KISHTAGARI: The challenge as treating clinicians these days in the clinic is that almost 34% of the patients present with severe thrombocytopenia of less than 50 109/L platelets at the time of initial diagnosis of myelofibrosis. Most patients, 66%, presented with thrombocytopenia of over 50 109/L.1,2 This is a significant challenge when treating patients, especially with ruxolitinib [Jakafi], the medication that has had FDA approval for the longest time. The medication itself can cause [decreased] blood counts as well. A lot of patients do have anemia at baseline, and that gets worse with the disease evolution as well. So both thrombocytopenia and anemia are huge challenges for us. I think this is important in the sense that we need to monitor these patients frequently while they are on treatment. I think one [issue] is how frequently to monitor them. We should monitor them frequently initially, but once theyve stabilized, we can probably monitor them every 6 weeks to 2 months. Its been my practice to do 6 weeks to 2 months once they have
stability in their platelet counts, based on their treatment. Of course, if any drop in the platelet counts or hemoglobin happens, I tend to monitor them more frequently and include dose reduction of the treatment they are on.
ZAMAN: Recently I had a couple of patients who had hemolytic anemia, so they didnt take the prednisone. I gave rituximab [Rituxan] to a patient and she did not respond. I stopped it after 4 cycles with no response. Suddenly, 3 or 4 months later, she was not requiring as many transfusions. How often do you see hemolytic anemia?
KISHTAGARI: In my practice, I have seen 1 patient with hemolytic anemia with myelofibrosis. Its not that common, if you look at the literature as well. I keep thinking about management for this patient. Fortunately, my patient responded very well to high-dose steroids. But, like you said, its a challenge. That is something [that reminds us] when we see a drop in hemoglobin, we should always think broadly, not [only] of the disease but of the adverse effects [AEs] of the medication. We need to think broadly and keep our differentials broad. Look for hemolysis as a cause as well. But its rare, and it is reported in less than 5% [of patients], based on the literature.
BHANDARI: In my opinion, [the goals are] improvement of the symptoms and improved quality of life. The platelet count of 43 109/L is less concerning. I think the symptoms are more important.
KISHTAGARI: I think thats a good [approach]. A lot of these patients come with such a huge symptom burden, and I think thats the most important thing to address while we are thinking about the long term for this patient.
MAHAJAN: This is a 68-year-old patient. [Although] his ECOG performance status is 2, will a stem cell transplant [SCT] be a possibility for him? He is relatively young.
KISHTAGARI: Absolutely. I think a lot of times I give these patients the benefit of the doubt. I always refer for SCT, just for an evaluation. It doesnt mean that they will go for SCT. I think they need to at least be evaluated by a transplant physician to see if they can be considered for SCT. The oldest I have sent for transplant [was a 79-year-old patient], and this was a patient who was very active with an ECOG performance status of 0 to 1. This patients ECOG performance status of 2 is likely from the severe symptom burden he has been experiencing secondary to myelofibrosis. Given that, it is always good to initiate treatment and send them for transplant evaluation because we all know that the ultimate treatment or cure, especially for high-risk myelofibrosis, is SCT.
ZAMAN: If they are symptomatic, we start them on ruxolitinib. We look for the risk assessment, and Johns Hopkins [Sidney Kimmel Comprehensive Cancer Center] is approximately 100 miles from here, so I call them for an evaluation to see what they think. I try to cover both things, unless they are frail and cannot travel, which also is sometimes an issue.
MENDOZA: I have a similar approach. I sit down with them, and tell them that they need pharmacologic intervention, and we look at the performance status. We say that if they have some comorbid conditions, and they are highly symptomatic andhigh-risk, typically by guidelines, they would be candidates for transplant. But if the performance status is 2 and we start treatment and that improves their symptoms, then thats when I say we are 50 miles away from [a transplant center in] Baltimore, Maryland. So we also do something different, and typically the response is quick. Now in this case, discussing the specific pharmacologic agent is a little bit tough because of the platelet count. I would be careful with the choice. I would probably phone the transplant [specialist], go over the case, and say this is what I want to do. I want to see if they improve on pacritinib [Vonjo] or some other type of agent, and if it is indicated, Ill start that, and 2 to 4 weeks later I will see them and they have improved. The patients can tell when the spleen gets smaller. That by itself improves their symptom burden, and if thats the case, then the next thing we do is send them to Baltimore [for transplant evaluation].
KISHTAGARI: Thats fantastic. I like that approach a lot.
KALRA: Most of us who are in the community dont have open trials for patients with myelofibrosis, but at least I am in Baltimore and have access to 2 large academic centers, and if this is a patient who would qualify for a trial, and its open at one of those centers, then [I would refer for clinical trials].
LANG: If a patient has high-risk myelofibrosis but does not have clinical symptoms and is a candidate for transplant, do they still benefit from bridging therapy with a JAK [Janus kinase] inhibitor?
KISHTAGARI: If they have splenomegaly, I would consider JAK inhibitor therapy prior to proceeding to allogeneic SCT because if you can control the spleen size as much as possible before going for transplant, [data from] multiple studies have shown that it has a good outcome post transplant.3,4 So at least for the spleen reduction, I recommend initiating a JAK inhibitor.
ISLAS-OHLMAYER: Would you continue the JAK inhibitor during SCT?
KISHTAGARI: That is something a lot of centers have been doing. We have also been doing it after SCT, not during SCT. After SCT we have been initiating JAK inhibitor therapy because the symptom burden sometimes comes back, and we continue them on ruxolitinib. [N]ot all of them, [however,] only a few patients. This is being done as a part of a clinical trial, not as a standard of care.
KISHTAGARI: Getting a donor is something we all face whenever we refer the patient for allogeneic SCT evaluation. I have a lot of patients in my clinic right now who do not have a donor, and thats a significant challenge. Access is also something we all face for transplant evaluation, and even the cost is something we dont talk about often, which we should. They need to be very close to the transplant center, at least for the 90 to 100 days when they are undergoing allogeneic SCT evaluation. Do you always refer for transplant if they have high-risk myelofibrosis?
MAITI: Yes, the high-risk patients. I am at a regional oncology center close to the Cleveland Clinic main campus [in Ohio], so if I see a patient with high-risk myelofibrosis, I would refer them to a [transplant physician] on the main campus and work on the bridging therapy.
KISHTAGARI: OK, good.
MISBAH: Usually [the transplant physician] will tell us the bridging therapy they want us to use.
KISHTAGARI: Do they have any preference for the bridging therapy that they recommend?
MISBAH: I havent referred anyone recently, so I wouldnt be able to speak to that. But usually they will guide us very well on what we should use or what their preference is.
KISHTAGARI: Do you have any experience? [For] how long do you use bridging therapy? I know that very few patients subsequently undergo transplant.
LANG: In the past couple of years, I referred 3 patients for transplant. I was thinking they continue the bridging therapy until you find a transplant donor.
KISHTAGARI: So until the transplant donor is identified, and then until they go to transplant, the bridging therapy is continued.
LANG: Right.
KALRA: I think its the patient population. Myelofibrosis is not a disease of young people. Its the comorbidities. Its obviously the availability of donors. Its a lot of those factors, and then, eventually, whether they can even tolerate a transplant.
KISHTAGARI: Good. I think those are the challenges we face as clinicians on getting these patients [to transplant] with their advanced age, as well as donor availability and their performance status. Other factors such as cost and access are at play. Lately we have been seeing debulking of the disease before going for transplant. I think thats less of a challenge compared with other diseases such as AML [acute myeloid leukemia] or MDS [myelodysplastic syndrome] where they prefer the [myeloablative conditioning] before going for SCT. I dont think we have that challenge here. We have other challenges with myelofibrosis.
BHANDARI: I think its promising. I have used it in 1 of my patients.
MAITI: I have not used pacritinib yet. I have only used ruxolitinib as first-line therapy. But with the data,5 I think especially in patients with a platelet count of less than 50 109/L, I would consider pacritinib.
KISHTAGARI: In patients with a platelet count greater than 50 109/L, also, one can consider pacritinib, especially in the second-line setting.
KNAPP: Patients had platelet counts of less than 100 109/L on the trial, but they only approved it for those with less than 50 109/L. Is there a reason for that?
KISHTAGARI: In the [PERSIST-2] clinical trial [NCT02055781], they looked at both groups, but patients with platelet counts below 50 109/L derived maximal benefit [From the Data5], and so the FDA only approved it for that.6
MENDOZA: If I have a patient who is on dose-adjusted ruxolitinib, hes borderline, he had initial counts greater than 50 109/L, but he developed a platelet count of less than 50 109/L, do you recommend switching to pacritinib at that point? Or would you rather hold the dose, wait, and then adjust ruxolitinib again?
KISHTAGARI: It all depends. If the patient is getting benefit from ruxolitinib and you only noticed significant thrombocytopenia, dose reduce first before switching to pacritinib. If with the dose reductions you do not see any improvement in blood counts, then definitely switch to pacritinib.
MAHAJAN: What about pacritinibs effect on anemia? Is it like ruxolitinib, or other than that do you have to wait for momelotinib [GS-0387] to be approved?
KISHTAGARI: What we have seen is pacritinib also inhibits a protein called ACVR1 more than momelotinib.7 We also see this in the clinic as well, where there is a significant improvement in hemoglobin. But you need to treat the patient longer, and there are some retrospective data where they are noticing an improvement in hemoglobin along with a stabilizing platelet count.8 So there might be a role for pacritinib in the future for patients with myelofibrosis and anemia.
Excerpt from:
Roundtable Discussion: Kishtagari Reviews Treatment and ... - Targeted Oncology
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