Reevaluating Available Options for Anemia in Myelofibrosis

Andrew Kuykendall, MD (Moderator)

Assistant Member, Department of Malignant Hematology

Moffitt Cancer Center

Tampa, FL

DISCUSSION QUESTIONS

• How do you monitor and manage anemia in patients with primary myelofibrosis prior to starting Janus kinase (JAK) inhibitor therapy?​
• While receiving a JAK inhibitor therapy?

Andrew Kuykendall, MD: How do you monitor and manage anemia in patients with myelofibrosis even prior to starting a JAK inhibitor? If you're initially evaluating someone, they come in with hemoglobin of 7 or 8 g/dL or something like that, how does that impact your thinking, and how do you work that up?

Lazaros Lekakis, MD: The first thing is to make sure that they don't have something easily fixable [such as] iron, B12, or folate deficiency. Theoretically, if you don't have any nutritional cause or any immune causes, you could use erythropoietin analogs, but they are very tricky because they don't help with the spleen, at least in my experience, and they may increase the risk of clots. I try to avoid them if possible. If I have to start a JAK inhibitor, if they have symptoms, either I go away from ruxolitinib [Jakafi] or I start a low dose of ruxolitinib. Sometimes I use anabolic steroids and prednisone. We have the thalidomide/prednisone [regimen] that now is kind of forgotten about.

Kuykendall: Erythropoietin-stimulating agents [ESAs] are limited in what they do, and certainly not helping other aspects of the disease. You did mention one of my favorite regimens, thalidomide/prednisone, which is looked over a bit nowadays, but has quite a potential for efficacy in terms of improving hemoglobin. But it’s probably something that's gone by the wayside in many practices.

Luis Sumoza, MD: As Dr Lekakis says, there are some other options that you can use. Danazol is sometimes something you can use perfectly in this patient population. From the JAK inhibitors, there is momelotinib [Ojjaara]. But a priority for me is to refer a patient for a stem cell transplant; when I was a fellow, we did the first allogeneic bone marrow transplant at the University of Illinois, Chicago, and it was a very nice experience.

Kuykendall: [Dr Lekakis] also mentioned steroids, [and we are] thinking about things like danazol, androgen derivatives. We saw from the MOMENTUM study [NCT04173494] looking at momelotinib that danazol is an active agent.¹ It was a large, randomized trial, one of the first randomized trials with danazol. The focus there was on momelotinib, but there's also a lot to learn about what danazol could do as well from that study.

Sumoza: You're mainly talking about anemia here, and [if], the patient is not a candidate for a transplant or a clinical trial [there are] the data about navitoclax/ruxolitinib, which basically double the response and reduction of the spleen.²

Kuykendall: Yes, these emerging therapies to some degree may change how we approach this disease. But I think that with some of these older therapies, especially when you're when you're first talking about someone who's coming in with anemia, you need to think about ESA, danazol, and thalidomide/prednisone.

I think that ESA is probably the most prominently used. How many of you are checking serum erythropoietin levels in these patients to assess their candidacy for ESAs, is that a common practice?

Mukesh Kumar, MD: Yes, I'm checking on all of my patients.

Kuykendall: Now in terms of the patient who develops anemia while receiving a JAK inhibitor, ruxolitinib or fedratinib [Inrebic], how do you then approach that patient? This is the someone on therapy who may not have had prominent anemia before, but now that anemia is a little bit more obvious.

Lekakis: I would reduce the dose. I cannot stop [ruxolitinib] easily because of the withdrawal symptoms, but I would reduce the dose.

Ashok Kumar, MD: I probably would be giving a lower dose or initiating at a lower dose if they are anemic, and then I can go up later if I have to.

Andrew Kuykendall, MD: With the option of reducing dose, and now newer JAK inhibitors that are available, how do you decide between changing therapy vs reducing the dose of ruxolitinib?

Ashok Kumar, MD: I would try to maximize the use of ruxolitinib and then go to the next drug.

Kuykendall: The most common answer in about half of the responders is that a hemoglobin of 7 to 8 g/dL is a concerning level. We’ve hit on this before that if ruxolitinib drops hemoglobin on average by 1 to 2 g/dL, if you start in the 7s, that means you're going to drop to the 6s at least, and that’s an uncomfortable spot to be. Others have said less than 7 g/dL, some 8 to 9 g/dL, and then at least one for hemoglobin levels not deterring from ruxolitinib initiation. But I think in general, the 7 to 8 g/dL makes sense from a pragmatic point of view, given what we know about ruxolitinib, and I've heard that answer quite frequently.

_{DISCLOSURE: Kuykendall previously disclosed consulting fees from CTI Biopharma, GSK, and Imago Biosciences; payment or honoraria from BMS, Incyte, and MorphoSys; travel support from AbbVie and MorphoSys; and advisory board participation with Incyte; no other relevant participant disclosures are known.}

_References:

_{1. Verstovsek S, Gerds AT, Vannucchi 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}

_{2. Pemmaraju N, Mead AJ, Somervaille T, et al. Transform-1: a randomized, double-blind, placebo-controlled, multicenter, international phase 3 study of navitoclax in combination with ruxolitinib versus ruxolitinib plus placebo in patients with untreated myelofibrosis. Blood. 2023;142(suppl 1):620.doi:10.1182/blood-2023-173509}