During a Targeted Oncology™ Case-Based Roundtable™ event, Jonathan Abbas, MD, discussed with his fellow clinicians the use of allogeneic hematopoietic stem cell transplant in patients with myeloproliferative neoplasms and how ruxolitinib fits into their care.
A 68-year-old woman presented to her physician with symptoms of mild fatigue, moderate night sweats and abdominal pain/fullness lasting 4 months; she also reported increased bruising and unexplained weight loss. Her spleen was palpable 8 cm below the left costal margin. Genetic testing showed she was negative for a JAK2 V617F or CALR mutation. Her karyotype was 46XX and a bone marrow biopsy showed megakaryocyte proliferation and atypia with evidence of reticulin fibrosis.
A blood smear revealed leukoerythroblastosis and she was diagnosed with primary myelofibrosis with a DIPSS (Dynamic International Prognostic Scoring System) risk score of intermediate-2 and also had an intermediate MIPSS70 risk score.
In your practice:
JONATHAN ABBAS, MD: Is this a patient where from day 1 you’re talking about an allogeneic [hematopoietic stem cell] transplant [HSCT] referral? Is this a patient that a transplanter would want to see early in the disease course or is this something that you might want to hold off on a HSCT consult until something isn't behaving as well as it could?
JEREMY PANTIN, MD: The [patient is] approaching the age limit where things are going to start getting [difficult] and not somebody that we'll take straight to allogeneic HSCT transplant, but you probably want to consider therapy to reduce that spleen size. If the patient appears to not have comorbidities and may be a good candidate for HSCT, the intermediate-2 or greater risk will certainly allow them to move forward, in terms of the favorable risk-to-benefit ration, if everything is aligned.
MICHAEL T. BYRNE, MD: I think we used to argue about this, not argue [necessarily], but these were the hard patients because nobody knows what to do with them. She's the right age for transplant, but also, transplant is not without risk. Quality of life is probably worse after an allogeneic HSCT than it could be without, so I don't know. I think you plug her in then you see what her donor search looks like, and regardless of whether she goes to treatment, I think this is somebody that you probably treat if for no other reason than to try and improve her quality of life.
OLALEKAN O. OLUWOLE, MBBS, MD: I completely agree with what my colleague just said. We have several targeted therapies in this area, and we can just find 1 to give them to control their symptoms.1 If that fails, there will be another. There are many in development, so for those who are not keen on getting transplanted, there is a viable pathway to just keep treating them. Now for the patient who says, “I want to see what the odds are,” like what [Dr. Bryne] said, find out if they have a donor, talk about the risk-benefit, and go for it.
ABBAS: From my HSCT days, I would totally agree with you. I think this is a patient I would want to see early, to explain that you might not need me now, but you might need me one day. You've potentially got years left of transplant eligibility, and we don’t have a crystal ball about how your response to treatment is going to be and where this disease is going.
Then just to be the devil's advocate for the case, this is a lucky one where we had intermediate risk with 1% blasts. If this [patient] had 6% or 7% of 8% blasts and we were now nudging closer to high risk, that might sway all of us to maybe think initially therapy might be more of a bridge to HSCT, because there might be a little bit less stable disease.
[This] is a symptomatic patient. Is there anybody out there who would watch and wait with this patient regardless of whether they are seeing the allogeneic HSCT team or not? Or does everyone feel this patient warrants some therapy?
RYAN CARR, MD: Yes, based on her symptoms, if you tried to watch and wait, so [the patient] might end up seeing somebody else.
ABBAS: I agree with you. She will certainly be finding another group in town if you said, “You have [myelofibrosis], but it's not that big a deal. Let's just see you back in 3 months.” I think it's unanimous this is a [patient] who's not a watch-and-wait case. They are out there, but this is not her.
Additional lab values showed the following counts:
ABBAS: [If there is] thrombocytopenia at baseline, I guess we have 2 options for this. One would be; are we comfortable still sticking with ruxolitinib [Jakafi], which we all agree on [in a patient case like this], but dose modifying potentially for thrombocytopenia or would just any thrombocytopenia necessarily make us think about another agent, if anybody wants to weigh in on it?
BRYNE: I think a thrombocytopenia of 140 × 109/L is different than thrombocytopenia of 30 × 109/L. That's quite a difference [between the level where a patient should receive] ruxolitinib vs pacritinib [Vonjo].
ABBAS: Yes, I would agree with you. Without the specific measurements, it's hard to say. Just also remember you certainly can, and we've been doing for years is dose decreasing the ruxolitinib with a lot of benefit.2 Unless you're in that extreme situation like down below 50 × 109/L platelet count, I still think there's a window to go with the tried and true [method here].
How about frailty? How about if this woman, let's say she was extremely frail and it wasn't necessarily a disease-related frailty, just other comorbidities? Would that sway us? Do we feel that JAK inhibitors are particularly tough on patients? Would this factor in at all if she were 78 years old or if she was 88 years old?
JACK ERTER, MD: No. I think this drug is, all things considered, quite on target and easy to take for most patients. I would certainly have no hesitation to give an 88-year-old a trial at a dose-modified start of ruxolitinib.
1. Li B, Rampal RK, Xiao Z. Targeted therapies for myeloproliferative neoplasms. Biomark Res. 2019 Jul 16;7:15. doi: 10.1186/s40364-019-0166-y
2. Mesa RA, Cortes J. Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing. J Hematol Oncol. 2013 Oct 22;6:79. doi: 10.1186/1756-8722-6-79