Category Archives: Treatment

Pelabresib Plus Ruxolitinib Significantly Reduces Splenomegaly in Myelofibrosis

Posted on by

Kristi Rosa

Pelabresib (CPI-0610) plus ruxolitinib (Jakafi) significantly reduced splenomegaly, showed a trend toward a reduction in tumor symptom score (TSS) from baseline, and improved bone marrow fibrosis and anemia at week 24 compared with ruxolitinib alone in JAK inhibitor–naive patients with myelofibrosis, according to updated data from the phase 3 MANIFEST-2 study (NCT04603495) presented at the 2024 ASCO Annual Meeting.1

As previously presented at the 2023 ASH Annual Meeting, the trial met its primary end point when a higher percentage of those who received the doublet (n = 214) experienced a 35% or greater reduction in spleen volume (SVR35) at week 24 vs those given ruxolitinib alone (n = 216), at 65.9% and 35.2%, respectively (difference, 30.4; 95% CI, 21.6-39.3; P < .001).2 The mean percentage change in spleen volume at week 24 in the pelabresib/ruxolitinib arm was -50.6% (95% CI, -53.2% to -48.0%) vs -30.6% (95% CI, -33.7% to -27.5%) in the ruxolitinib-alone arm.

When looking at all responders who achieved SVR35 response, the proportion who lost response at any point in the pelabresib/ruxolitinib arm was 13.4% and more than double in the ruxolitinib-alone arm, at 27.8%. When examining the criteria of loss of SVR35 response plus a spleen volume increase greater than 25% from nadir, this occurred in 9.3% and 14.8% of patients, respectively. Notably, SVR35 response was consistently higher with the doublet vs the monotherapy across all predefined subgroups and across hematologic subgroups.

Read more

Advances in Interferon Therapy for Myeloproliferative Neoplasms

Posted on by

Kumar Das, Dibash PhD

Oncology Times 46(6):p 1,14, June 2024. | DOI: 10.1097/01.COT.0001024068.38723.15

In the ever-evolving landscape of myeloproliferative neoplasms (MPNs), clinicians continue to explore and refine treatment strategies to improve patient outcomes. A recent review published in Therapeutic Advances in Hematology sheds light on the pivotal role of interferons, particularly pegylated formulations, in managing MPNs effectively (2024; doi: 10.1177/20406207241229588).

The advent of pegylated interferons, including peginterferon alfa-2a and ropeginterferon alfa-2b-njft, marks a significant turning point in MPN therapeutics. These agents, renowned for their potent immunomodulatory capabilities and profound impact on disease progression, have reshaped treatment paradigms outlined in the National Comprehensive Cancer Network (NCCN) Guidelines for polycythemia vera (PV), essential thrombocythemia, and primary myelofibrosis. This article delves deep into the multifaceted influence of pegylated interferons, shedding light on their efficacy, safety profiles, and future implications in MPN management.

Clinical trials, including landmark Phase II and III studies such as MPD-RC 111 and MPD-RC 112, have provided crucial insights into the efficacy of pegylated interferons. These trials meticulously assessed response rates, molecular remissions, and hematological improvements in MPN patients resistant to or intolerant of hydroxyurea. Noteworthy reductions in JAK2 V617F variant allele frequency (VAF) have underscored the molecular response achievements of pegylated interferons, highlighting their disease-modifying potential.

Read more

Pooled Analysis Shows Cytoreduction to Be Safe, Tolerable in Younger Patients With PV

Posted on by

Ashling Wahner

Cytoreductive therapy with interferon alfa (rIFNα) or hydroxyurea is safe and well tolerated in patients with polycythemia vera (PV) under the age of 60 years and induces annualized discontinuation rates comparable to those reported with these agents in older patients with PV, for whom cytoreductive therapy is routinely used, according to findings from a meta-analysis that were published in Blood Advances.1

Across the 14 studies included in this analysis, rIFNα discontinuation rates ranged from 4.6% to 37% over median durations of 0.4 to 6.3 years. Hydroxyurea discontinuation rates ranged from 2.6% to 17% over median durations of 0.5 to 14 years.

Although the use of cytoreductive agents, such as rIFNα and hydroxyurea, is associated with reduced thrombosis risk in PV, these agents are not routinely recommended by the European LeukemiaNet (ELN) or the National Comprehensive Cancer Network (NCCN) for patients with PV under the age of 60 years. The ELN recommends cytoreductive therapy for patients with PV who are younger than 60 years of age and have not had prior thrombotic events provided that they have strictly defined phlebotomy intolerance, symptomatic progressive splenomegaly, persistent or progressive leukocytosis, extreme thrombocytosis, persistently high cardiovascular risk, inadequate hematocrit control requiring phlebotomies, and/or persistently high symptom burden.2 The NCCN does not recommend cytoreductive therapy as initial treatment for patients with low-risk disease.3

“Unfortunately, effective and potentially life-prolonging cytoreductive therapy is often deferred in younger patients who are considered ‘low-risk’ because of their age and lack of thrombosis history,” senior study author Ghaith Abu-Zeinah, MD, an instructor in medicine at Weill Cornell Medical College and an assistant attending physician at the NewYork Presbyterian Hospital in New York, New York, and coauthors, wrote in the paper.1 “The rationale for withholding cytoreductive therapy is data-sparse and driven by theoretical concerns for toxicity and unknown benefits from early treatment. Yet, there is some evidence that early treatment is both well tolerated and potentially useful.”

Read more

Direct and indirect costs for patients with myeloproliferative neoplasms

Posted on by
Jingbo Yu, James Nelson, Taylor Marlin, Evan Braunstein, & Michelle Jerry

Abstract

Myeloproliferative neoplasms (MPNs) are associated with substantial healthcare resource use and productivity loss. This retrospective cohort analysis used disability leave and medical claims data to measure direct and indirect healthcare costs associated with MPNs. The analysis included 173 patients with myelofibrosis (MF), 4477 with polycythemia vera (PV), 6061 with essential thrombocythemia (ET), and matched controls (n = 519, n = 13,431, and n = 18,183, respectively). Total healthcare costs were significantly higher for cases versus controls in each cohort (mean cost difference: MF, $67,456; PV, $10,970; ET, $22,279). Cases were more likely than controls to take disability leave and incurred higher disability-related costs. Among subgroups with thrombotic events, direct and indirect costs were higher for cases versus controls. Thrombotic events substantially increased direct costs and disability leave for patients with PV or ET compared with the full PV or ET cohorts. These findings demonstrate increased economic burden for patients with MPNs.

Read more

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

Posted on by

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.”

Read more

Utilization of Momelotinib for Myelofibrosis With Anemia Can Result in Small Savings

Posted on by

Laura Joszt, MA

Although momelotinib to treat myelofibrosis (MF) with anemia has a higher acquisition cost, it is partially offset by savings when transfusion-related costs are reduced, according to a poster being presented at the AMCP Annual Conference, held April 15-18, 2024, in New Orleans, Louisiana.1

MF is a rare cancer in the bone marrow that disrupts the production of blood cells.2 MF causes anemia because of the extensive scarring to bone marrow. This extensive scarring also causes patients to have a low number of platelets, increasing their risk of bleeding. Patients may also have an enlarged spleen.

Momelotinib inhibits Janus kinase (JAK) 1, JAK2, and activin A receptor type 1. In September 2023, the FDA approved momelotinib to treat patients with intermediate- or high-risk MF with anemia.3

The approval of momelotinib was based on data from the phase 3 MOMENTUM trial, which found clinically significant improvements for patients treated with momelotinib vs danazol.4 A quarter of patients treated with momelotinib had a 50% or greater reduction in total symptom score compared with only 16% of patients on danazol.

Since the approval, the National Comprehensive Cancer Network (NCCN) has added momelotinib5 to its Clinical Practice Guidelines in Oncology for Myeloproliferative Neoplasms. Momelotinib was added as a category 2A treatment for patients with high-risk MF. It was also added as a 2B category treatment for patients with lower-risk MF.

Patients with MF who have anemia and are dependent on transfusions have increased medical costs and poor prognosis, the authors of the AMCP poster noted. JAK inhibitors may provide improvements in symptoms and spleen size, but they could worsen or induce anemia. However, momelotinib has been shown to reduce spleen size.4

Read more

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

Posted on by

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.

Read more

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

Posted on by

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.

Read more

Pegylated Interferons Have Promise but Also Unmet Potential in MPNs

Posted on by

Jared Kaltwasser

Pegylated interferons are a meaningful therapeutic option for the treatment of myeloproliferative neoplasms (MPNs), but a new review article says more research is needed to better understand the ideal usage of the therapy.

The report was published in Therapeutic Advances in Hematology.

Study investigators said several interferon products are currently available to treat patients with MPNs, but they said the short half-life of interferons and the risk of (AEs) effects have limited their usage. Pegylation can help overcome those issues, they said.

“Many of these shortcomings were addressed by covalently binding polyethylene glycol to the interferon structure, which increases the stability, prolongs activity, and reduces immunogenicity of the molecule,” the authors wrote.

More research is needed to better understand when and in whom pegylate interferon therapy is most effective | Image Credit: Iamnee – stock.adobe.com

They said current National Comprehensive Cancer Network guidelines call for pegylated interferons to be used for polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Currently, there are 2 pegylated interferons available for patients with MPNs, they said: peginterferon alfa-2a (Pegasys; pharma&) and ropeginterferon alfa-2b-njft (BESREMi; PharmaEssentia). Both medications are recommended as cytoreductive therapies for PV, the investigators said.

Years After Genetic Finding, Drugs Targeting CALR-Mutant Myeloproliferative Neoplasms Enter Trials

Posted on by
Feb 29, 2024 | Catherine Shaffer

NEW YORK – More than a decade after mutations in the CALR gene were first linked to the development of myeloproliferative neoplasms, CALR-targeted drug candidates are advancing to Phase I clinical trials.

If these drugs reach the market, they could provide a treatment option for a group of patients with myelofibrosis and essential thrombocythemia who typically must wait until their condition turns serious to attempt a risky stem cell transplant.

About 300,000 patients in the US have myeloproliferative neoplasms. Kapila Vigas, CEO of the MPN Research Foundation, said patients can have very different presentations of the disease, and it can take “years or decades” to get a diagnosis. Although myeloproliferative neoplasms are classified as chronic cancers that patients can live with for many years with blood count monitoring, Vigas said some patients can abruptly progress, and their condition can become serious.

“That uncertainty is really concerning to patients,” Vigas said. “We think from a psychosocial perspective, it’s worse than an acute cancer because while cancer may be more serious, it’s predictable, and there’s a plan and a protocol, whereas when you’re diagnosed with [a myeloproliferative neoplasm] watch and wait is almost a first-line approach. It just adds to the anxiety.”

Read more