms of action, pharmacokinetics and pharmacodynamics, safety and efficacy of bomedemstat in MPN with specific emphasis on essential thrombocythemia (ET) and myelofibrosis (MF).

Expert opinion

In patients with MPNs, bomedemstat appears effective and well tolerated. The signs and symptoms of these diseases are managed as a reduction in the frequency of mutant cells was demonstrated in patients with ET and MF. Ongoing and planned studies of bomedemstat in MPN will establish the position of bomedemstat in MPNs and may help to redefine treatment endpoints of MPNs in the future.

KEYWORDS:

  • Bomedemstat
  • lysine-specific demethylase-1
  • LSD1
  • myeloproliferative neoplasm
  • polycythemia vera
  • essential thrombocythemia
  • myelofibrosis

Article highlights

  • Myeloproliferative neoplasm (MPN) are clonal hematopoietic stem cell disorders characterized by uncontrolled cellular proliferation, cytokine mediated symptoms and clonal instabilty leading to leukemic progression.

  • Conventional therapeutic approaches in MPN are not adequate in altering the underlying disease biology.

  • Lysine specific demethylase 1 (LSD1) is overexpressed in the malignant hematopoietic stem cell population in MPN.

  • Bomedemstat, an inihibitor of MPN, effectively controls cellular proliferation and reverses disease biology in mouse models of MPN.

  • Phase 2 studies in essential thrombocythemia and myelofibrosis has demonstrated that Bomedemstat is highly efficacious and safe.

Declarations of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Read more

Blood Cancer Symptoms That Shouldn’t Be Ignored: Early Warning Signs and Diagnosis

Posted on by

Published on October 9, 2023

By Dr. Suraj D Chiraniya, Clinical Hematologist,  Hemato-oncologist and BMT Physician, HCG Cancer Centre, Borivali

A type of cancer that affects the blood cells. Some common types of blood cancer include leukaemia, lymphoma, and myeloma. Though rare, Myelodysplastic Syndromes (MDS) and Myeloproliferative Neoplasms (MPN) are some other types of blood cancer.

Caused by mutations in DNA within the blood cells, blood cancer results in blood cells behaving abnormally. Treatment, symptoms, and prognosis will vary depending on the type of blood cancer. Further, some types of blood cancer affect children, for which treatment can vary.

Understanding The Various Types Of Blood Cancer

One of the most common types of blood cancer affecting most blood cancer patients is leukaemia, defined as cancer of the blood cells. There are three main categories of blood cells: Red Blood Cells (RBC), White Blood Cells (WBC) and platelets. Leukaemia affects the WBC within the bloodstream and causes them to divide rapidly and eventually crowd out the normal cells. As a result of this, the WBC is unable to perform its function of fighting infections within the human body.

Lymphoma is another type of blood cancer that affects the human immune system. It specifically affects white blood cells called lymphocytes, a vital part of the immune system. Lymphoma can also be called a cancer of the lymphatic system or lymphatic cancer.

In general, there are two main types of lymphoma, namely Hodgkin lymphoma and non-Hodgkin lymphoma, which both affect the blood’s lymphocytes.

The third most common type of blood cancer is myeloma, which affects the blood’s plasma cells. Plasma cells help fight infections in the body, and when a person has myeloma, the body cannot make these antibodies properly. Additionally, abnormal cells multiply in this situation, causing various symptoms.

The majority of the people diagnosed with myeloma are men over the age of 70, although cases of it occurring in young men are also possible.

Who is at risk for blood cancer?

Although there are no specific conditions for blood cancer, the risk can sometimes increase with age. Further, a family history of this disease can also increase the risk.

In addition to the above, the risk of leukaemia can also increase due to the following factors:

•            exposure to radiation

•            treatment with certain chemotherapy drugs

•            a past diagnosis of blood cancer

•            Down syndrome and other genetic syndromes

•            Smoking

Risk factors for lymphoma, on the other hand, include the following:

•            exposure to radiation

•            Epstein-Barr or human T-cell lymphotropic virus

•            HIV, organ transplant, or genetic immune disorders

Some risk factors for myeloma include exposure to radiation, obesity, and other plasma cell diseases.

What are some common signs and symptoms of blood cancers?

Since blood cancer is a chronic condition that progresses slowly, symptoms may not appear until the end stage. While coughing, chest pain, frequent infections, fever and unexplained weight loss can occur in all the types of blood cancer, other symptoms may be specific to the condition.

Some symptoms of leukaemia include fever and lethargy, paleness and shortness of breath due to anaemia and increased bruising and bleeding. When it comes to lymphoma, symptoms may include swollen lymph nodes, fever, night sweats and fatigue and unexplained weight loss. Finally, in the case of myeloma, specific signs may include bone pain, particularly in the back and ribs, weakness, fatigue, and paleness due to anaemia and frequent bacterial infections, such as pneumonia.

Can blood cancer be prevented?

While there is no way to prevent blood cancer completely, certain lifestyle factors can reduce the risk of developing cancer. These include maintaining a healthy diet, exercising regularly, and not indulging in habits like smoking and excessive alcohol consumption.

Preventive health check-ups are highly recommended, especially if a person has a personal or family history of blood cancer, previous sessions of radiation therapy/chemotherapy or radiation exposure. If a person has experienced any symptoms related to blood cancer, it is best to consult an expert, as early diagnosis can ensure the best possible outcome.

Read more

Novartis makes sculptures to shape knowledge of cancer symptoms

Posted on by

By Nick Paul Taylor

September 18, 2023

Novartis has enlisted artists to help raise awareness of rare blood cancers, commissioning sculptures that portray the 10 key symptoms of the conditions to create a temporary exhibition that will tour the U.K.

The art exhibition is focused on symptoms of myeloproliferative neoplasms (MPN), a group of rare blood cancers that affect around 4,100 people in the U.K. each year. Novartis sells Jakavi for the treatment of MPNs in the U.K., recently securing coverage for one of the three main types of the blood cancer, and wants to spread knowledge that enables more cases to be identified early.

MPNs cause symptoms, such as fatigue, loss of concentration and night sweats, that overlap with other conditions, leading to delayed diagnoses. Novartis wants to bump MPNs up the list of potential causes that patients and physicians consider when they encounter the symptoms.

“More needs to be done to recognize and identify these symptoms early so that people living with the condition can seek help from medical professionals to better manage their symptoms, and those who are undiagnosed can seek a potential diagnosis sooner,” Alisia O’Sullivan, a MPN patient and MPN Voice volunteer, said in a statement.

To support that goal, the Swiss drugmaker has identified 10 key symptoms and commissioned sculptures to represent each of them. Each sculpture is in the shape of the number assigned to the symptom and features art that portrays the symptom. For example, symptom two, inactivity, displays a painting of someone sleeping under a blue sky and symptom three, weight loss, features a quote about being thin.

Novartis worked with MPN Voice and five mural artists from around the U.K. to create the sculptures and began showing them at Westfield, a shopping center in London, last week. The art exhibition will run for one week at Westfield and then go on a tour of U.K. cities.

Encouraging people to consider MPNs as an explanation for the 10 symptoms could support growth products for the condition. Novartis’ sales of Jakavi increased by 11%, rising to $435 million, in the second quarter on the back of demand in emerging markets, Japan and Europe.

Read more

Inflammation and the Development of Leukemia Are Connected

Posted on by

Penny Min

Published September 15, 2023

In blood stem cells with p53 mutations — the so-called “guardian of the genome” — research has uncovered hitherto unrecognized impacts of persistent inflammation on the emergence of cancer.

The protein p53, generated by the gene TP53, is regarded as “the guardian of the genome,” according to research published in Nature Genetics. Apoptosis, a process by which cells “self-destruct” to stop themselves from procreating additional damaged cells, is triggered when p53 is activated. However, mutations can make p53 ineffective, which allows injured cells to continue dividing unchecked.

As many as 50% to 60% of human malignancies have a TP53 mutation, which can result in cancer development. Hematopoietic stem cells (HSCs) with TP53 mutations have been associated with acute myeloid leukemia (AML), an aggressive kind of blood cancer.

By creating all different types of blood cells, they are in charge of preserving a healthy blood system. The processes behind how these mutant HSCs multiply to produce cancer were largely unknown. In the current study, researchers from the University of Oxford examined how chronic inflammation affects TP53-mutant HSCs in cancer development.

The study team used TARGET-seq, a single-cell method, to examine the impact of the mutation. This enabled them to use cells provided by individuals with myeloproliferative neoplasms, a condition that predisposes them to leukemia, to explore how TP53 mutations in HSCs impact cancer progression.

What did the results entail?

Researchers discovered that cells from individuals with TP53 mutations exhibited higher levels of inflammation-related gene activation. They established, using laboratory mice, that these mutant cells multiplied when the animals were exposed to inflammatory stimuli.

Additionally, compared to healthy HSCs, the mutant HSCs generated fewer white blood cells and were more resistant to cell death, which is normally brought on by inflammation. This indicates that compared to non-mutant HSCs, the mutated HSCs were better able to grow when exposed to inflammation and were more “fit” to survive.

The inability of TP53-mutated cells to effectively repair mistakes in their genetic coding when subjected to inflammation may exacerbate this impact and aid in cancer growth.

“Overall, these findings offer valuable insights into how genetic defects and inflammation interact in the development of blood cancer.”

– Co-first author Alba Rodriguez-Meira

Additionally, she continues that this research may lead to novel approaches for TP53-mutant leukemia therapy and other cancer types, improving results for cancer patients.

The connection between inflammation and genetic evolution in cancer has broad implications, says senior author Adam Mead. The challenge is to figure out how scientists might intervene in this process to treat or prevent the inflammation linked to cancer progression more effectively.

Read more

PharmaEssentia and MPN Advocacy & Education International Launch New Educational Initiative to Empower People Living With Polycythemia Vera (PV)

Posted on by

PV&ME™ campaign features personal stories from people living with PV and their journeys navigating the rare blood cancer

BURLINGTON, Mass. & EAST LANSING, Mich.–(BUSINESS WIRE)–PharmaEssentia USA Corporation, a subsidiary of PharmaEssentia Corporation (TPEx:6446), a global biopharmaceutical innovator based in Taiwan leveraging deep expertise and proven scientific principles to deliver new biologics in hematology and oncology, and MPN Advocacy & Education International, a leading advocacy group dedicated to providing the knowledge, support and resources patients will need as they adjust to living with a myeloproliferative neoplasm (MPN), today announced a new educational initiative for the MPN community called PV&ME. The goal of the campaign is to bring to light the unique and challenging experiences of living with polycythemia vera (PV) in the hopes of raising awareness, empowering patients to advocate for themselves and ensuring newly diagnosed patients feel supported in their journeys. PV&ME features the stories of four inspiring individuals – Buzz, Deb, Patti and Steven – living with this chronic cancer and their perspectives on navigating diagnosis, addressing burdensome symptoms and seeking comprehensive care.

PV is the most common MPN and a long-term, potentially life-threatening cancer that has had limited treatment options for many years. Patients with PV are at a more significant increased risk of developing thromboembolic events than the general population with cardiovascular disease, due to increased blood cell counts. They also have a long-term risk of progression to myelofibrosis or transformation to acute myeloid leukemia.1-5

“People living with PV often face feelings of isolation as they navigate a long and confusing road to diagnosis and adjust to extreme fatigue or other often debilitating symptoms,” said Ann Brazeau, Chief Executive Officer, MPN Advocacy & Education International. “The stories shared in this new PV&ME campaign show just how important the right support and resources can be for this community. We hope this new initiative will help people with PV feel connected and empowered to advocate for themselves on their PV journeys.”

“At PharmaEssentia, we are committed to being an essential partner for the MPN community and know that a critical component of that is listening to and amplifying stories from individuals living with PV themselves,” said Raymond Urbanski, M.D., Ph.D., Senior Vice President and U.S. Head of Clinical Development and Medical Affairs at PharmaEssentia. “This MPN Awareness Day, we are proud to partner with MPN Advocacy & Education International to share these inspiring stories with the MPN community and help encourage patients to take a proactive approach in their care.”

The PV&ME educational video series launched on MPN Awareness Day (September 14) and can be found by visiting us.pharmaessentia.com/patients/patient-stories/. Throughout Blood Cancer Awareness Month, PharmaEssentia and MPN Advocacy & Education International will continue to share important educational content for the MPN community.

Follow PharmaEssentia USA on Twitter and LinkedIn for news and updates.

About Polycythemia Vera (PV)

Polycythemia vera (PV) is a cancer originating from a disease-initiating stem cell in the bone marrow resulting in a chronic increase of red blood cells, white blood cells, and platelets. PV may result in cardiovascular complications such as thrombosis and embolism, and often transforms to secondary myelofibrosis or leukemia. While the molecular mechanism underlying PV is still subject of intense research, current results point to a set of acquired mutations, the most important being a mutant form of JAK2.6

About PharmaEssentia

PharmaEssentia (TPEx: 6446), headquartered in Taipei, Taiwan, is a global and rapidly growing biopharmaceutical innovator. Leveraging deep expertise and proven scientific principles, PharmaEssentia aims to deliver effective new biologics for challenging diseases in the areas of hematology and oncology, with one approved product and a diversifying pipeline. Founded in 2003 by a team of Taiwanese-American executives and renowned scientists from U.S. biotechnology and pharmaceutical companies, today PharmaEssentia is expanding its global presence with operations in the U.S., Japan, China, and Korea, along with a world-class biologics production facility in Taichung, Taiwan.

For more information about PharmaEssentia USA, visit the website, LinkedIn or Twitter.

About MPN Advocacy & Education International

MPN Advocacy and Education International provides educational programs, materials, and resources for patients, caregivers, physicians, and entire healthcare teams to improve their understanding of myelofibrosis, polycythemia vera, and essential thrombocythemia. They are dedicated to making a difference in the lives of those affected by MPNs and strive to grow awareness and advocate on behalf of the MPN community.

For more information about MPN Advocacy and Education International, visit the website, Facebook or Twitter.

© 2023 PharmaEssentia Corporation. All rights reserved.

PharmaEssentia, the PharmaEssentia logo, and PV&ME are trademarks or registered trademarks of PharmaEssentia Corporation.

1 Griesshammer M, Kiladjian J-J, Besses C. Thromboembolic events in polycythemia vera. Ann Hematol. 2019;98:1071–82. DOI: 10.1007/s00277-019-03625-x
2 Antithrombotic Trialists (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849-1860. https://doi.org/10.1016/S0140-6736(09)60503-1
3 Yusef S, et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. NEJM. 2016;374(21):2021-2031. DOI: 10.1056/NEJMoa1600176
4 Risk and Prevention Study Collaborative Group;​ Roncaglioni M, et al. N-3 fatty acids in patients with multiple cardiovascular risk factors. NEJM. 2013;368:1800-1808. DOI: 10.1056/NEJMoa1205409
5 Barbui T, et al. In contemporary patients with polycythemia vera, rates of thrombosis and risk factors delineate a new clinical epidemiology. Blood. 2014;124:3021-3023. https://doi.org/10.1182/blood-2014-07-591610
6 Cerquozzi S, Tefferi A. Blast transformation and fibrotic progression in polycythemia vera and essential thrombocythemia: a literature review of incidence and risk factors. Blood Cancer J. 2015;5, e366; DOI:10.1038/bcj.2015.95

Read more

Improved Molecular Understanding of AP/BP MPN Better Informs Management Approaches

Posted on by

Tony Berberabe, MPH

Developing an optimal treatment strategy for patients with accelerated- or blast-phase myeloproliferative neoplasms (MPN AP or MPN BP) requires consideration of a patient’s ability to tolerate intensive induction as initial therapy, their eligibility for allogeneic stem cell transplant (ASCT), and whether prior cytoreduction is necessary, according to a presentation by Olatoyosi Odenike, MD, at the 2023 SOHO Annual Meeting.

Few treatment options are available for patients with MPN that is in AP (10% or more blasts) or BP (20% or more blasts), with only ASCT offering the potential for cure, although only a minority of patients are eligible for this intervention. From a targeted therapy perspective, single agent hypomethylating agents (HMAs) or HMAs in combination with ruxolitinib (Jakafi®; Incyte) or venetoclax (Venclexta®; Genentech and AbbVie)can also be considered.

The paucity of approaches coupled with a median overall survival of 3 months for patients who present with BP and 12 to 18 months for patients in the AP adds “urgency to determine who is at highest risk for transformation because that is when intervention can have the most impact,” said Odenike, a professor of medicine and director, Leukemia Program at the University of Chicago Medicine in Illinois.

The treatment choices for initial therapy are affected by the patient’s fitness and ability to undergo intensive induction. However, the choice for pursuing intensive or less intensive induction is somewhat unclear, as prospective randomized trials are lacking. “But retrospective trials that evaluate intense vs less intense approaches portray outcomes evenly, with no clear survival advantage of 1 approach over the other,” Odenike said, bringing up a study by McNamara, et al.2

For this analysis, intensive therapy was defined as chemotherapy; less intensive therapy could include low dose cytarabine, HMAs, or a clinical trial intervention. In the analysis, when intensive therapy was stratified by receipt of ASCT, many of the supposed benefits were found more closely tied to the transplant itself.2 The investigators also noted that patients who underwent intensive therapy but didn’t proceed to transplant had worse outcomes than those who received less intensive therapy.2

“Retrospective studies are subject to all kinds of bias,” Odenike said. “But this study is suggestive that we should have a path forward to transplant if we decide to go the intensive route.”

Molecularly Complex

The high mutational burden and molecular complexity of AP and BP MPN contributes to its poor outcomes, with almost half of patients exhibiting mutations in 4 or more genes. As more is learned about the genes implicated in the disease, the role of targeted therapies becomes more important.

“It’s interesting to think about targeted therapies, since we are starting to better understand the molecular underpinnings of MPNs in general, including when they progress to the accelerated or blast phase,” Odenike said.

Distinct molecular differences exist between AP and BP MPN, which has been referred to as secondary acute myeloid leukemia (AML), and de novo AML, Odenike said. In many cases, AP/BP MPN appears to be enriched for IDH1 and IDH2, making it a potential path for targeted therapies. In particular, IDH1/2 mutations occur in about 25% of patients with BP and leads to epigenetic dysregulation.

IDH1/2 inhibitors have been shown to be active in IDH mutant AML, making these an established treatment for this disease.3,4 For patients with AP/BP MPN, clinical responses to IDH1/2 inhibitors have been positive, with 1 trial reporting a median duration of treatment of 258 days5 and others reporting significant clinical responses to IDH1/2 inhibition.6

As one of the only curative interventions, the focus on getting patients to ASCT and achieving the best responses is paramount. Better responses are seen with ASCT when patients are first cytoreduced and in remission, but outcomes are overall inferior compared with AML that arises de novo, according to Odenike. The same chemotherapy regimens to treat AML are available, but outcomes are not optimal. “Even when the patient is able to have an ASCT, the outcomes are only modestly improved. So, to me, this is a call to action,” Odenike said.

Investigational efforts to explore approaches in the myeloid space are currently focused on epigenomic modulators, novel posttranslational modulators, immune checkpoint inhibitors, and novel targeted agents, including BCL2/BCLXL, IDH1/2, kinase, and MDM2 inhibitors.

Odenike closed with a schema detailing how she treats patients with Philadelphia-negative MPN. In the accelerated and blast phase, she advocates for next-generation sequencing, to identify the molecular profile. “I recommend clinical trial enrollment if available,” she said. “If the patient has a TP53 mutation, those patients generally don’t do well with intensive therapy. With other mutations, I have relative equipoise between intensive and a less intensive approach. But I would only treat using an intensive approach if I had a plan to quickly move the patient to transplant and if the patient is fit.”

References

  1. Odenike O. Managing accelerated- and blast-phase MPN. Presented at: 11th Annual Meeting of the Society of Hematologic Oncology (SOHO 2023). September 7, 2023. Houston, Texas.
  2. McNamara CJ, Panzarella T, Kennedy JA, et al. The mutational landscape of accelerated- and blast-phase myeloproliferative neoplasms impacts patient outcomes. Blood Adv. 2018;2(20):2658–2671. doi:10.1182/bloodadvances.2018021469
  3. Green A, Beer P. Somatic Mutations of IDH1 and IDH2 in the Leukemic Transformation of Myeloproliferative Neoplasms. N Engl J Med. 2010;362(4):369-370. doi: 10.1056/NEJMc0910063
  4. Stein EM, DiNardo CD, Pollyea DA, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017;130(6):722-731. doi:10.1182/blood-2017-04-779405
  5. Patel AA, Cahill K, Charnot-Katsikas A, et al. Clinical outcomes of IDH2-mutated advanced-phase Ph-negative myeloproliferative neoplasms treated with enasidenib. Br J Haematol. 2020;190(1):e48-e51. doi:10.1111/bjh.16709
  6. Chifotides HT, Masarova L, Alfayez M, et al. Outcome of patients with IDH1/2-mutated post–myeloproliferative neoplasm AML in the era of IDH inhibitors. Blood Adv. 2020;4(21):5336–5342. doi:10.1182/bloodadvances.2020001528

Read more

Research Developments Advancing Involving CALR-Mutated MPNs

Posted on by

September 6, 2023

Vicki Moore, PhD

A review article published in the Journal of Cellular and Molecular Medicine details recent progress in the development of antibodies targeting mutated calreticulin, aimed at providing a novel therapy option for myeloproliferative neoplasms (MPN). The review was authored by Frederike Kramer, PhD, and Ann Mullally, MD, of Harvard Medical School in Boston, Massachusetts.

Calreticulin is encoded by the CALR gene and alterations in this gene are common drivers of the development of MPN. In most cases, these occur as 1 of 2 mutations in exon 9 of this gene, as Kramer and Mullally explained in their review. Approximately half of the patients with a CALR mutation have a 52-bp deletion, whereas approximately 30% of patients with a CALR mutation have an insertion of 5 bp in the sequence of this gene.

These types of mutations in CALR lead to a frameshift that causes formation of an altered C-terminus in calreticulin, resulting in the absence of an endoplasmic reticulum retention signal. The altered calreticulin is thus directed toward the cell’s surface, where it shows aberrant binding to the thrombopoietin receptor protein (MPL), with the interaction ultimately contributing to activation of the JAK-STAT signaling pathway and cell transformation.

Currently, patients with MPN are often treated with cytoreductive therapies. Allogeneic stem cell transplantation can be curative for patients with CALR-mutated MPN, but this approach carries risks of morbidity and mortality.

However, the interaction of altered calreticulin and MPL provides a possible substrate for a potential targeted treatment approach. Monoclonal antibodies (mAbs) directed at altered calreticulin have been the subject of research, and a range of studies have generated results indicating this may be a possible approach to treatment of CALR-mutated MPN.

Additional immunological approaches to treating MPN that have been under investigation involve peptide vaccination directed at altered calreticulin and T cell-directed targeting agents. Antibody-drug conjugates could also present a possible avenue of treatment, with these agents potentially binding to both mutated calreticulin and MPL within a complex, rather than binding to mutated calreticulin that has simply been secreted.

“Recent advances in identifying the mechanisms by which mutant calreticulin causes MPN paved the path for immunological targeting of CALR-mutant MPN cells, and specific mutant calreticulin targeting mAbs have been developed and found to be efficacious in preclinical mouse models,” the authors wrote in their report, also noting safety and efficacy with these agents have not yet been evaluated in this patient population.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.

Reference

Kramer F, Mullally A. Antibody targeting of mutant calreticulin in myeloproliferative neoplasms. J Cell Mol Med. Published online August 7, 2023. doi:10.1111/jcmm.17896

Read more

Health Outcomes in Hematologic Malignancies Impacted By Insurance, Marital, and Economic Status

Posted on by

Hayley Virgil

Findings from a systematic review of several observational studies reveal that increasing disparities in survival outcomes within hematologic malignancies can be primarily attributed to 5 social determinants of health: lack of access to health insurance, treatment at a non-academic facility, low income or education level, and unmarried status.

Key takeaways from the review were presented at the 2023 Society of Hematologic Oncology (SOHO) Annual Meeting. The analysis examined survival outcomes in several subgroups of patients with hematologic cancers and compared them with the overall population. Investigators were able to conclude that although survival was improving overall, disparities were only growing.

Results showed that insurance status was significantly associated with survival in the multivariate analysis (76%), subgroup analysis (12%), and unadjusted analysis (3%), and not significant in a small portion (9%). Findings were similar regarding facility type (56%, 17%, 6%, and 22%, respectively). Distance traveled did show some significant association in multivariate (18%) and subgroup analyses (27%), but was primarily found to not be significant (55%). The association of both provider expertise and marital status proved significant in the multivariate analysis (100% each).

When assessing the impact of economic stability and education on outcomes, income had a significant association in the multivariate analysis (63%), as well as in a subgroup (4%) and unadjusted analyses (8%). Similar findings were reported with regard to high school education (44%; 6%; 17%; and 33%, respectively). Employment and nineth grade education were not significantly associated with survival (100%). Poverty was insignificant in the multivariate analysis (26%), and a subgroup (26%), vs not significant in 50% of patients.

“When we compare those [survival] curves with the overall population of the United States, we can see that those improvements have not reached everybody,” Marisol Miranda-Galvis, DDS, MS, PhD, research project manager at Georgia Cancer Center, said during a presentation on the analysis. “There are obvious reasons that could explain those differences, but our interest is to identify what those actions are that clinicians could implement in clinical practice, regardless of limitations, that could help to close that gap.”

Investigators defined social determinants of health (SDH) as a “set of non-biologic factors that shape the environment of daily life that influence health outcomes.” Such factors include education access and quality, health care access and quality, social and community context, economic stability, and neighborhood/built environment. The goal of the analysis was two-fold: identify the SDH that have been assessed with regard to their impact on outcomes and determine which SDH were linked with worse treatment-related outcomes.

To be included in the systematic review, several criteria were required during the literature search:

  • Patients must have had a hematologic cancer,
  • Any SDH,
  • No comparisons,
  • Any treatment survival measures,
  • Observational studies held in the United States.

The review included a total of 24,353 patients (range, 95-132,402). The most common study setting was national (63.4%), and the most common data source was the National Cancer Database (41.5%). Several types of hematologic malignancies were included in the review, including Hodgkin lymphoma, non-Hodgkin lymphoma, and Burkitt lymphoma (34.1%); multiple myeloma and polymyositis (31.7%); acute myeloid leukemia, acute lymphocytic leukemia, and myelodysplastic syndrome (29.3%); and chronic myeloid leukemia and chronic lymphocytic leukemia (4.9%).

In a population of 57 patients, the outcomes evaluated in the included studies were overall survival (73.2%), early mortality (10.7%), cancer-specific survival (8.9%), progression-free survival (3.6%), and disease-free survival and treatment-related mortality (1.8% each).

SDH that were evaluated were health care access (53.0%), including insurance status (47.1%) and facility type (28.5%); economic stability (25.0%), including income (81.8%) and poverty (12.1%); education access (14.4%), including high school education (94.7%); and social context (7%), including marital status (100%).

When looking specifically at health care access (n = 70) and social context (n = 10), Miranda-Galvis shared several key takeaways.

“In terms of health care access, this domain was evaluating insurance status; those with Medicaid, Medicare, and who were uninsured had lower survival rates compared with those with private or military health coverage,” she said. “In terms of facility type where the patients were treated, those who didn’t receive treatment at an academic institution or research institution presented with a [worse] mortality compared with those who received treatment at community, comprehensive, or integrated cancer centers.”

Several economic stability (n = 33) and education (n = 19) factors were also associated with a survival disadvantage, including having a lower income and education level. The impact of poverty rate appeared inconclusive, while no significant correlations were observed from unemployment rate, and ninth grade education level.

Reference

Miranda-Galvis M, Tjioe K, Balas A, Cortes J. Cancer disparities in survival of patients with hematologic malignancies in the context of social determinants of health: a systematic review. Presented at: 2023 Society of Hematologic Oncology (SOHO) Annual Meeting; September 6-9, 2023; Houston, TX. Abstract MDS-044.

Read more

Understanding Different Types of Blood Cancers and Diagnostic Procedures

Posted on by

September 3, 2023

Jaishankar Chigurula

Blood cancers encompass a diverse range of types, each with its own set of symptoms and characteristics. Early detection and appropriate diagnostic procedures are crucial for effective treatment and management of these conditions. By recognizing the common symptoms and undergoing comprehensive testing, individuals can increase their chances of early intervention and improved outcomes.

Leukaemia

Leukaemia is a blood cancer that originates in the bone marrow and affects white blood cells, compromising the body’s immune response. Common subtypes include Acute Myeloid Leukaemia (AML) and Acute Lymphoblastic Leukaemia (ALL).

Lymphoma

Lymphomas are blood cancers that target the lymphatic system and involve abnormal lymphocyte growth. Examples of lymphomas include Hodgkin lymphoma and non-Hodgkin lymphoma. These cancers can lead to the enlargement of lymph nodes and other organs.

Multiple Myeloma

Multiple Myeloma is a blood cancer that affects plasma cells, which are crucial for immune function. The overproduction of abnormal plasma cells can damage bones and other organs.

There are also related blood diseases that can progress to Acute Leukaemia:

Myelodysplastic Syndromes (MDS)

MDS is characterized by faulty bone marrow function, resulting in insufficient production of healthy blood cells. In some cases, MDS can progress to acute leukaemia.

Myeloproliferative Neoplasms (MPN)

MPNs are a group of diseases where the bone marrow produces too many specific blood cells. Examples include polycythemia vera, essential thrombocythemia, and myelofibrosis.

Recognizing the symptoms of blood cancers is essential for early detection. While the symptoms can vary depending on the specific type and stage of the cancer, there are common indicators to be aware of. Comprehensive blood tests can reveal abnormal cell counts, types, and characteristics, providing crucial insights into potential blood cancer presence. Bone marrow tests involve the extraction of samples for analysis, aiding in identifying specific cancer types and assessing disease progression.

Specialized testing techniques, such as Flowcytometry immunophenotyping, Cytogenetics, Immunohistochemistry, and Molecular techniques like PCR, Sequencing, and NGS, are used to aid in diagnosis, lineage determination, prognosis, and monitoring of blood cancers. Imaging tests such as CT scans, PET scans, and X-rays help visualize the extent of cancer spread and the involvement of lymph nodes and other organs.

A thorough physical examination can also help identify visible symptoms, such as enlarged lymph nodes, that might indicate blood cancer. In some cases, surgical removal of lymph nodes may be necessary for accurate staging and prognosis determination.

Early detection and prompt diagnosis of blood cancers can significantly improve treatment outcomes. If you experience any concerning symptoms or have a family history of blood cancers, it is important to consult with a healthcare professional for appropriate testing and evaluation.

 

Renin Angiotensin Inhibitors Reduce Thrombotic Adverse Effects in Chronic Myeloproliferative Neoplasms

Posted on by

Kyle Doherty

Patients with essential thrombocythemia and polycythemia vera who also had arterial hypertension experienced a higher cumulative incidence of thrombotic adverse effects compared with those without hypertension and fewer thrombotic complications following treatment with renin angiotensin system inhibitors.

Patients with essential thrombocythemia and polycythemia vera (PV) who also had arterial hypertension experienced a higher cumulative incidence of thrombotic adverse effects (AEs) compared with those without hypertension and fewer thrombotic complications following treatment with renin‑angiotensin system (RAS) inhibitors, according to findings from a retrospective study published in Annals of Hematology.

In the overall cohort of patients with myeloproliferative neoplasms (MPNs; n = 404), treatment with RAS inhibitors conferred a protective effect from thrombotic AEs (HR, 0.46; 95% CI, 0.21-0.98; P = .04), including those with a thrombotic high-risk score (n = 272; HR, 0.49; 95% CI, 0.24-1.01; P = .04). Moreover, patients with essential thrombocythemia and a thrombotic high-risk score experienced an especially defined benefit following treatment with RAS inhibitors (HR, 0.27; 95% CI, 0.07-1.01; P = .03).

“The main goal of managing MPNs is to prevent thrombotic incidents,” study authors wrote. “The results indicated that patients [with MPNs] had a significantly higher risk [4.9-fold] of arterial thrombosis than the healthy controls. We found a protective association between the use of RAS inhibitors and the reduction in thrombotic AEs in our cohort of patients [with MPNs].”

To conduct their study, investigators collected data from patients diagnosed with PV or essential thrombocythemia by WHO 2016 classification who were treated at the Hematology Unit of the Businco Hospital in Cagliari, Italy, from November 2000 through August 2021. Patients with PV were stratified by low risk of developing thrombosis (age < 60 years and no history of thrombosis) and high risk of developing thrombosis (age ≥ 60 years or a history of thrombosis). Patients with essential thrombocythemia were stratified by International Prognostic Score for Essential Thrombocythemia score, cardiovascular risk factors, age over 60 years, thrombosis history, and the presence of a JAK2 V617F mutation. Study authors also collected clinical data at the time of diagnosis, including constitutional symptom, performance status, hemoglobin, white blood cell counts, and the presence of somatic driver gene mutations among other data.

Patients had PV (n = 133) or essential thrombocythemia (n = 271). The median age at diagnosis was 63 years (range, 17-98) and the median follow-up was 5.5 years (range, 0-24) in the overall population. Most patients had comorbidities at diagnosis (70%) and a high thrombotic risk score (67.3%). Cardiovascular AEs experienced before (66.3%) MPN diagnosis included ischemic heart disease (7.7%), peripheral arterial disease (3.5%), cerebrovascular event (6.9%), atrial fibrillation (6.2%), deep vein thrombosis (4.7%), and other (4.2%); after diagnosis, thrombotic AEs (15.0%) that occurred were ischemic heart disease (3.5%), peripheral arterial disease (2.9%), cerebrovascular event (3.7%), and deep vein thrombosis (4.4%).

Most patients also had a positive mutational status (89.3%), including mutations in JAK2 V617F (78.5%), calreticulin (8.9%), and MPL (1.5%); 48.2% of patients also had essential thrombocythemia JAK2 V617F positivity. The therapies received for MPNs were low-dose aspirin (72.3%), phlebotomy (30.0%), cytoreduction therapy (62.9%), and IFN-2a (0.2%).

Median values were 10.5 × 103 /μL (range, 1.0-96.1) for leukocytes, 15.0 g/dL (range, 7.0–15.0) for hemoglobin, and 696 × 103/μL (range, 87–2320) for platelets. Median hematocrit was 48% (range, 29.0%-77.0%).

Investigators noted that “there was a significant difference in the JAK2 V617F mutation status within the group of patients [with essential thrombocythemia] with hypertension (27% vs 21.2%, P = .01).”

Most patients in the study had hypertension (53.7%) and in this subgroup, patients had PV (n = 78/217) and essential thrombocythemia (n = 139/217). Those with positive mutational status (n = 197/217) had JAK2 V617F (n = 182/217), calreticulin (n = 12/217), MPL (n = 3/217), and essential thrombocythemia– positive JAK2 V617F (n = 109/217) mutations. Median values were 10.9 × 103/μL (range, 1.09-19.2) for leukocytes, 15.2 g/dL (range, 10.4-21.0) for hemoglobin, and 720 × 103/μL (139–1170) for platelets. Median hematocrit was 47.6% (range, 33.1%-69.0%).

The majority of patients with hypertension had cardiovascular AEs before being diagnosed with an MPN (n = 216/217) including ischemic heart disease (n = 20/217), peripheral arterial disease (n = 7/217), cerebrovascular event (n = 19/217), atrial fibrillation (n = 15/217), deep vein thrombosis (n = 11/217), and other (n = 9/217); after diagnosis, 39 patients experienced thrombotic AEs; these included ischemic heart disease (n = 10/217), peripheral arterial disease (n = 6/217), cerebrovascular event (n = 12/217), and deep vein thrombosis (n = 11/217).

Additionally, patients with hypertension underwent prior hypertension therapy with a RAS inhibitor (n = 147/217) including angiotensin receptors blockers (n = 87/217), angiotensin-converting enzyme inhibitors (n = 59/217), and inhibitors without association (n = 116/217). Calcium antagonists were given to 52 patients and other agents including thiazide diuretics, beta-blockers, and doxazosin were given to 101 patients. Patients with hypertension also received treatment with low-dose aspirin (148/217), phlebotomy (70/217), cytoreduction therapy (159/217) and IFN-2a (1/217) as therapy for their MPN.

Additional findings showed that the cumulative incidence of thrombotic AEs over 15 years was significantly higher among patients with hypertension (66.8% ± 10.3%) compared with those without (38.5% ± 8.4%; HR, 1.83; 95% CI, 1.08-3.1). Findings from a multivariate analysis also revealed that hypertension (HR, 1.8; 95% CI, 0.983-3.550; P = .05) and PV diagnosis (HR, 3.5; 95% CI, 1.928-6.451; P < .001) were both associated with an increased risk of developing thrombotic AEs. Considering only patients with MPNs and hypertension, diagnosis of PV displayed a predictive role in developing thrombotic AEs (HR, 4.4; 95% CI, 1.92-10.09; P < .01).

“In conclusion, to improve the treatment of patients with MPNs, it is crucial to pay close attention to their cardiovascular risk factors, as these factors play a significant role in the complications of the disease. A more targeted approach could provide more effective and personalized care for patients with MPNs. Although the study’s retrospective nature poses limitations, the robust connections between the RAS system and hematological disorders make it crucial to conduct a more comprehensive analysis of the effects of RAS inhibitors on MPNs,” investigators wrote in summary.

Reference

Mulas O, Mola B, Costa A, et al. Renin-angiotensin inhibitors reduce thrombotic complications in essential thrombocythemia and polycythemia vera patients with arterial hypertension. Ann Hematol. Published online August 21, 2023. doi:10.1007/s00277-023-05417-w

Read more