Considering Therapy in a Patient With Myelofibrosis Eligible for Transplant
During a live event, Mark J. Fesler, MD, and participants discuss next steps for a 68-year-old patient with intermediate-risk myelofibrosis.
Mark J. Fesler, MD
Hematologic Malignancy Specialist
Director of Bispecific Immunotherapy
St. Luke’s Center for Cancer Care
Chesterfield, MO
CASE SUMMARY
- A 68-year-old woman presented to her physician with symptoms of mild fatigue.
- Spleen was palpable 6 to 7 cm below the left costal margin
- Past medical history: no known comorbidities
- Next-generation sequencing testing: JAK2 V617F mutation
- Karyotype: 46,XX
- Bone marrow biopsy: megakaryocyte proliferation and atypia with evidence of reticulin fibrosis
- Blood smear: leukoerythroblastosis
- Diagnosis: primary myelofibrosis
- Risk
- Dynamic International Prognostic Scoring System: intermediate-1
- Mutation-Enhanced International Prognostic Scoring System for Transplantation-Age Patients: intermediate risk
- Laboratory values
- Red blood cells: 3.40 x 1012/L
- Hemoglobin: 9.7 g/dL
- Hematocrit: 32.3%
- Mean corpuscular volume: 94 fL
- White blood cells: 23.0 x 109/L
- Platelets: 450 x 109/L
- Peripheral blood blasts: <1%
DISCUSSION QUESTIONS
- In your experience with myelofibrosis, which symptoms/presentations have the most negative impact on patients’ quality of life?
- In your practice:
- What is the trigger to initiate therapy for a patient with myelofibrosis?
- How important is it to initiate therapy early?
Mark J. Fesler, MD: In your experience with patients with myelofibrosis, which symptoms or presentations tend to have the most negative impact on a patient's quality of life?
Nicole Jacobi, MD: I think fatigue is a big issue, and the other one is early satiety, looking at the patient’s spleen and consecutive weight loss from that.
Fesler: This patient has fatigue, maybe in part related to the moderate anemia. We're not told that they have symptoms of splenomegaly, but the patient has an enlarged spleen objectively. Sometimes it's about asking these patients about symptoms and eliciting the symptom score.
What's your trigger for somebody like this patient with myelofibrosis potentially to initiate therapy? Do you always start with the JAK [Janus kinase] inhibitor? Do you use other types of medicines in this situation?
Pallavi Jasti, MD: Typically, anybody who falls into intermediate risk or higher is going to start thinking about treatment, especially those who are symptomatic from the disease. The cytopenias or splenomegaly with constitutional symptoms are all the things I look at before initiating treatment. Most often, people go on JAK inhibitors. In rare cases where the patient has only significant proliferative component with no significant cytopenias, I may consider hydroxyurea, but that's very [uncommon].
Fesler: Thanks, Dr Jasti. For this patient with intermediate-2 [risk], it sounds like this would be a patient whom you would probably launch into a treatment right off the bat, based on the fatigue with anemia. Does someone else want to chime in about [when] we initiate a JAK inhibitor for a patient like this? What agent specifically would you be thinking of for a patient with this disease profile?
Priya Kumar, MD: For this patient with anemia and fatigue primarily, I would consider momelotinib [Ojjaara] for the treatment of fatigue, and the anemia is a predominant cytopenia, so that's why I would pick momelotinib.
Fesler: So Dr Kumar says momelotinib, maybe for erythropoiesis-stimulating properties, maybe for some concern about initially worsening the anemia off the bat. Does anyone else want to chime in on choice of JAK inhibitor?
Melhem Jabbour, MD: I always collaborate with the transplant team. Does any drug between ruxolitinib [Jakafi], pacritinib [Vonjo], or momelotinib, affect the transplant down the road? Is there anything we should not do before transplant, or [is there a preferred] bridging? Or can I do whatever I want depending on the platelet count or the anemia?
Fesler: Dr Jabbour, I think that's a great point. This 68-year-old patient is somebody whose risk profile disease is potentially high enough that they should be considered for allogeneic transplant. It sounds like you might consider an early referral to a transplant center, depending on the circumstances. We are told this patient doesn't have comorbidities. It does seem like this is potentially a patient that might be considered for transplant. I was a transplanter at one point in my career. I don't know of any literature that would suggest that [any] JAK inhibitor would be potentially frowned upon from a transplant perspective. I think all these patients would potentially see JAK inhibition before allogeneic transplant. These are types of transplants that require sometimes months to organize and finding a donor. [Dr. Chhabra, as a transplant physician], do you have thoughts on how a potential allogeneic transplant might influence therapeutic decision making for you?
Saurabh Chhabra, MD: I agree with you. I don't think there are any data suggesting that we should use only one particular JAK inhibitor. Most of the experience that we have is with ruxolitinib, but we're seeing more and more experience with pacritinib now. At the end of the day, we want to control the symptoms, reduce the spleen size, and buy more time so that we have a donor available and have the comorbidities managed properly, and have some sort of response to the treatment. I don't care what treatment was chosen for the patient, whether it's momelotinib, fedratinib, or pacritinib.
Fesler: Very good. We're talking about initiating therapy on this patient, potentially referring for allogeneic transplant. I think our choice of JAK inhibitor is probably one of the most interesting points of discussion. We're talking about having this patient hopefully respond to the JAK inhibitor before they undergo transplant and potentially improve some of the symptoms. [We may] improve anemia but certainly are improving the spleen size. There are some data that having a larger spleen going into transplant might be an adverse prognostic factor, so that's something we're going to want to follow with serial assessments.1
Jacobi: One of the things that I've experienced, and that's maybe more in the remote past, is transplant is usually being done quite late in the game. The outcome from allogenic transplant in this setting is not as good compared with acute myeloid leukemia, because there are engraftment issues. I tend to send out patients relatively early, when they're young, but I feel like the medication route needs to be walked down to the very end.… The transplant is being done at a much later point.
Fesler: I think that's right, Dr Jacobi. It seems like most are saying that they would start the JAK inhibitor right now, try to get an optimal response, reduce spleen size as much as possible while that donor acquisition has taken place, and then potentially transplant at the point of maximal response. But whether a patient should see 1, 2, or 3 JAK inhibitors before allogeneic transplants is going to depend partly on [how] high risk their disease profile is, how that plays out and changes over time, and what their transplant risk is. This person at the age of 68 would have to enter a transplant cautiously, but they're at a transplantable age.
How about clinical trials? What role would clinical trials play for a patient like this?
Karim Anwar, MD: I think if a clinical trial is available, he should participate in it. Back to the choice of the JAK2 inhibitors, apart from this spleen size reduction, have they shown improvement in survival over hydroxyurea?
Fesler: To answer briefly, ruxolitinib in the COMFORT-1 and COMFORT-2 studies showed an overall survival advantage.2 We don't know if that's the case in terms of improvement of overall survival with the other JAK inhibitors. I think that that remains to be seen for the other 3.
DISCLOSURES: There were no known relevant disclosures by the participants.
