Oh Discusses Goals of Treatment in Patients With Cytopenic Myelofibrosis

Peers & Perspectives in OncologyNovember II, 2023
Volume 1
Issue 9
Pages: 33

During a Targeted Oncology™ Case-Based Roundtable™ event, Stephen T. Oh, MD, PhD, discussed with participants when they would use pacritinib for patients with thrombocytopenia related to myelofibrosis.

Stephen Oh

Stephen T. Oh, MD, PhD (MODERATOR)

Cochief, Division of Hematology

Associate Professor

Department of Medicine

Washington University School of Medicine

St Louis, MO

EVENT REGION Illinois and Indiana

PARTICIPANT LIST Sunil Babu, MD | Neel Shah, MD | JoMel Labayog, MD | Isoken Koko, MD | Olusola Ogundipe, MD | Lisa Baddi, DO | Nishant Poddar, MD


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, hypercholesterolemia, and hypertension. His PCP noticed lower hemoglobin concentration (11-9.5 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 hematologist/ oncologist. Examination 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 and 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 revealed leukoerythroblastosis: 1% blasts by manual count/flow cytometry. His ECOG performance status was 2.


  • What are the therapeutic goals for a patient with aggressive disease?
  • How do you discuss treatment options with your patients?
  • When do you consider clinical trial enrollment?

OH: Talking about patients with some degree of cytopenia, what are your goals? Are we focused on symptoms? Are we focused on potentially prolonging life?

I’m curious to hear all your perspectives on the role of clinical trials…. From my experience over the past decade or so, although initially…many patients were referred to us [for trials] before any treatment started, nowadays, they often have been on ruxolitinib [Jakafi] and then sent to us later on.

BABU: The available drugs don’t add [significantly] to overall survival. [The goal is] essentially aiming for symptom relief in a patient who’s having a lot of constitutional symptoms, including splenomegaly-related issues. [In terms of] picking the right drug, we have a few choices now compared with a few years ago. In someone with lower platelet [counts], pacritinib [Vonjo] seems to be a better choice than the first-generation medications, although it also does cause thrombocytopenia and other issues.1 [However, the goal is] management of constitutional symptoms [because] there are no data to support survival.

If the patient can tolerate the drug even with those modifications and if we see benefits in that individual patient, then treatment is continued. If the patient can’t tolerate it or we’re not seeing any effectiveness, in a younger patient, we’ll try to reach out to centers that have a trial.

SHAH: If the patient’s not going to be eligible for any sort of [hematopoietic stem cell] transplant, that’s pretty much the only time I refer [for clinical trial], otherwise…this patient’s platelet count is less than 50 × 109/L, [so] I’d probably start pacritinib. [Is there] any new trial with a drug that’s better than what we have?

OH: There are numerous clinical trials in myelofibrosis for all kinds of patients. There are a variety of combination studies, including some that are looking at up-front combinations with ruxolitinib for treatment-naive patients. There are those looking at add-on therapies in [patients] who have a sub-optimal response to ruxolitinib. There are studies looking at the patients who are post JAK [Janus kinase] inhibitor. There are studies for patients with low platelets, or that at least include patients with low platelets.

I don’t think every patient should be enrolled in a clinical trial now that we have more than 1 option commercially available. We have a variety of potential options for these patients, and it is not…wrong to explore those available options and reserve clinical trials if those end up being not effective or [are] in some way problematic.

LABAYOG: Do you ever use any of the thrombopoietin [receptor agonists] for refractory thrombocytopenia, [such as] romiplostim [Nplate] or eltrombopag [Promacta]?

OH: The short answer is no, for 2 reasons. One is…it may not be effective anyway. [Then the data are] a little mixed, but there is potential for worsening of fibrosis with some of these agents. Those 2 things make it a nonstarter. In my experience, they’re not used in patients with myelofibrosis.


  • What are your reactions to the efficacy and safety data from the studies of JAK inhibitors?
  • Where do you see pacritinib fitting into your treatment plans?
  • How should patients be counseled about receiving a JAK inhibitor, and specifically for pacritinib?

OH: What are your reactions to the data? Where do you see pacritinib fitting into your treatment plan, and how should patients be counseled about receiving a JAK inhibitor, in particular pacritinib?

KOKO: The efficacy and the safety profiles are quite encouraging, especially the safety profile. Taking all this information into consideration, it is something I would consider as the first line in all my primary myelofibrosis cases, and even secondary myelofibrosis. In looking at the efficacy, does it also control constitutional symptoms?

OH: The data indicate yes, there clearly is symptom response with the pacritinib.2,3 Is it comparable to what you might expect of ruxolitinib or another JAK inhibitor? In the PERSIST-2 study [NCT02055781], patients were randomly assigned to pacritinib vs best available therapy, which could include ruxolitinib. In that setting, we can clearly see there is robust symptom response.2 In any patient with myelofibrosis, would we expect a similar degree of symptom benefits with pacritinib? It’s hard to say because we don’t have that overall direct comparison.

But when you’re thinking about patients with severe thrombocytopenia, when you’re thinking about patients in the second-line setting, can you at least hope to see some degree of symptom benefit when you would choose pacritinib in that setting? I think yes.

OGUNDIPE: It seems to be very safe…it’s quite a good drug. I have 2 patients on it, and they seem to be doing well. Ruxolitinib and fedratinib [Inrebic] [actually failed for 1 patient], and she was transfusion dependent and is doing great right now. The other patient I have on it has…secondary myelofibrosis from [essential thrombocythemia] and now has thrombocytopenia and she’s also responding very well to the drug. The [efficacy] data look very promising, and the safety data also look encouraging at this point in time.

OH: Can you tell us what your approach has been and what your experience has been regarding potential gastrointestinal adverse events? How did you counsel the patient? What was their experience, particularly initially?

OGUNDIPE: They both had mild diarrhea at the onset, but…it’s pretty well controlled at this point in time.

BADDI: Because it’s [given at] 200 mg twice a day, do you ever start them at 200 mg once a day? With some of the other drugs that [cause] diarrhea, we start them a little lower, then we go up to the full dose when the diarrhea settles. I [also] have a patient who has significant transfusion-dependent anemia. How long [does it take] to see the response regarding the anemia? If you don’t get something by 2 months, are you not going to get it?

OH: To your first question, my response is generally no. I would start at the standard dose of 200 mg twice daily. There was a dose-finding study, PAC203 [NCT03165734], that looked at lower doses, and there is activity at lower doses but it…appears to be less [From the Data4]. I would shoot for that 200-mg twice-daily dose to get the adequate response. My advice is to start with 200 mg twice daily, give them the antiemetics, remind them to have an antidiarrheal on hand, and I think it’ll go fine in most cases.

The second question was about timing of transfusion independence or anemia response. Based on the recent reanalysis we did, the timing of the anemia response was variable.5 It is conceivable that for some patients who may not have an overt anemia response right away, it could take several months. You want to be patient in that regard and consider that you’re probably not going to use pacritinib solely [because of] anemia. I would be using it for patients who have some degree of splenomegaly, some degree of symptoms, and are anemic. I’m looking for some compilation of those kinds of responses.

PODDAR: I work in the suburbs of St Louis, Missouri, and on the southern Illinois side, which is a rural area, most of my patients are older and have a lot of comorbidities. Given these safety data, how do you use pacritinib in someone who has cardiac issues, atrial fibrillation, and is on one of the newer oral anticoagulants? [How do you] explain to them the risk of bleeding?

OH: You raise important and challenging questions, particularly as you describe your practice setting. That raises it to another level in terms of the bar for safety in many ways. There was some concern about potential safety related to cardiac events and bleeding with pacritinib. It’s not surprising, to a certain extent, when you consider that this is a drug that’s been examined and is being used in patients with severe thrombocytopenia.

With that said, the reason for that dose-finding study that I alluded to was to more comprehensively examine the safety of the drug in that regard. When that was done and more careful attention was paid to cardiac issues and things like that, those safety signals did not come out.4 We must be more vigilant with these patients who have those very low platelet counts overall, but pacritinib specifically is not necessarily a huge factor as far as that’s concerned.

This is easy for me to say, and it may be not as practical for your practice setting, but I have increasingly worked closely with our colleagues in cardio-oncology who are particularly focused on patients with cancer and heart disease, and that’s been very helpful for our practice. I don’t know whether you have that necessarily readily available where you practice. Regardless, having close coordination with a cardiologist for patients with those comorbidities is helpful.


1. Vonjo. Prescribing information. CTI BioPharma Corp; 2022. Accessed October 2, 2023. https://tinyurl.com/yxjnn7yu

2. Mascarenhas J, Hoffman R, Talpaz M, et al. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis: a randomized clinical trial. JAMA Oncol. 2018;4(5):652-659. doi:10.1001/jamaoncol.2017.5818

3. Mesa RA, Vannucchi AM, Mead A, et al. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. Lancet Haematol. 2017;4(5):e225-e236. doi:10.1016/S2352-3026(17)30027-3

4. Gerds AT, Savona MR, Scott BL, et al. Determining the recommended dose of pacritinib: results from the PAC203 dose-finding trial in advanced myelofibrosis. Blood Adv. 2020;4(22):5825-5835. doi:10.1182/bloodadvances.2020003314

5. Oh S, Mesa R, Harrison C, et al. Retrospective analysis of anemia benefit of pacritinib from the PERSIST-2 trial. Clin Lymphoma Myeloma Leuk. 2022;22(suppl 2):S327. doi:10.1016/S2152-2650(22)01439-2

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