Immune Thrombocytopenia — Microlearning Activity 4 with Dr Hanny Al-Samkari: ASH 2025 Review

Welcome to What Happened at Ash, the American Society of Hematology meetings in December 2025. Immune thrombocytopenia are we entering a new age of treatment of this entity, specifically the use of BTK inhibitors and BAFR antagonists, B cell activating factor receptor antagonists. This is a medical oncologist, Dr. Neil Love.

I met with doctor Hanni Alsum Carey from the Massachusetts General Hospital in Boston, Well in this final issue of our four part series, doctor Al Samkari again responds to a series of cases presented by community based oncologists. doctors Tina Botnager from Wheeling, West Virginia, Susmita Apori from Ivernus and Lakanto, Florida, and Sunil Gandhi also from Lakanto, Florida.

The first case was presented by doctor Botniger. He was initially managed with pulse dexamethasone at a dose of 40 milligrams daily and then received two IVIG infusions, but his platelet counts didn't really respond. He's a young guy, he has a three year old at home and was wanting to get discharged as soon as possible. So in the hospital we kind of You know. bombarded him with additional ITP directed therapies consisting of Rhymplostem.

And he also received four days of pulse dexamethasone and then we restarted prednisone at a dose of one milligram per kilogram. And he also initiated Rituximav. while he was an inpatient and subsequently his counts did improve, going from four thousand to eventually a hundred and eighty seven thousand by the end of the month. He finished four weekly treatments of Rituximab. We were able to taper him off prednisone and he's currently not on anything for ITP.

He did, however, have some persistent anemia and amidst that workup was found to have a TSH of 124 and an undetectable free T4. He started levothyroxin and his anemia improved and is now near normal at 12.8 grams per deciliter. So my question to the experts is what their threshold is for doing platelet transfusions. Would also love to know thoughts on how this could have been managed differently or alternatively. And I'm assuming that the ITP may have been related to his

thyroid disease, which is probably also autoimmune. But if there are any other additional long term considerations that they would take into account when monitoring this patient for relapse, he's doing very well currently. So who likes ITP h hostages in the hospital, right? Everybody wants to get the patient out of the hospital. The patient wants to get out of the hospital. This is a young guy, three year old at home, you know, he's got a life. You got to get back to that life.

Um and so it's perfectly reasonable if someone is, you know sort of stuck in the hospital not responding to typical first line therapies. Yeah, to throw on rimplostem. I do it all the time. You know, trying to get a patient out of the hospital as quickly as possible. The one thing you gotta look out for, right, if you give a patient DEX and you give them IVIG and you give them, you know, a high dose of rimplostem, right, you might get some thrombocytosis.

Right, so you just have to be a little bit, you know, weary of that possibility. Chances that they have any issue related to that are are low, but it's uh it's always something to just think about. Um but yeah, I I would say that um it's okay to uh particularly in people that don't respond to corticosteroids and I VIG. in that early early phase and the first few days to add on a T PRA or MIPLASTIM five milligram or microgram per kilogram, you know. Um

Uh this guy also uh uh ultimately finished Rituximab um and has uh uh currently been off of ITP therapy for some time, hopefully for a long time. We'll see. what ends up happening if he relapses, I would not give him Rituximab. I would give him uh uh you know, either a thromopoint receptor agonist uh for long term use or something like real zebrut nib or uh uh uh phosphanatnib. Um and uh let's see, what's the thr the other question here is what's the threshold for doing platelet transfusion?

I only use platelet transfusions in people who are actively bleeding, um, with significant internal bleeding. Um and it and it's it's it's not an easy thing because one of the things we know about giving platelet transfusion is you're giving a big bolus of colloid. And when you do that, if someone has a brain bleed and that brain bleed is not being intervened on, you can increase the pressure in those ruptured vessels in the head, and that can make the bleed worse.

Right, you can increase hydrostatic pressure by giving big boluses a colloid. So when I do it, I give the platelets very slowly. And I will give I V I G to try to actually allow the the person to respond to the platelet transfusion, um to have a higher likelihood of response. And I won't go nut I'm not gonna give them two, three, four, five units trying to hit an arbitrary goal of fifty thousand or, you know, seventy thousand or whatever.

uh that sometimes we we you know uh uh try to try to achieve or sometimes proceduralists want us to achieve, right? I'm I'm I'm using it primarily to achieve hemostasis. I want to see things stopping a a and and the bleeding getting better. And I would also write reach for tranexamic acid or amino caproic acid infusion as an S fibre analytic. Uh a at the same time or before I reach for a platelet transfusion to try to get that bleeding to stop.

Any thoughts about her thought that this ITP might be tied into the thyroid uh issue? Uh and and what do you see with people uh do there You know, you hear about their thyroids quote burning out, but has the autoimmune process stopped? Is the ITP usually temporary or can you see relapses?

It's a great question. It's extremely common to see ITP a concurrent or uh a following autoimmune thyroid disease. Totally. Very, very common. Uh patients with ITP very commonly have anti-thyroid peroxidase antibodies. Um even if they don't have thyroid disease. Um the natural history of the two diseases tends to be separate.

So even if someone's thyroid disease is getting better or burning out, their ITP might be ramping up. Um tip typically they don't tend to run together. Um obviously every patient is different, but they typically don't tend to run together.

So doctor Apori has a really interesting case, I'm curious what you think. Eighty one year old Caucasian woman, she has underlying COPD and she did present with progressive shortness of breath that led to a CT scan, which showed a left sided prolifusion. She underwent a thorough synthesis and the pleural fluid was consistent with metastatic adenocarstum of the left lung. And this was almost three years ago. She came to me in a wheelchair, I still remember, asking if she should go to hospice.

So she was initiated on carboplatin, permitrexide, and permalismab. She did relatively well despite her COPD and she was started on maintenance immunotherapy. And while she was undergoing immunotherapy, she presented with an acute thrombocytopenia and very mild anemia and the platelet count was twenty one thousand. And her platelet count was consistently above one hundred and fifty thousand all along while she was on immunotherapy.

I did treat her with steroids. There was a very brief response. The platelets went up to forty thousand. But as soon as I taped up the steroids, they would come back to under ten thousand. So during this time the immunotherapy was held, the bone marrow biopsy did show a normal cellar marrow with trial inage hematopoiesis and the megacaryocytes are preserved. And there was really no evidence of hemolysis or PNH in the purple blood.

So I did initiate her on L thrombopag, I think only out of the thought process that I want her to complete her maintenance immunotherapy. She did very well on the L thrombopag and I changed the treatment to three times a week. Her platelets were consistently above fifty K and she completed the immunotherapy. And I discontinued the L thrombopack because I said, Let's see, you know, what happens. She's done very well and she's not really symptomatic with uh thrombocytopenia anymore.

So she's been off the L thrombopag now for over six months and her platelets were consistently above hundred K. So my question to the experts with how often do you see Immunotherapy induced thrombocytopenia. This is my first case and I have given my fair share of immunotherapy to our patients. How would you treat this patient?

Would you leave them on the L thrombopag and taper it down slowly? Because her current platelet count after six months is now trending in the eighties and nineties. So there has been a drop over time. but really not a significant enough drop for me to re-initiate any therapy. And in these individuals who develop the thrombocytopenia, how often do you see a recurrence?

So whenever you see uh an immune checkpoint inhibitor related uh hematologic complication like ITP or auto-immunity hemolytic anemia, my number one goal, in addition to obviously managing the acute cytopenia issue.

is getting that patient back on their IO, especially if they're responding really well to the immune checkpoint blockade. Um in this case, right, the patient responded beautifully to it and and you wanna be able to continue it. And so You know, uh immune checkpoint inhibitor induced ITP happens in about one in four hundred patients, as was very nicely shown by my colleague, Dr. Karp Leaf's uh abstract. uh uh of ICI ITP

uh presented at Ash that really showed I mean this was a big study of a lot of patients from many large cancer centers. You need a very large population in order to have enough patients to really analyze. Um and it showed that, you know, most patients recover.

And you can use steroids, you can use IVIG, you can use TORAs, the response rates are relatively similar. Most patients recover and it when you rechallenge, most patients don't relapse with the ICI ITP. When you rechallenge with the immune checkpoint blockade. So I that's uh you know, uh uh always my goal. I mean Right. You can have really bad ITP. I I I've had patients that have had ICI ITP that's been more challenging to treat, but I've never had a circumstance.

or haven't been able to get them back on their immune checkpoint blockade and maintain a reasonable platelet count. Sometimes, right, the cytotoxic chemotherapy may have to go by the wayside or it may need to be dose reduced or what have you. uh if their ICIITP is particularly challenging to treat. But but for the uh immunotherapy, we generally are able to get that back on board and keep it on board. Um and this this study again showed that

We c we can be quite successful in managing it. It does, however, portend an overall worse diagnosis for the patient, right? this study showed that that patients that had more severe ICI ITP had more mortality after controlling for all of the oncologic you know, uh uh related issues, the tumor type, the stage, you know, uh all the relevant things. So, you know, we don't want to see it happen, but when we see it happen, we can manage.

So let's hear what you think about this case from doctor Gandhi. 78, he was diagnosed 30 years ago. When he presented with large bruise on the face, platelet count was one thousand, classical ITP. He moved to our town in twenty twenty one. I gave him retoximab and prednisone but his ITP was minimally responsive to that regimen. So in August twenty twenty three I put him on ever trombar.

He responded he is in complete remission. His platelet count went up to even two hundred thousand, two fifty thousand. So I'm gradually reducing the dose. It is twenty milligram four days a week and I'm trying to make it much less. Because this is one drug the studies are you can give on once a week. So my goal is if I can go to once a week and maintain it.

But I'm using Avatrombopack quite often. Question is, am I using the right drug or I should be using another drug? One another thing is Say you are in a hospital round, you see pay another patient with one thousand platelet ITP and you want to start should we go with high dose steroid like pretnisone one to two milligram per kg or dexamethazone forty milligram for four days?

And another question is in newly diagnosed ITP, when we usually start with steroid, should you put retoximab in all of them or most of them? So the first question, uh you know, you definitely are using the right drug, right? This patient has challenging ITP and has responded beautifully to Avatromba peg. And you're lowering the overall drug exposure. With Avatraumapag, uh, it's uh done by reducing the number of pills the person takes per week. This is only one pill strength, unlike L trauma peg.

Which you can get seventy five, fifty, twenty-five, twelve point five. Avatron bags is twenty milligram pills. And so you go from seven days a week to five days a week to four days a week. You can go all the way down to one day a week. Um, and some patients they need that whiff of avitrombipag. They need that just a little bit. in order to prevent them from crashing. So you definitely are using the right drug. Um and uh I think that it is um appropriate to continue to

try to slowly wean him down. Um and if if he maintains a platelet count above a hundred thousand, you could try to wean him off and see if he has a s sustained response off treatment. Um but if you're getting, you know, into that thirty to fifty thousand range after lowering his dose, then I would probably just stick to whatever dose you're at uh when he gets to that thirty to fifty thousand range.

What about his question there about rituximab and whether when you incl include it with uh corticosteroids in a uh upfront? I don't use a lot of Rituximab on front with corticosteroids. I will say that it is uh uh uh coming in the updated ash guidelines for ITP that you can consider doing that. Um combination therapy. My main concern with Protuximab is that I know it's not disease modifying, and I know that.

There's some nice data that has been published and people with ITP spleens after they get Rituximabin com compared to patients who've not gotten rituximabin it it may actually make the autoimmune response more recalcitrant. So I try not to do it. I I actually really primarily reach for Rituximab more in the salvage setting myself.

Right, it is off-label for ITP. It's perfectly reasonable to use and the guidelines recommended as a as a uh uh a therapeutic option. Um and there's good data uh to suggest, you know, to support its clinical use. Um but at the same time I'm you're not I'm not curing anybody with this drug and I may be making things a little bit more challenging in terms of down the road. So I try not to reach for it and I uh uh uh uh except in kind of a lever line setting.

So uh final question about this case. Looking back to when this patient was started on avid trombopag. When you think about that situation, uh if you had uh Ltrombopag plus uh Yanilomab available, would you have used that? Yeah. Uh this is a circumstance where it's somebody who had already gotten Rituximab, so a little bit different than the Vay hit two kind of situation, but I I think that um even though it's not exactly the same, I I would have offered it uh to the patient, right?

Uh and it wouldn't necessarily have to be with Eltromapag either, right? Uh uh the data is with El Trombag, but once we have a UNALAMA. in clinical practice, I would not hesitate to combine it with other TPRAs because they function similarly as a short course of TP RA uh getting you to the point where you can be off of all therapy after giving the analomab with it.

Um but yeah, I think that that's that's something I would offer to this patient too, um, uh particularly given that he has very chronic disease. You know, he's he's been um uh uh uh he's had ITB for a very, very long period of time and he might benefit from a very potent combination type approach.

That's really I never thought to ask you this'cause I assumed you would say no, but are so you're saying if you had Yanala Mab available, you might combine it with another TPO other than Eltromopack? Uh yeah, I would. Um I L Ltrombapeg is a perfectly reasonable drug to use and obviously the clinical trials used it, but uh you know, Ltrombeg, right, has dietary restrictions associated with it. You can't

You basically need to be fasted for four to six hours around taking it in order for it to absorb properly. Um it causes hepatotoxicity in about ten percent of people who take it. Um in high doses it can cause some muddying of the sclera and the skin where people have almost like a darkening of their eyes and and if they're fair complexion their skin and that that can be undesirable for some patients.

Um and uh so there all of these things are things that Avatrauma paga riplostem don't have, right? So um I I I in in practice these days the oral TPR TPORA that most patients prefer to use a Zava trauma peg because it's easier to uh to take and you don't have to monitor LFTs for a year and you don't have to worry about the dietary stuff.

That's really great. We just got back from the San Antonio Breast Cancer Symposium. You know, they're they're very, you know, I don't know, Talmudic according to the book. If the you know, there's these a lot of trials now with C D K inhibitors and uh SERDs. But you know, there's one study that has a specific C D Kemacyclib, a specific CERD immunesterin. And that's all people and it's uh w will use. It's very interesting that you kinda have a different uh

approach to it really uh makes a lot of sense though. It's this the tolerability and the m mode of administration that makes Uh the difference for some of the things that we're going to So let's hear about this uh final case from doctor Botniger.

I have an 82-year-old woman who actually has numerous medical comorbidities, including heart failure, COPD, type two diabetes, hypertension, hyperlipidemia. COPD and stage four CKD. She has a longstanding history of moderate ITP with platelet counts ranging between 40 to 50 K. She had been following with a separate oncologist who was managing her. Basically with steroids during acute exacerbations, but really no other interventions.

I met her as an inpatient when she was there for confusion and fluid overload as a result of a CHF exacerbation, and at that time her platelet count was 19,000. Historically, she's had immense difficulty tolerating steroids as a result of their toxicity. I was concerned of the risk of exacerbation of cardiac comorbidities with L-Trombopag, so I started her on Fostamatin, 100 milligrams twice a day. And within two weeks, her platelet counts improved.

from nine thousand to a hundred and fourteen thousand. And for the rest of her treatment course she stayed between eighty to a hundred thousand, really with no significant toxicities. So my question is whether the experts can comment on the advantages of FOSTMATNIB and in which clinical situations they generally use it and are there any special treatment considerations when choosing this drug.

Did she ever get uh I VIG or rituxima? She never did. I thought it might just be easier from a logistical standpoint for her to take a pill rather than come in for infusions. So this is a great example of how phosphomatinib as a spleen tyrosine kinase inhibitor can be very useful in some patients with ITP. This patient responded beautifully, relatively quickly.

Um uh uh recognize that right with Fosna Matinib started 100 milligrams twice a day, but you definitely want to up titrate to 150 milligrams twice a day if you don't have an adequate response at the end of one month. Sometimes right you can g you can uh uh sort of Uh quit prematurely, so it's important not to do that. Try the the higher dose if they don't respond to the lower dose. This patient didn't need a higher dose, they responded very nicely to the lower dose.

And got a platelet's really a goal and really consistently there. This is exactly what we want when we start a patient on FOSTMADNIB. And so the question is. You know, what are the advantages of phosphomatinid? Fosto matinid it has no theoretical thromboembolic risk, like uh T Boras have a theoretical thromboembolic risk. And in this case, right, the the concerns

about the patient's cardiac status uh uh were center stage and that led to avoiding a drug like Ltromapag, avoiding a TPR A because of that risk. Um uh fosta matinib is uh may actually be anti thrombotic. It actually may reduce the risk of thromboembolism as b has been suggested in some uh basic science studies.

Um the uh uh patients who respond to phosphomatib tend to be very stable on on their on their drug and and can continue for very long periods of time with little challenge, uh and that's great. Fosnomatib is associated with a fair burden of side effects in some patients. Not in this patient, thankfully. Um, but uh it causes a decent amount of hypertension. You know, about uh a quarter to a third of patients will get hypertension.

Sometimes that hypertension is pretty significant and requires multiple anti hypertensives to treat. Um patients it's tyrosine kinase inhibitor. Patients get diarrhea, they can get rash, sort of other TKI type uh adverse events. Um but when it works well and the patients don't have uh uh concerning side effects, it can be exactly what you need. And and that was a really good example in this case. What about Rilza Brutnib in a patient like this?

I think Rosa Brunett would have been a great option in a patient like this. uh uh for similar reasons, right? Being able to potentially avoid a T Pore A in an older patient with a lot of cardiac disease. Um Rosa Brutina when people respond, they tend to respond with

um uh pretty good stable platelet counts. And overall, right, the side effect burden of rules of brutnib I would say is is less than phostimatnib. Obviously it didn't matter for this patient. They responded great to phosphatnib without side effects. But I would have uh certainly considered Rulza here as well. What about Yanalomab, single agent? Yeah, if Unalimab was available, then I think that would also be another consideration here.

Um this is somebody who uh if they're on um chronic antiplatelet or anticoagulant therapy uh as related to their cardiac disease and there's a lot of concern about you know, definitely wanting to uh of uh avoid the potential for the treatment effect wearing off of an episodic treatment, I might be more likely to reach for RILSA or FOSTA than Yanalimab in someone like this, but Certainly an option. That's kind of cool.

program. Special thanks to Dr. Elsom Carrie and thank you for listening. This is Dr. Neil Love for What Happened at Ash 2025, ITP.