FDA Approval of Momelotinib May Establish New SOC for Myelofibrosis With Anemia

Posted on by

November 2, 2023

Courtney Flaherty

The JAK1/JAK2 and ACVR1 inhibitor momelotinib (Ojjaara) not only provides spleen volume and constitutional symptom benefits in patients with anemic symptomatic myelofibrosis that is noninferior to that achieved with available JAK inhibitors, but may meaningfully reduce disease-related anemia symptoms that standard-of-care agents or danazol do not address, according to Andrew T. Kuykendall, MD. He added that the agent’s recent approval in this population requires re-evaluation of current approaches for managing these aspects of the disease.

On September 15, 2023, the FDA approved momelotinib for the treatment of patients with intermediate- or high-risk myelofibrosis, including primary or secondary myelofibrosis, and disease-related anemia.1,2 Findings from the phase 3 MOMENTUM trial (NCT04173494), as well as data from a subpopulation of adult patients with anemia from the phase 3 SIMPLIFY-1 trial (NCT01969838), supported the regulatory decision.

Twenty-five percent of patients with symptomatic and anemic myelofibrosis who were previously exposed to a JAK inhibitor experienced at least a 50% reduction in tumor symptom score (TSS) with momelotinib vs 9% of patients treated with danazol, which translated to a treatment difference of 16% (95% CI, 6%-26%; P < .01). Additionally, 30% of patients in the momelotinib arm achieved transfusion independence (TI) vs 20% of those in the danazol arm, which translated to a noninferiority treatment difference of 14% (95% CI, 2%-25%; P = .023). Spleen volume reduction and a decrease in anemia-related symptoms were also observed with momelotinib.3

“[With momelotinib], we’re extending the benefits of JAK inhibition to more people and we’re potentially helping [to ameliorate] anemia, which has been an area of unmet need for a long time for patients with myelofibrosis,” said Kuykendall, who is an assistant member of the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, Florida.

In an interview with OncLive®, Kuykendall discussed the importance of this approval for treating patients with anemic symptomatic myelofibrosis in clinical practice, key efficacy and safety data from the MOMENTUM trial that supported the decision, and unanswered questions regarding the agent’s potential role in other subsets within this population.

OncLive: What is the significance of the recent FDA approval of momelotinib for patients with myelofibrosis and anemia?

Kuykendall: This decision represents our further advancement in the perpetual story of [managing patients with] myelofibrosis [over] the past decade. On one hand, [we’re] trying to bring JAK inhibition to as many patients with myelofibrosis as possible. Ruxolitinib [Jakafi] really changed the game in myelofibrosis by allowing patients to [experience] profound improvement of splenomegaly and disease-related symptoms; it is also associated with a modest survival benefit. However, we continue to run into issues with patients who have anemia, which is most patients with myelofibrosis. [These patients, as well as those] who have low platelets, can’t experience the full benefit of JAK inhibition. The accelerated approval of pacritinib [Vonjo] helped with some aspects of that.

Now, momelotinib [provides] a full dose of a potent JAK inhibitor for patients who are anemic and may even be able to help with that anemia, as well. On the flip side, it looks like it can help with patients [who have] low platelets, as well. [The MOMENTUM trial] enrolled [patients] [with a] platelet count [of more than 25 x 109 cells/L].

What is unique about the mechanism of action of momelotinib compared with other JAK inhibitors?

All of the main approved agents in myelofibrosis are JAK2 inhibitors. However, their kinase inhibition profiles serve as differentiating factors. Momelotinib is a bit different in the sense that, like ruxolitinib, it [targets] JAK1 and JAK2. Pacritinib, and to a lesser extent, fedratinib [Inrebic], are more selective for JAK2. [Momelotinib] also inhibits ACVR1, which we believe plays a key role in modulating hepcidin and improving anemia. This potentially distinguishes momelotinib from ruxolitinib.

Now, instead of worsening anemia, which we often see happen with ruxolitinib or fedratinib, we’re able to get those symptom and spleen benefits [that come with] JAK1/JAK2 inhibition, and at the very least, mitigate some of the anemia we saw with ruxolitinib. [Momelotinib could] potentially lead to an overall improvement in anemia and fewer transfusions for patients.

Could you expand on the design of the MOMENTUM trial, and the patient population enrolled?

The MOMENTUM trial was the third phase 3 trial of momelotinib. Ultimately, the trial enrolled patients who had previously been exposed to ruxolitinib, were anemic, had some degree of myelofibrosis-related symptoms, and had splenomegaly. Patients didn’t have to be [treated with] ruxolitinib for a long time. They could have been on it for just about a month, [during which] they had some anemia. Those patients were randomly assigned 2:1 to either momelotinib or danazol, which we know is a control. This means that we use the agent for patients who are anemic.

What key efficacy findings were reported?

The primary end point of the trial was symptom improvement and aimed for a 50% reduction in TSS. Overall, we expected to see improvement with momelotinib over danazol, [However], we know that symptoms can be related not just to inflammatory cytokines or to splenomegaly but can also occur due to anemia. We expected danazol to help with some of those [symptoms]. Some key secondary end points [included] some improvement in splenomegaly reduction compared with danazol. Although the results didn’t meet the criteria for superiority, TI rate [with momelotinib] was nominally better than the rate [observed with danazol]. More patients on the momelotinib arm were TI after 24 weeks vs [those in] the danazol arm with essentially an equal number [transfusion dependent between groups] at baseline.

Spleen response rates [with momelotinib] are similar to what you might expect to see with ruxolitinib or another JAK inhibitor. However, momelotinib has been directly compared with ruxolitinib in the SIMPLIFY-1 trial, where treatment-naive patients were randomly assigned to momelotinib or ruxolitinib. In that trial, momelotinib was noninferior to ruxolitinib in terms of spleen responses. Therefore, we know it is a potent JAK inhibitor in terms of inducing spleen responses. It was exciting to see results play out like that in this pivotal trial.

What should be known about the safety profile of momelotinib?

[The toxicities associated with momelotinib] are relatively benign. When we think about JAK inhibitors, we consider the safety profiles. In general, these are palliative medications that we’re using to make people feel better and improve quality of life and functionality. If our ultimate goal is for people to feel better, we need these agents to be well tolerated. When one of our key findings is symptoms improving, you can see that these are well-tolerated medications. In the short term, patients are reporting that they feel better than they did previously after going on these medications.

In terms of things to watch out for, there’s a mild increase in gastrointestinal [GI] toxicity vs what was seen with danazol. Still, these rates are relatively low for those experiencing nausea, which is also usually low grade. This is probably lower than what we have seen in other trials with pacritinib and fedratinib that inhibit FLT3, as anything that inhibits FLT3 is associated with some degree of GI toxicity.

In previous trials, there was some concern for peripheral neuropathy, which wasn’t really seen in the MOMENTUM study. There were relatively low rates of anemia and thrombocytopenia. In fact, this agent is likely to improve, or at least stabilize, anemia and was leveraged safely in patients with a quite low platelet count. Overall, there’s not too much to be concerned about [regarding] hematologic adverse effects. [Additionally,] momelotinib actually had fewer adverse effects on the kidneys than danazol did.

With this approval, where do you see momelotinib fitting into the treatment paradigm in myelofibrosis?

The clearest answer is [that it will be used for] patients who are quite anemic and have struggled to continue treatment with ruxolitinib at adequate doses without needing transfusions or developing symptomatic anemia. That’s the ideal population. Certainly, you could think about using it outside of those bounds, as well. Anyone with anemia and some degree of splenomegaly symptoms could be afforded momelotinib as an option, given the concern that ruxolitinib or fedratinib treatment might drop hemoglobin [levels], pushing people into transfusion dependency.

In that anemic population, there are outstanding questions: What about patients who don’t have symptomatic splenomegaly and don’t have a ton of disease-related symptoms, but are anemic? Is this now going to be our treatment of choice for this cytopenic population? Momelotinib was nominally better than danazol [at reducing transfusion dependence], so are we going to now choose this over danazol in a patient without too many splenic symptoms? That’s tough to say right now, but you could make an argument for momelotinib in that space.

In patients who are not anemic and are being treated with ruxolitinib but need to move to a second-line agent, is [momelotinib an option] that you’re going to leverage, knowing that anemia is part of the natural history of this disease over time and that it may be reasonable to start this type of an agent earlier rather than later? There are many different areas where this could be a beneficial agent, but [its potential role in] the anemic population is very clear.

What is your main message for colleagues regarding this approval?

Momelotinib is another tool in the toolbox. [It’s approval] is another reason to differentiate and understand when and why you would use different JAK inhibitors since we now have 4 [available]. You have to understand why and when to use one agent over the other, when you’re going to switch from one to the other, when you’re going to dose modify, and which agents are best [for each case]. This is a good time to think about those questions and have a clear plan in mind. It’s great to have different options for patients, but knowing when to use them is going to ensure that we’re using them in the right way.

References

  1. 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 4, 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
  2. Momelotinib (Ojjaara) Prescribing information. GlaxoSmithKline; 2023. Accessed November 2, 2023. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Ojjaara/pdf/OJJAARA-PI-PIL.PDF
  3. Verstovsek S, Gerds AT, Vannuchi AM, et al. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023;401(10373):269-280. doi:10.1016/S0140-6736(22)02036-0

Read more

EXCEED-ET Study Evaluates Ropeginterferon alfa-2b-njf in ET

Posted on by

November 2, 2023

Lucia Masarova, MD

Lucia Masarova, MD, PhD, assistant professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the rationale of the EXCEED-ET study (NCT05482971) of ropeginterferon alfa-2b-njf (Besremi) for patients with essential thrombocytopenia (ET).

Transcription:

0:10 | The EXCEED-ET study is getting the ropeginterferon, which is the novel interferon into the space of ET. It is phase 1/2 study that gets the novel ropeginterferon in patients in North America. The patients are hydroxyurea-refractory or hydroxyurea-naive. Patients that have ET platelets over 450,000 need the therapy with some symptoms, and do not have a contraindication for interferons, which also had to be mentioned that the drugs could not be used in patients that have previous autoimmune disease, psychiatric diseases, or neurological because it could aggravate their symptoms.

0:51 | But those patients, if they would be eligible, they could be getting the full access to the drug. Also, with patients with ET, the escalation is going to be a lot faster to 250 micrograms, every other week, 350, and then 500 is the maximum dose that has been explored. However, I have to say the approval of ropeginterferon for PV had even higher dose, and the maximum-tolerated dose was not reached. This is a perfectly safe dose that we have patients on. We’re going to see how it’s going to do in ET patients.

1:25 | There is a core treatment period, which continues after the 4 weeks of escalation of up to 56 weeks. The patients will be dosed every other week with a tolerable dose. We will be monitoring the primary end points of durability of control, hematologic control, platelets less than 450, white cells less than 10. That will basically sustain 80% of 36 consecutive weeks. Then, the key secondary end points are going to include all important end points in ET patients, such as complete hematologic response, composite hematologic response, that includes control of spleen, control of symptoms, absence of disease progression, and absence of thromboembolic events. Then, it’s going to also have this exciting end point, which is basically a decline or allele burden. We’ll be checking the allo burden, what we call the molecular response, and then bone marrow morphology response.

Read more

Presentation at MPN Congress and ASH Annual Meeting Reinforce Clinical Role of ropeginterferon alfa-2b-njft

Posted on by

November 2, 2023

BURLINGTON, Mass., November 02, 2023–(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, today announced that new abstracts on ropeginterferon alfa-2b-njft will be presented during the 15th International Congress on Myeloproliferative Neoplasms (MPN Congress) in Brooklyn, NY on November 2-3, 2023, and during the 65th American Society of Hematology (ASH) Annual Meeting in San Diego, CA on December 9-12, 2023.

Key highlights from the accepted abstracts include:

  • AI-based Discovery: Application of AI technology to identify a potentially important association between myeloproliferative neoplasms (MPNs) and neurodegenerative diseases that may reflect common disease mechanisms and shared targets, including inhibitory immunoreceptors. The analysis suggests that dysregulation of specific immune checkpoints may promote chronic inflammation and thrombosis in MPNs and targeting these pathways may represent a novel approach to restoring immune and vascular homeostasis in these diseases.
  • Patient Survey: A qualitative analysis of responses to a survey distributed to MPN patients in partnership with two MPN advocacy organizations was conducted to help understand the patient experience on ropeginterferon alfa-2b-njft. In the interim analysis, themes that emerged from MPN patient responses ranged from satisfaction of observed outcomes with ropeginterferon alfa-2b-njft, management of safety concerns and comments on the ease of the injection.
  • Clinical Trial in Progress: Study design details of the Phase 2b clinical study EXCEED-ET evaluating ropeginterferon alfa-2b-njft for the investigational treatment of adults with essential thrombocythemia (ET) in the U.S. and Canada will be shared.
  • Medical Chart Review: A description of the study details for a quantitative, retrospective review of medical charts to assess the longitudinal clinical and economic burden of illness in patients with polycythemia vera (PV).
  • Investigator-led Korean study: Interim results from an independent, single-arm, open-label, multicenter study showed that with ropeginterferon alfa-2b-njft therapy and an accelerated dose titration at 12 months, 63% of participants achieved a complete hematological response, 61% achieved molecular response, as well as an overall reduction in JAK2 allele burden. The treatment was well tolerated in evaluated patients with PV.

“PharmaEssentia strives to be an essential partner to the MPN community, and these findings are a testament to the breadth and depth of the current and planned clinical and real-world evidence supporting the safety and efficacy of ropeginterferon alfa-2b-njft as a therapeutic option,” said Raymond Urbanski, M.D., Ph.D., Senior Vice President and U.S. Head of Clinical Development and Medical Affairs at PharmaEssentia. “We believe these encouraging data will help healthcare providers advance important discussions around improving care and outcomes for people living with MPNs who continue to face challenges managing their rare blood cancers.”

MPN Congress Abstract Details

  • Causal AI dissection of RNAseq datasets pinpoints connections between MPNs and neurodegenerative diseases
    • Abstract 127 – Thursday, November 2, 2023, 5:15 – 7 PM ET
  • Sharing the treatment experience of ropeginterferon alfa-2b-njft: A qualitative analysis of patient responses
    • Abstract 141 – Thursday, November 2, 2023, 5:15 – 7 PM ET
  • The clinical and economic burden of illness in patients with polycythemia vera: A retrospective medical chart audit study
    • Abstract 133 – Thursday, November 2, 2023, 5:15 – 7 PM ET
  • EXCEED-ET: A single-arm multicenter study to assess the efficacy, safety, and tolerability of ropeginterferon alfa-2b-njft (P1101) in North American adults with essential thrombocythemia
    • Abstract 137 – Thursday, November 2, 2023, 5:15 – 7 PM ET
  • A single-arm, open-label, multicenter study to assess molecular response of P1101 therapy in patients with polycythemia vera and elevated hematocrit
    • Abstract 116 – Thursday, November 2, 2023, 5:15 – 7 PM ET

ASH Abstract Details

  • A single-arm, open-label, multicenter study to assess molecular response of P1101 therapy in patients with polycythemia vera and elevated hematocrit: results from 12-month core study (New Data)
    • Abstract 4575 – Monday, December 11, 2023, 6 – 8 PM PT

Follow PharmaEssentia USA on Twitter and LinkedIn for news and updates at the meetings.

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 JAK2.1

About Essential Thrombocythemia (ET)

Essential thrombocythemia (ET) is a myeloproliferative neoplasm (MPN) characterized by an overproduction of platelets in the blood that results from a genetic mutation; data indicates a JAK2 gene mutation is present in approximately half of diagnosed patients. ET is estimated to affect up to 57 per 100,000 people in the U.S. The disease is most commonly diagnosed through routine blood work and is most common in people over the age of 50, with women 1.5 times more likely to be diagnosed than men. As a chronic, progressive disease, ET requires regular monitoring and appropriate treatment. Over time, the disease may progress into more deadly conditions such as myelofibrosis or acute leukemia.2,3

Read more

Pelabresib Generates Excitement in Myelofibrosis

Posted on by

November 3,  2023

Jordyn Sava

Multiple studies are evaluating pelabresib (CPI-0610) for the treatment of patients with myeloproliferative neoplasms (MPNs). With more data on the agent expected to be released from trials in this space toward the end of the year, Joseph M. Scandura, MD, PhD, reflected on its potential role for patients with myelofibrosis and studies evaluating the agent.

Pelabresib is an oral, small-molecule, investigational BET inhibitor. The agent works by downregulating NF-κB and signals other relevant genes involved in myelofibrosis disease pathways.

In the ongoing, global, nonrandomized, multicohort, open-label, phase 2 MANIFEST study (NCT02158858), investigators are assessing pelabresib as a monotherapy and in combination with ruxolitinib (Jakafi) in patients with myelofibrosis.1

The study is evaluating the efficacy of the JAK inhibitor combination therapy vs pelabresib alone for treatment-naïve or pretreated patient populations, and involved 4 separate cohorts. Patients with JAK inhibitor-pretreated myelofibrosis were given pelabresib, patients with ruxolitinib-pretreated myelofibrosis were given pelabresib plus ruxolitinib, patients with JAK inhibitor naïve myelofibrosis were given pelabresib plus ruxolitinib, and patients with essential thrombocythemia were given pelabresib alone.

According to data from the trial presented at the 2023 EHA Congress, by the data cutoff of July 29, 2022, 7 of the 20 patients enrolled in the study were treated for at least 6 months. Fourteen patients continued to receive pelabresib. Findings showed that pelabresib plus ruxolitinib demonstrated durable improvements in spleen volume and total symptom score among those enrolled. The confirmed complete response rate was 40% and the partial hematologic response rate was 20%, respectively.

Another study evaluating pelabresib is the ongoing, randomized, double-blind, phase 3 MANIFEST-2 trial (NCT04603495).2 Here, patients with JAK inhibitor-naïve myelofibrosis are being randomized 1:1 and treated with upfront pelabresib plus ruxolitinib vs ruxolitinib alone.

Patient enrollment in this study was completed in May 2023. Topline findings are expected to be released in late 2023.

In an interview with Targeted OncologyTM, Scandura, Weill Cornell Medicine, discussed research on pelabresib for the treatment of patients with MPNs.

Targeted Oncology: Can you discuss pelabresib and its mechanism of action?

Scandura: Pelabresib is a first-in-class oral inhibitor of BET proteins, primarily those containing the BD1 and BD2 domains. It’s being developed currently in myelofibrosis. It has been tested in other diseases, but it has shown significant activity in myelofibrosis. I believe that it’s going forward in that area and represents the first of what is potentially multiple drugs hitting these same epigenetic pathways.

What sets it apart from other agents for patients with MPNs?

Well, it’s the first drug that hits the BET inhibitors. It’s among the first epigenetic modifiers, and these are pathways that affect how genes are packaged and expressed, turned on, and turned off. In all myeloid malignancies, in fact in all cancers, epigenetic abnormalities are much more common than genetic abnormalities and exactly how to target them has been a challenge. This particular pathway has been shown to be kind of hyperactivated in myelofibrosis. This inhibitor has shown some activity, both in terms of single-agent use and in combination with standard JAK inhibitor therapy.

Can you explain some of the recent research on pelabresib?

John Mascarenhas, MD, [presented] an update of the long-term follow-up of patients treated with the combination of ruxolitinib with pelabresib–ruxolitinib being a first-in-class and standard-of-care JAK inhibitor. What he’s showing are the remarkable early responses that have been observed and are being maintained through the most recent follow-up. Then, Claire Harrison, MD, FRCP, FRCP, [presented] data on another arm of the phase 2 study where in pelabresib was added to ruxolitinib in people who are not achieving an adequate response.

I have presented an update on the translational work related to pelabresib trying to understand what some of these markers are, and these changes were observed in the bone marrow. From that standpoint, I think that’s where the excitement was generated with pelabresib. It’s 1 of the first agents that has been able to reverse fibrosis in the marrow in a sizable percentage of patients. Of course, this disease is myelofibrosis, so the idea of reducing fibrosis is appealing.

The reality of it is we don’t know, besides that kind of intuitive appeal, what it means when patients respond and have reversion of fibrosis in terms of long-term outcomes or in terms of what that goes along with our patients feeling better. [Those are] some of the other measures of response correlating with the marrow response.

What are some key takeaways regarding pelabresib and its development?

The first one is that we need to wait for the data to mature. My personal bias is all of these biomarkers are invaluable until we know outcomes such as survival or time to treatment failure or event-free survival. Until we know that, we are just kind of stuck in this circular loop of what should be, what we hope will be, what our intuitive beliefs are, but we do not really know what any of these things mean until we have those outcomes. That just takes time.

The nice thing is there are a number of phase 3 studies, randomized trials, collaborative studies. MANIFEST-2 is a randomized phase 3 study, and that will allow us to address and follow up on some of these findings, and hopefully get to those answers about whether or not these changes that we’re observing in the short-term are predicting these long-term beneficial outcomes. It just takes time for that data to mature.

REFERENCES:
Passamonti F, Patriarca A, Knapper S, et al. Pelabresib (CPI-0610) monotherapy in patients with high-risk essential thrombocythemia refractory or intolerant to hydroxyurea: preliminary results from MANIFEST study. Presented at: 2023 EHA Congress; June 8-11,2023;Frankfurt,Germany. Abstract S168.
Harrison CN, Gupta VK, Gerds AT, et al. Phase III MANIFEST-2: pelabresib + ruxolitinib vs placebo + ruxolitinib in JAK inhibitor treatment-naive myelofibrosis. Future Oncol. 2022;18(27):2987-2997. doi:10.2217/fon-2022-0484

Read more

 

Patients on Medicaid Disproportionately Affected by Drug Shortage

Posted on by

November 2, 2023

Brielle Benyon

A new survey conducted by the American Cancer Society Cancer Action Network (ASC CAN) found that many patients in active cancer treatment reported being affected by the ongoing drug shortage, with patients insured by Medicaid being disproportionately affected.

“One of the most salient insights that we received here is that this is not affecting everybody equally,” Mark Fleury, policy principal for the ACS CAN said in an interview with CURE®.

A higher percentage of patients on Medicaid were affected by the cancer drug shortage than those who were insured by their employer.

The survey, which was conducted in September 2023, included survey responses from 1,222 patients and survivors of cancer who have been diagnosed with or treated for cancer within the last seven years. The findings showed that while 10% of overall patients in active treatment were affected by the chemotherapy shortage, patients insured by Medicaid were more impacted by it, with 18% stating that they were affected.

“We have a very tight supply chain. There’s really no buffer there, so every vial that’s made has to be distributed,” Fleury explained. “There are (cancer treatment) sites that are large enough to have someone keep an eye on shortages, but not every institution has that. … It seems that institutions that are maybe smaller or have fewer resources or personnel to be chasing down these drugs are the ones that are the most impacted. And institutions with less resources oftentimes are serving patients with less resources as well.”

Fleury mentioned that cancer drug shortages put unnecessary stress on patients and their families during an already stressful time, and patient-provider communication is key.

“Patients (should have) individual conversations with their providers about how to move forward, and obviously every patient and every cancer type is different. Some have appropriate solutions, and some don’t.”

Regardless of insurance type, the most common way people were affected by the drug shortage included:

  • Delayed or missed treatment (reported by 45% of respondents who were affected, including 38% of this population who faced delays of one month or longer)
  • Using an alternate drug (23%; with 68% reporting that they and their medical teams were not able to find an effective substitute)
  • Faced difficulty using their insurance to fill a prescription related to the shortage, such as delays in covering an alternative drug (35%)
  • Continued the medication with a dose change (6%)

The survey, which was published in October, also included quotes from patients who participated. One individual said, “My doctor’s office only gets enough for one patient a month. I’m currently set to get mine in over six months.” Another person said, “(The shortage) has extended my treatment, which adds to the stress level and horrible side effects.”

However, some individuals — approximately 40% of those surveyed — said that their issues related to cancer drug shortages have since been resolved and their drug is now available to them.

“I think we may be slowly moving away from reducing the number of patients who aren’t able to get the drugs that they need. But I think we’re just going up to that slightly better level where the system is still super fragile. And any additional disruptions … could bring us back and patients not getting them,” Fleury said, mentioning that the ACS CAN is investigating solutions that can fix this problem in a more robust way.

“There (are) short term fixes (for) people who need (cancer drugs) today. … It took us years and even decades to get here. It’s going to take us years to get us out. So we’re looking at both short, shorter and long-term solutions to try and get us away from the brink where we’ve been living, frankly, for quite a while.”

Read more

Early to Bed, Early to Rise

Posted on by

By Natalie Giocondo

“Early to bed, early to rise, makes a man healthy, wealthy, and wise.” -Benjamin Franklin.

As the last few leaves of autumn fall, and we barrel headlong into the busyness of the holidays, let’s take a moment to welcome the shortening of days and changing seasons. Flowing from a time of harvest to a time of suspension Winter presents us with the opportunity to pause. Just as the animals hibernate and the plants go dormant, we too are invited by the late sunrises and early sunsets to tuck in for some deep relaxation and sleep.

Getting a good night’s rest promotes physical health and overall well-being; unfortunately, it can be a challenge and maybe particularly challenging for MPN patients. According to the National Institutes of Health (NIH), sleep affects every system in the body, and lack of sleep correlates with several issues of interest to the MPN community, including high blood pressure and cardiovascular disease. The NIH also suggests that insomnia is an unmet need in communities with chronic hematological cancers. In 2017, a study conducted by Dr. Krisstina Gowin echoed that unmet need when 52.1 % of her MPN participants reported trouble staying asleep, and another 33.7% said they had difficulty falling asleep, while 31.2% mentioned having insomnia. 

Here are some tried and true healthy sleep habits:

  • Stay on a sleep schedule. Go to bed and rise at the same time each day. I, for one, begin heading to bed earlier once the cold sets in and the roosters are crowing a little later in the morning. 
  • Create an environment for sleep. Dark, quiet, cool, and without electronics works best. 
  • Get enough exercise during the day. If you don’t already have an exercise routine, I highly recommend Justin Grinnell’s Moderate-Impact webinar to get you started. 
  • Avoid stimulation. This could be anything from caffeine to nicotine to watching the news or engaging in heated conversations too close to bedtime. 
  • Eat early. This point cannot be understated! Some patients with MPNs report digestive issues that interfere with sleep. Giving your body plenty of time to process before heading to bed may be worth a try.

Yoga Nidra

A less well-known practice to encourage deep rest and cultivate sleep is yoga nidra. The words yoga nidra mean yoga (to yoke) and nidra (to sleep). It brings up images of a little yogi cowboy lassoing sleep, or a sleep herder. This practice was brought to the US in the 1960s by Swami Satchidadnanda and popularized by practitioners like Nischala Joy Devi (Deep Relaxation), and Dr. Richard Miller (iRest Yoga Nidra).

The practice requires the practitioner to lie in a comfortable resting position while a guide verbally takes them on a gentle journey through 6 phases of meditation: preparation, intention, rotation of consciousness, breath awareness, sensation awareness, visualization, and dropped mind awareness.

While not studied in the MPN population, studies on yoga nidra have suggested benefits such as reduced perceptions of pain, positive effects on blood pressure, pulse, and respiration rates, reduction in erythrocyte sedimentation (which detects the level of inflammation in the body), and has cured chronic insomnia in some people. 

If you are curious about yoga nidra and would like a little taste, please join me on Thursday, November 16th at noon ET, when we will host a 30-minute guided yoga nidra practice. 

 

Supporting the Patient’s Psychosocial Needs Throughout MPN Treatment

Posted on by

October 31, 2o23

Rebecca Testi, MSN, APN, APN-G

Patients with myeloproliferative neoplasms (MPNs) — a rare form of blood cancer — may lack specific met needs when it comes to psychological care. Providers and caregivers can start by validating patients with MPN to help diminish psychosocial needs, according to Rebecca Testi, MSN, APN, APN-G, Hackensack Meridian Health.

“I think education is really key with the patients, you as the nurse or nurse practitioner clinician really need to be able to tell patients, the depression is a side effect of the disease itself. Not you necessarily being sick, but truly like an underlying disease process. So I think it all starts with really good education, about disease process, treatment, support options, things like that,” explained Testi.

With patients who have MPNs, psychosocial help can be rare, causing patients to lack proper resources. Getting patients to normalize utilizing help can go unmanaged.

“I think we as providers could definitely be better about addressing it, explained Testi, who added that although its normal for patients to feel this way, it is important to find ways to help patients manage it so they can live a more normal life.

“Most cancer centers have really good social workers on staff that are designated to that particular division,” she said. “Where I work, we have dedicated social work for all liquid tumor patients, and most institutions will be able to connect you with a peer-to-peer support group. If patients agree, we’ll often connect one MPN patient with another who’s willing to have their information shared so that they can talk to each other share their feelings.”

Testi also highlighted the importance of caregiver support groups.

“Another thing that’s really important is caregiver support groups,” she said. “Their families can interact and share how having a loved one with this defeat disease affects them. It is often just as hard on the family members and caregivers as it is on the patient.”

Read more

DISC-0974 by Disc Medicine for Myelofibrosis: Likelihood of Approval

Posted on by

October 28, 2023

DISC-0974 is under clinical development by Disc Medicine and currently in Phase II for Myelofibrosis. According to GlobalData, Phase II drugs for Myelofibrosis have a 40% phase transition success rate (PTSR) indication benchmark for progressing into Phase III. GlobalData’s report assesses how DISC-0974’s drug-specific PTSR and Likelihood of Approval (LoA) scores compare to the indication benchmarks.

Smarter leaders trust GlobalData

GlobalData tracks drug-specific phase transition and likelihood of approval scores, in addition to indication benchmarks based off 18 years of historical drug development data. Attributes of the drug, company and its clinical trials play a fundamental role in drug-specific PTSR and likelihood of approval.

DISC-0974 overview

DISC-0974 is under development for the treatment of chronic inflammation and hematological disorders such as anemia of chronic disease, anemia in chronic kidney disease, Iron refractory iron deficiency anemia (IRIDA), myelofibrosis, chronic idiopathic myelofibrosis (primary myelofibrosis), post-essential thrombocythemia myelofibrosis (post-et mf), post-polycythemia vera myelofibrosis (ppv-mf) and myeloproliferative disorders. The drug candidate acts by targeting hemojuvelin. It is administered through intravenous and subcutaneous routes.

Disc Medicine overview

Disc Medicine, formerly Gemini Therapeutics Inc, is a clinical-stage biopharmaceutical company that specialises in the discovery, development and commercialization of novel treatments for patients with severe hematologic disorders. The company pipeline includes bitopertin for the treatment of erythropoietic porphyrias, including erythropoietic protoporphyria and X-linked protoporphyria and Diamond-Blackfan Anaemia, or DBA; DISC-0974 for the treatment of anaemia of myelofibrosis and anaemia of chronic kidney disease, or CKD; and MWTX-003 for the treatment of polycythemia vera, or PV, and other hematologic disorders. The company’s preclinical programmes consist of DISC-0998, which is used to treat anaemia brought on by inflammatory disorders. Disc Medicine is headquartered in Cambridge, Massachusetts, the US.

Read more

Patients With MPN-Related Fatigue ‘Know Their Bodies Very Well’

Posted on by

October 27, 2023

Ashley Chan

Patients with myeloproliferative neoplasms (MPNs) may experience a number of symptoms, with fatigue being one of them.

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

MPN-related fatigue can take a toll on a patient’s quality of life, notably because of the change in the blood’s consistency.

“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, because your condition is unchecked, then a lot of times it can actually be debilitating,” Patrick Buxton, a clinical nurse coordinator in the hematology department at Fred Hutchinson Cancer Center in Seattle, Washington, said during an interview with CURE®.

“(Patients are) not having the energy to go out and work, participate in family events and just (engage with) life in general. And they just don’t really feel well overall,” Buxton said. “And so, it’s 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 (a patient’s) blood counts become so high that (their) blood basically becomes a sludge, (they) definitely feel it. And it can cause a whole lot of problems centered around fatigue, but not just fatigue. It can cause a lot of inflammation issues.”

To work through the weight of fatigue, Buxton urged patients to hydrate, eat nutritious food and exercise.

“Especially with MPN, patients maintaining good hydration and adequate nutrition is very important. Because once (patients) kind of get stuck in a downward spiral, it can be very hard to get out,” he noted. “So, making sure that … patients are trying to get a good amount of exercise daily, even if it’s just getting out of bed, pushing (themselves) a little bit each day to try to get that energy going again and making sure that (they) eat and drink enough to keep going.”

Staying hydrated is essential for patients with MPNs, Buxton emphasized.

“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 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.’”

For patients with MPNs who experience fatigue, Buxton advised them to have open communication with their care teams.

“That line of communication is very important. And even if the patients don’t think it’s important, they know their bodies very well. So, if something is not working right, communicate that to the team,” he said. “And know that it really is a lot of teamwork with the nurses, the patients, the doctors, that the patient is an integral part of the team; without the patient, we wouldn’t be here.

“So, know that (patients are) the center of all of this, and we are here to help, but if (they) don’t report these issues (to us) and just let them be then we won’t know. So, with that information, be a good self-advocate, because that’s how (they’re) going to get better care is being an active participant. Don’t let small things go because sometimes small stuff adds up to something big. And especially with fatigue — patients know their bodies well. So, follow up. Make sure that you are getting the care that you need.”

Read more

Understanding the Three Types of MPNs

Posted on by

October 26, 2023

Darlene Dobkowski, MA

Understanding which of the three types of myeloproliferative neoplasms (MPNs) a patient has can help guide them to receive the appropriate treatment and management of the disease.

Of note, MPNs are a group of rare blood disorders where the bone marrow creates too many blood cells. This can lead a patient to have an imbalance of red blood cells, white blood cells and platelets, all of which can lead to several symptoms. These can include feeling tired, issues with clotting or bleeding and potentially an enlarged spleen.

Unfortunately, the number of patients diagnosed with MDS in the United State each year is not exactly known, according to the American Cancer Society. The organization notes that estimates start at 10,000 and can increase from there. The risk for MDS increases as a patient ages and diagnosis of the disease is uncommon before age 50, according to the American Cancer Society, with most patients diagnosed in their 70s.

Each of the three types of MPNs have their own set of symptoms and management strategies, highlighting the importance of knowing which disease a patient has.

Polycythemia Vera

In patients with polycythemia vera, the bone marrow produces too many red blood cells, which typically carry oxygen throughout the body. This overproduction of red blood cells can thicken a patient’s blood, leading to issues like blood clots and an increased risk for stroke.

The exact cause of polycythemia vera is often not clear, but it is typically related to genetic mutations in the bone marrow cells, particularly in a gene called JAK2. Diagnosis is typically made through blood tests that reveal elevated red blood cell counts, hematocrit levels and the presence of the JAK2 mutation.

Patients with polycythemia vera may experience symptoms like fatigue, headaches and redness or itching of the skin. Treatment for this type of MPN often involves medications and occasionally procedures to reduce the number of red blood cells a patient’s body makes. In particular, treatment for polycythemia vera may include phlebotomy (removing excess blood), medications to reduce blood cell production and management of symptoms and complications.

Essential Thrombocythemia

With essential thrombocythemia, the bone marrow creates too many platelets, which are the cells that help blood clot. Too many platelets can lead patients to experience clotting and bleeding issues. In particular, blood may clot too easily, which can block blood vessels and cause issues like strokes or heart attacks. Paradoxically, patients may also experience bleeding problems because the blood doesn’t clot properly in some cases.

The exact cause of essential thrombocythemia is not well understood, but it is often associated with genetic mutations, particularly in genes like CALR, JAK2 or MPL.

Some patients with essential thrombocythemia may not have any symptoms or they may experience things like headache, dizziness or red spots on their skin.

Patients are recommended to work with their care team to manage the disease and potentially reduce the risk for complications, both of which may be achieved with medications or procedures like plateletpheresis (when platelets are filtered from a patient’s blood through a machine) to control the number of platelets in the blood.

Myelofibrosis

In patients with myelofibrosis, the bone marrow becomes scarred and experiences difficulty in creating enough healthy blood cells, which may lead to fatigue, anemia, an enlarged spleen and an increased risk for infections. Symptoms may also include pain and early satiety, or feeling full even when the patient has not eaten much.

Similar to essential thrombocythemia, myelofibrosis may also be linked to specific genetic mutations like CALR, JAK2 or MPL.

A patient’s care team may manage myelofibrosis with blood transfusions to manage anemia, supportive care to address symptoms, medications to reduce the size of the spleen or, if necessary, a bone marrow transplant.

Read more