Tag Archives: treatment

Treatment Differences for Younger vs Older Patients With MPNs

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October 30, 2024

Author(s): Laura Joszt, MA, Mary Caffrey

The age distribution of people affected by myeloproliferative neoplasms (MPNs) is broad, explained Ruben Mesa, MD, FACP, executive director of Atrium Health Wake Forest Baptist Comprehensive Cancer Center, president of Atrium Health Levine Cancer.

With younger patients, it’s important to understand the increased risk of their disease progressing given how long they’ll live with their illness, and the impact therapies may have on fertility.

This transcript was lightly edited for clarity.

Transcript

About 20% of patients with myeloproliferative neoplasms are in the adolescent to young adult population. Are there characteristics that differentiate this younger population from older ones or treatment considerations that differ among the age groups?

I would say that the median age is in the 60s. However, I would say that the distribution is broad. As opposed to it being a median in the 60s and there being a high concentration only in individuals that are older, it is a broader distribution. In particular the earlier phases of MPN, ET [essential thrombocythemia], and PV [polycythemia vera}, are not uncommon in those that are 30s, 40s and 50s years old. Teenagers and those in their 20s—that AYA [adolescent and young adult] population—certainly is less common, but it is more common than, I think, had been appreciated, that there’s a broader distribution affecting these individuals.

Clearly, with younger individuals, we’re mindful of several things. One, the length of time that they have the illness does increase our concern that they have a higher risk of the disease progressing to a more advanced myeloid neoplasm the longer they have the disease. Particularly individuals with 10 years or more of the disease have increasing risk from ET and PV progressing to myelofibrosis. Overall, we think myelofibrosis can be a life-threatening disease, where ET and PV usually can be managed without a decrease in survival. So, that progression is really a negative, and the younger you are, the more exposure you really have to that. Additionally, they have a higher risk of progressing to acute leukemia because of this increased length of time.

Additionally, there are issues as it relates to both the preservation of fertility and the selection of medical therapy. Historically, in ET and PV, there had been a lot of use of the medication hydroxyurea, that is counter indicated in pregnancy, and that has implications in terms of therapy selected, so that medications like interferons or long-acting interferons tend to be preferred in this group of patients, both for that reason, as well as there is the data suggesting that interferons may help to slow the progression of the disease. And again, in younger individuals, that makes it a more relevant therapy for these individuals.

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Researchers Identify INCA033989 as a Potential Treatment for Myeloproliferative Neoplasms

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By Alexandra Gerlach, Associate Editor

Data from a study published in Blood demonstrates the therapeutic potential of INCA033989 as the first targeted therapy for myeloproliferative neoplasms (MPNs) that does not interfere with normal blood cell production. Existing therapeutic options for MPNs are effective at symptom management but have high discontinuation rates due to resistance and inadequate drug tolerability. The development of INCA033989 opens pathways to more effective, targeted options with disease-modifying potential without any negative impact on surrounding blood cells.1

The development of INCA033989 has positive implications for the evolving treatment landscape of patients with MPNs. Image Credit: © Anna – stock.adobe.com

MPNs are a group of malignancies characterized by the overproduction of red and white blood cells and is an umbrella for 6 different disease types: myelofibrosis (MF), essential thrombocythemia, chronic myelogenous leukemia, polycythemia vera, chronic neutrophilic leukemia, and chronic eosinophilic leukemia. Calreticulin (CALR) mutations are responsible for disease development in 20% to 30% of patients with MPNs, which can be either insertions or deletions in exon 9 of CALR. The mutated CALRprotein (mutCALR) is responsible for the stable interaction with thrombopoietin receptors (TPO-R), which are crucial for controlling blood cell production.2,3

Janus kinase (JAK) inhibitors, such as ruxolitinib (Jakafi; Incyte Corp), are the recommended treatment options for patients with MF or other MPNs; however, they are associated with adverse effects (AEs), namely grade 3 or 4 anemia. INCA033989 is a high affinity, fully human immunoglobulin G1 selective monoclonal antibody targeting mutCALR-driven oncogenesis to suppress TPO-R signaling, thereby preventing the proliferation and progression of disease. According to data from the original study announcing the development of this agent, there was an observed synergism between INCA033989 and ruxolitinib which resulted in the inhibition of cell proliferation and indicated the ability of INCA033989 to enhance the efficacy of ruxolitinib.3,4

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New Data Challenge Traditional Treatment Paradigm in MPNs, Says Dr Raajit Rampal

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Laura Joszt, MA

New data challenge the traditional thinking that low-risk patients with myeloproliferative neoplasms are largely just treated with phlebotomy and aspirin and have shown the benefits of medication, such as ropeginterferon, said Raajit Rampal, MD, PhD, hematologic oncologist, associate attending physician, Memorial Sloan Kettering Cancer Center.

Transcript

Interferons have been around for decades, but what unanswered questions remain about their use?

I think it really is about: when to start, who starts, and for how long should they be treated? Those, to me, are kind of key questions. There’s relatively recent data that looked at treating patients with polycythemia vera, who are low risk with ropeginterferon vs what we traditionally do, which is to use things like phlebotomy and aspirin. There at least seems to be some signal to suggest that those patients may derive a benefit. Our traditional thinking is we leave the patients alone except for phlebotomy and aspirin, and if they have a blood clot or symptoms or something, maybe we put them on medication. If not, we only treat them if they’re high risk. But this data was actually provocative in the sense that it said, “Well, if you take these low-risk patients, there may be some clinical benefits to them by starting early.”

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New study paves the way for precision drugs to treat blood cancers

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by Tampere University

April 4, 2024

The Janus kinase 2 (JAK2) protein mediates signaling from several cytokine receptors in the regulation of hematopoiesis and immune responses. Somatic mutations in human JAK2 lead to constitutive activation and cytokine-independent signaling and underlie several hematological malignancies from myeloproliferative neoplasms (MPN) to acute leukemia and lymphomas. JAK2 contains an active kinase domain and an inactive pseudokinase domain. Interestingly, pathogenic mutations mainly occur in the regulatory pseudokinase domain.

Due to its critical pathogenic role, JAK2 has become an important therapeutic target. The four currently approved JAK2 inhibitors relieve symptoms but do not heal the patient or affect survival. These drugs target the highly conserved kinase domain and affect both normal and mutated JAK2 and, due to side effects, carry a black box warning that limits their use in elderly, cardiac and cancer patients. The selective inhibition of pathogenic JAK2 is a key pending goal in drug discovery that requires a precise mechanistic understanding of the regulation of JAK2 activation.

“To understand the molecular and structural basis of the physiological and pathogenic activation of JAK2, we used single-molecule microscopy and erythropoietin receptor (EpoR) as a model system.

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Younger Patients With PV May Benefit From Earlier Treatment With Cytoreductive Therapies

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Laura Joszt, MA

Although patients younger than age 60 with polycythemia vera (PV) are typically not treated with cytoreductive therapy due to treatment toxicity concerns, this may result in an undertreatment of patients as there is no clear evidence that the risk of toxicity exceeds the potential benefit of treatment, according to a study published in Blood Advances.1

PV causes an overproduction of blood cells in the bone marrow, which leads to high numbers of circulating red blood cells.2 This thickens the blood, which may not flow through smaller blood vessels properly. Although PV can be diagnosed at any age, it most often occurs in people over the age of 60 years.2

For most patients, phlebotomy is the standard treatment, and it may be the only treatment needed for years. However, additional treatment to suppress the formation of blood cells in the bone marrow may be needed. Cytoreductive therapies, such as interferons, hydroxyurea, ruxolitinib, and anagrelide, may be needed, particularly for high-risk patients.3

Currently, cytoreductive therapies are not routinely recommended by the European LeukemiaNet or National Comprehensive Cancer Network for patients with PV younger than 60 years who don’t have a history of thrombosis, a high symptom burden, or an intolerance to phlebotomy.

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