Category Archives: Pediatric MPN

Clinical Features and Long-Term Outcomes of a Pan-Canadian Cohort of Adolescents and Young Adults with Myeloproliferative Neoplasms: A Canadian MPN Group Study

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James T. England, Natasha Szuber, Shireen Sirhan, Tom Dunne, Sonia Cerquozzi, Madeleine Hill, Pierre J. A. Villeneuve, Jenny M. Ho, et al.

Abstract

Myeloproliferative neoplasms (MPNs) are a group of chronic hematologic malignancies that lead to morbidity and early mortality due to thrombotic complications and progression to acute leukemia. Clinical and mutational risk factors have been demonstrated to predict outcomes in patients with MPNs and are used commonly to guide therapeutic decisions, including allogenic stem cell transplant, in myelofibrosis. Adolescents and young adults (AYA, age ≤45 years) comprise less than 10% of all MPN patients and have unique clinical and therapeutic considerations. The prevalence and clinical impact of somatic mutations implicated in myeloid disease has not been extensively examined in this population. We conducted a retrospective review of patients evaluated at eight Canadian centers for MPN patients diagnosed at ≤45 years of age. In total, 609 patients were included in the study, with median overall survival of 36.8 years. Diagnosis of prefibrotic or overt PMF is associated with the lowest OS and highest risk of AP/BP transformation. Thrombotic complications (24%), including splanchnic circulation thrombosis (9%), were frequent in the cohort. Mutations in addition to those in JAK2/MPL/CALR are uncommon in the initial disease phase in our AYA population (12%); but our data indicate they may be predictive of transformation to post-ET/PV myelofibrosis.

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Goals of Managing Cytopenic Myelofibrosis in Younger Patients

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Targeted Oncology Staff

During a Targeted Oncology™ Case-Based Roundtable™ event, Naveen Pemmaraju, MD, and participants discussed the role of JAK inhibitors in managing myelofibrosis particularly in younger patients who may receive allogeneic stem cell transplant. This is the first of 2 articles based on this event.

CASE SUMMARY

A 62-year-old man presented to his primary care physician (PCP) with symptoms of fatigue, night sweats, and increased bruising​. He had a history of type 2 diabetes, hypercholesteremia, and hypertension​. The PCP noticed lower hemoglobin concentration (11 to 9.5 g/dL) and platelet count (350 × 109/L to 195 × 109/L) from a previous annual physical examination. ​He was referred to a hematologist/oncologist for consultation and evaluation​. ​

Two months post-PCP visit, he went to a hematologic oncologist. Exam findings included a spleen 5 cm below left costal margin, fatigue and night sweats worsening​, bone pain​, hemoglobin of 8.7 g/dL, and platelet count of 135 × 109/L ​. He was diagnosed with primary myelofibrosis (MF); ​bone marrow fibrosis of grade 2, with 35% bone marrow blasts. He had a history of squamous cell carcinoma of the skin​.

Molecular analysis showed a JAK2 V617F mutation and normal cytogenetics​. Blood smear reveals leukoerythroblastosis: 1% blasts by manual count/flow cytometry​. His ECOG performance status (PS) was 2. ​

DISCUSSION QUESTIONS

  • In your practice:​
    • When do you initiate therapy for a patient with MF? ​
    • What is the importance of symptom control? ​
    • How important is it to initiate therapy early? ​
    • When do you start JAK inhibitor therapy?​
    • Do you choose your initial JAK inhibitor based on patient symptoms? ​

DAI CHU LUU, MD: My standpoint is that a 62-year-old is still young. I have transplant physician within 5 miles of my practice. I would definitely send to a transplant physician…see what they have to say, and then follow up on the recommendations. Usually they’ll give recommendations and then I’ll act on them. Whenever things get tough, I’ll send it to them to establish care.

NAVEEN PEMMARAJU, MD: That’s great. What do you think about JAK [Janus kinase] inhibitor therapy? [Would you use] monotherapy as standard of care up until the transplant?

LUU: Yes.

PEMMARAJU: If the platelets are below 50 × 109/L, what we’ve been doing [in the past] is either giving ruxolitinib [Jakafi] or low-dose ruxolitinib. Maybe you’re doing something different. Has anyone yet prescribed the new agent, pacritinib [Vonjo], which is approved in this lower than 50 × 109/L setting?

SRIKAR MALIREDDY, MD: I have prescribed pacritinib. I had a patient on ruxolitinib for the longest time and then eventually the disease progressed and I could not do any more administration of ruxolitinib. He’s been on [pacritinib] for at least 7 to 8 months.

PEMMARAJU: [Was there] any diarrhea or bleeding events? Or has it been well tolerated?

MALIREDDY: There were no [tolerability issues]. I was very careful with starting with a low dose, and then ramping up. We also watched the platelet counts, and so far…[he has] 30 × 109/L to 40 × 109/L platelets.

PEMMARAJU: What dose did you start? Did you start at 100 mg? Because the approved dose is 200 mg twice daily.1

MALIREDDY: Yes, I started at 100 mg. [Since] he was tolerating it, he is at the maximum dose right now. He’s at 200 mg.

PEMMARAJU: That’s a great story. Did you have any difficulty getting it through insurance or through your specialty pharmacy?

MALIREDDY: This was one of the patients…who initially got azacitidine [Onureg] in combination with ruxolitinib. He was on a clinical trial for that.

PEMMARAJU: For the ruxolitinib/azacitidine trial [NCT01787487]?

MALIREDDY: Yes, exactly. He had some severe cytopenias, myelosuppression, and all that [on the clinical trial]. Eventually, the cytopenias progressed, then [he started on pacritinib]. I didn’t have any issues with getting approval.

PEMMARAJU: That’s great. The combined answer from both of you is the cutting-edge state of the art, which is offering a JAK inhibitor [while] trying to get to [allogeneic stem cell] transplant. We all assume—and it ends up being correct a lot of the time in our patients with myeloproliferative neoplasms as opposed to leukemia or some of the other [disease] states— what happens is [patients have an] ECOG PS of 2 to 3, but they have PS of 0 to 1 after the initiation of JAK inhibitor. With ruxolitinib, it’s usually about 3 months that you see it. After 1 week to 1 month, you start feeling great; by month 2 and 3 is the plateau.

DISCUSSION QUESTIONS

  • What are the therapeutic goals of therapy for a patient with aggressive disease? ​
  • When do you consider clinical trial enrollment?

PEMMARAJU: All of us in the field are thinking about the significance of cytopenic MF. It helped lead to the drug approval for this JAK inhibitor [pacritinib], which is great because I have had several similar situations in prescribing it. It’s a very well tolerated drug. But…how frequent is this? Most people in our field think that the cytopenias are treatment related or they happened later on. That is common. But thrombocytopenia and anemia can occur in a quarter or more of our patients at baseline. Some of these patients present…with fairly advanced disease. How often do you encounter a baseline platelet count of less than 50 × 109/L at any point in the myelofibrosis trajectory? And before pacritinib…what were you giving these patients if you had to treat them?

JAGATHI CHALLAGALLA, MD: [I would give] low-dose ruxolitinib, or if they’re transfusion independent, just observation.

PEMMARAJU: Yes, exactly, [or] sometimes we would…give danazol or steroids. Now we know that delivering suboptimal doses is leading to suboptimal outcomes.2 If you’re not reducing the spleen, not improving the symptoms, patients won’t do as well. The benefit of pacritinib…is you can give the full dose of the drug. We heard 1 story of being very cautious, but you can prescribe it as the 200 mg dosing even in the thrombocytopenic setting.1 Just watch out for diarrhea, usually resolved in the first 4 to 6 weeks. It’s usually well managed, but you and the patient need to know about it. There was some concern about cardiac bleeding events…particularly for patients on anticoagulants, but it is a fairly well-tolerated drug.

Say the patient is 82 years old, and transplant is off the table. [For] low platelet count, you’re giving a low dose of ruxolitinib, [or] you’re giving pacritinib…or fedratinib [Inrebic]. What is the goal of therapy in a patient who’s a non-transplant candidate for whom you’re giving a JAK inhibitor?

ANANTH ARJUNAN, MD: For the patient, the symptom improvement is critical. Along with that getting the spleen [size] down is important, not just for survival benefit, but for the patient to feel better. In terms of discussing treatment options, we go through the different JAK inhibitors, typically based off comorbidities, and then their [blood cell] counts. I haven’t found a reason to use fedratinib. It’s usually a question of ruxolitinib or pacritinib. For clinical trial enrollment, any time is appropriate, although we might wait until they become JAK inhibitor resistant, although you have some options recently with momelotinib.

References:

1. Vonjo. Prescribing information. CTI BioPharma Corp; 2022. Accessed August 29, 2023. https://tinyurl.com/yxjnn7yu

2. Maffioli M, Mora B, Ball S, et al. A prognostic model to predict survival after 6 months of ruxolitinib in patients with myelofibrosis. Blood Adv. 2022;6(6):1855-1864. doi:10.1182/bloodadvances.2021006889

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A Mother’s Story: When Your Child is Diagnosed with an MPN

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No one can prepare you for a cancer diagnosis of a child. Our daughter was four years old and began to complain about headaches. I assumed it was her eyes and made an appointment with an optometrist. Her sight was perfectly normal. A visit to her pediatrician lasted an hour with little insight, only suggestions to watch her diet, limit TV time and give her lots of water. She rarely watched TV and carried water with her throughout the day. Our diet doesn’t include sugar except from fresh fruit and we don’t eat boxed or canned food. I wasn’t optimistic. Eventually, her headaches became more severe on occasion, similar to migraines. We were sent to a neurologist. He requested blood work after she underwent an MRI. Thankfully, the blood work identified the problem-ET or essential thrombocythemia. We had never heard of it and had no idea what this meant for the future. A hematologist became our savior. With the proper diagnosis and medication, our daughter began to feel better, albeit a few side effects from the meds. Yogurt is a staple to help with GI issues, and a nap and early bedtime help fatigue. Yes, our little girl had what I would call fatigue. Our lives have changed but we do not let her ET control us. We control her ET. We manage her diagnosis as part of our daily lives as we would manage any other chronic disease. That is not to say it’s been easy. We have our moments of fear and doubt, but that doesn’t last as long as it used to. We keep very good records of her doctor visits, her blood levels and her overall health. We ask how she is feeling and pay attention to any changes that could be due to her ET. She is now 12 and enjoying a normal childhood. We are looking at Interferfon as a possible “next protocol,” if we think it will be better for her.  We stay informed and are very pleased to see all of the clinical trials and new drugs on the horizon. It’s easy to say don’t panic if your child is diagnosed with an MPN. I would simply say, gather the facts, stay informed, be the voice they cannot be, and remember to take good care of yourself.

Click here to learn more about Pediatric and Young Adult MPNs

Special Interview: Living with an MPN in Childhood

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Diagnosed at age seven with Essential Thrombocythemia, Portia shared her story at the 2nd Annual Pediatric & Young Adult MPN Patient Program.

Portia, a young adult MPN patient, shared her story at the 2nd annual Pediatric & Young Adult Program

Do you remember experiencing any symptoms?

I had occasional nosebleeds that would last about twenty minutes or so. But over time, the time decreased to about ten minutes. I also experience fatigue, especially when I’m sick, all I do is sleep to try and regain any energy. Also, I’m very active and I play competitive squash, so I do experience fatigue more than an average person.

How do you cope with essential thrombocythemia (ET) symptoms and/or side effects from Hydroxyurea?

I’m very lucky that I don’t really experience too many symptoms, but I usually push through any pain that I have since I’m such a wimp about medication. I have not had any side effects from Hydroxyurea. For fatigue, I don’t take any other medication, I pretty much just work hard and try to be smart about how I utilize my energy. When playing squash, I work extra hard to make up for my fatigue, but if I really can’t breathe due to lack of oxygen, I will talk to my coach and ask for a small break to recuperate. Most coaches are very reasonable and will allow a break.

Has ET curtailed your involvement in school activities?  Sports?

When I was younger, elementary and middle school age, I would occasionally have to miss school for lab appointments, so I would have to make up work. One symptom of ET is fatigue, so I do have to deal with that in sports. But I also have Hemoglobin H, which I believe has a bigger impact on my fatigue in sports than ET. But overall, I still go about my life and continue to do the things I love.

How do you explain what you have to your friends?

As I’ve gotten older, I’ve done a lot more of my own research to further understand my condition, but to my friends, I explain that I have way too many platelets, which help clot your blood when you get a cut, and because of that, I bleed for longer.

What advice would you give other younger individuals with an MPN when peers say they don’t look sick or they’re faking?

I would tell them to do their best to ignore their hateful comments and try to explain their condition by telling them it’s something internal rather than external, that’s why they don’t appear sick. And most important, find friends who won’t judge you, and people who do, clearly aren’t your real friends, for real friends should accept you no matter what.

You are very energetic and positive, when you reach out to others your age who aren’t feeling well, what do you say to encourage them?

First, I would listen to their concerns and possible issues, and then I would tell them to keep their head held high and know that it does get better. This is just a phase and eventually, the negative parts will fade away. Also, it’s very important to know who your close friends are and be able to talk to them since many kids would rather talk to their friends rather than a parent or even a doctor since it can be intimidating. I would also say, take one day at a time and find joy in the little things, whether it’s going for ice cream or just taking a nice walk.

If you could wave a wand and change one thing in the world of MPNs, what would you change?

Personally, I would change the medicine. I really hate swallowing pills, so I would much prefer something fun to eat or drink as my medicine. I’m also very strange and would much rather have the medicine get injected into me, which I know is an option, but the majority of people aren’t a big fan of needles.

 

 

 

A Parent’s Story: Navigating the Health Insurance Maze

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By Sarah W.

Sarah is a member of MPN Advocacy & Education International’s Patient Advisory Council

I know there are good people who work at insurance companies, however, some are the bane of my existence. Every month I gear up for the fight to get my son, Jedi, his medicine. Jedi has an MPN. My hope is that my journey can be used to make this process easier and better for other patients and their families.

Hydroxyurea was the initial drug prescribed for my son. It wasn’t a difficult drug to get filled, even though it was a little overwhelming walking my son through the adult oncology unit at MD Anderson Cancer Center, to the “specialty pharmacy.” It was frightening for him to see adults that look so sickly skinny and with their bald heads from their treatments. However, the real frustration began when he was put on Pegasys. MD Anderson tried to call numerous pharmacies to his prescription filled, but they were unable to find a pharmacy that had it in stock. So we left the hospital with a handwritten script in search of the drug.

Read tips from Speciality Pharmacist/MPN Patient Jennifer Powers w/ links to treatment assistance programs

At that time, we were insured by United Health Care. This was my first introduction to a specialty drug. For background purposes, specialty drugs are a recent designation of pharmaceuticals that are classified as high-cost, high complexity and/or high touch, such as injectables. A chemotherapy that is administered orally, like Hydroxyurea, is covered as part of a normal prescription. A chemotherapy that is administered as a subcutaneous (jiggly fat) shot, like Pegasys, is not. In other words, it comes out of your deductible. For us, that means we owed approximately $4,000 for the first month of Pegasys. We had to prove to the insurance company that Pegasys had been approved for polycythemia vera. This was done by producing a memo my husband found on the internet from United Health Care specifically stating Pegasys was approved for polycythemia vera.

Then, our insurance was switched to Blue Cross Blue Shield of Texas (BCBSTX). (I will skip the conversation about trying to get our member number early so I could start the pre-approval process.  I had been told in a Facebook group that it took about six weeks to approve Pegasys with BCBS. This was cause for concern because we could only get four weeks of medicine at a time.)

I started the pre-approval process with BCBS after we received a member ID number the first week of January. As expected, Pegasys was initially declined.  In the state of Texas I should be able to submit an emergency appeal and get a response in three days, but I had to get the appeal submitted first.  It is very difficult to get the appeal started. Not to mention that BCBSTX outsources the pharmaceuticals to Prime.

After a few weeks of deep frustration and the looming possibility we could run out of his medication, I finally posted the following on Blue Cross Blue Shield of Texas Facebook page:

January 15, 2019. Your appeals process is TERRIBLE. I have spent HOURS trying to figure this out. I have a 10 year old with CANCER. His medicine is out next week. I have to get it from a specialty pharmacy. His doctor called BCBS yesterday (a number I got after spending TWO HOURS on the phone last Friday) and was told that he has to wait 7-10 business days to start the process. Today I received a NEW peer-to-peer phone number. Does this start the process? No, it sets up an appointment for our doctor to talk to your doctors. Just to give you an idea. This medicine controls platelets. If his platelets go up he could have a heart attack, stroke, embolism for example. You can see my concern. My next steps are to ask my doctor to call AGAIN to START the appeals process – you know the one he tried to start yesterday? I will also have on my TO DO list to file a complaint with Texas Department of Insurance, contact my state Senator and Representative. Thank you for making this such a HARD process. Oh, by the way, the National Comprehensive Cancer Network, other BCBS insurance (different states), United Healthcare ALL have approved this medicine for his diagnosis

 I received a phone call from BCBSTX within 24 hours of posting this. I was told I had made it to the “special escalation” team because I posted on social media. On one hand, I am grateful he was approved. On the other hand, I am sad that this is what it took. I think it also helped that I had gathered the information to make it easy for them to approve. I had whitepapers, Jedi’s medical records and the details from the National Comprehensive Cancer Network. (Click here to view).

I wish I could say this was the end of the drama. But this is a story for another day. Just writing this was overwhelming. I can’t imagine what people who are sick go through. I am the caregiver, not the patient. I do not have chemo brain and I am exhausted by the process and the stress and anxiety to ensure my child receives his treatment. I hope this information will help other families move through the process a little more smoothly and I will continue to write about the trial and tribulations I experience on my website.

View Videos from the MPN Pediatric & Young Adult Program in 2018