DR SMITH: The 56-year-old who presented with low- to intermediate-risk disease from the standpoint of a Sokal score. White count was not markedly up, 47,000. Platelets were slightly up at 510,000. And he did have a spleen that was easily palpable at presentation, but he seemed to be well and did not really have significant other medical issues. Started on a second-generation drug as first-line therapy, so he was started on dasatinib at 100 mg a day and, early on, achieved a very nice response. Hematologically and cytogenetically had a very good response.

Unfortunately, patient doing well, but about a year and a half out begins to show some dyspnea issues, some breathing issues, treated by a local physician for a possible pneumonia/bronchitis even though there wasn’t a lot of cough. And it turns out that when we saw him back for his routine testing and had these complaints, he had effusions noted on x-ray. So we were faced with the idea of he had a very nice response, achieved a major molecular response, doing well, tolerating the drug very nicely, 100 mg a day, but unfortunately had developed effusions.

DR LOVE: So just very, very briefly, I want to go right down the line here and just in 30 seconds or less, what do you think you might do? Dave?

DR STEENSMA: I would try a diuretic to see if it could be managed that way. Many patients are able to continue the drug, especially those with smaller effusions. But if it’s refractory to diuretic therapy, then you need to switch treatment.

DR LOVE: But just to be clear, because to me, in a way, intuitively it seems like, why would you want to go back on it? You have another great drug. Why not switch it? But you would try to treat it symptomatically and restart the dasatinib?

DR STEENSMA: It sounds like this patient is, other than the effusions, tolerating the drug pretty well, achieving milestones, so it’s often a manageable complication. It should be contrasted with pulmonary hypertension, which you definitely have to stop the drug then, if that develops.

DR LOVE: Okay. So you’ve got a 56-year-old otherwise healthy man who’s somewhat dyspneic. How about if he was 65, had hypertension? Maybe you wouldn’t have started it to begin with, but would you still persist on with the dasatinib?

DR STEENSMA: Again, it’s a judgment call. And if a patient responds to a low dose of a diuretic and is otherwise doing well, then I probably would. If they have any trouble with it, as you point out, Neil, there are other good options. And I would switch.

DR LOVE: So Wendy, agree or disagree?

DR STOCK: I usually treat these patients with steroid, because they’re usually pretty symptomatic when it occurs. And my experience with trying to restart, which I’ve tried in several patients, is that it’s not been successful. The effusion re-accumulates. So in my experience it’s not been a particularly successful endeavor to rechallenge. So I would treat with steroid to decrease the effusion, diuretics and then start with a different agent, probably.

DR LOVE: What kind of corticosteroid do you use? How long do you use it for and why? Is there an immunologic basis to this?

DR STOCK: There’s some thought that this is, because of the multitargeted kinase inhibition of these kinase inhibitors and a potential interaction with the pleural epithelium, so an inflammatory response. So steroids have been used and have been recommended and are usually quite effective at quickly reducing the effusion. And you can use them for any number of days, usually several days’ worth of higher-dose steroid. I often use about 40 mg of prednisone daily for several days and the effusion seems to go away. And then with diuretics, and then it gets better on just diuretics, and then I try to either — I have tried to rechallenge, but these days I typically try to switch now, because I’ve had little success with rechallenging. I don't know if you have had success.

DR LOVE: So, Hagop, again, do you try to rechallenge?

DR KANTARJIAN: Yes, I have. I have a different view. What I would do in a patient like this is stop dasatinib, give prednisone 50 mg daily for 3 days, then 25 mg daily for 3 days. I would add an antibiotic, a little bit of furosemide, 20 to 40, repeat the chest x-ray in 1 week. If it’s negative, which it is in most of the cases, then I would retry a lower dose. Usually I start with 20 mg a day if there’s a good cytogenetic response and try to move up to 40 to 50 mg a day. I find that most of my patients do respond. I am of the philosophy that, do not discard a TKI unless you have used it to the longest period of time at an effective dose that doesn’t cause the side effects.

I want to bring the issue of pulmonary hypertension. There are occasional patients who present with shortness of breath. You do the chest x-ray. It’s negative. But then they have a little bit of ascites and lower-extremity edema. And in those patients you have to do an echocardiogram, because what you’ll find often enough is they have high pulmonary, artery and right-sided pressure. In those patients you have to discontinue the dasatinib, because we don’t know what happens in the long run. But I’ve found it mostly reversible. You use also a bit of steroids, sildenafil and other such medications, and they do very well and they go back to their normal state.

DR LOVE: So just to finish out with this patient, what did you do?

DR SMITH: Stopped the drug, tried some diuretics. A week later, the effusions were worse. He actually had the right-sided lung tapped. The left lung was about the same.

DR LOVE: These are transudates, incidentally?

DR SMITH: Yes. And I started bosutinib as a second drug. And he has not had recurrence. I have not had great success with reusing the drug, although I haven’t followed the super low and gradually increasing paradigm that Hagop mentioned. But I’m more concerned that these are sporadic and they can happen long term out. And if I’ve seen one, I’ve had certainly many patients who have had recurrence over 18 months of multiple recurrences off drug. So I have switched drugs when I’ve seen this before.

DR LOVE: Now, just to be clear, though, did you use corticosteroids?

DR SMITH: I did not use steroids. Again, I didn’t follow the immediate Kantarjian pathway of steroids and diuresis. But I will consider it next time for sure.

DR KANTARJIAN: I’ve noticed that they happen sporadically, but usually it’s after some kind of lung injury. So we see them following the flu season. And I think they are immune mediated. I think the same activated T lymphocytes that happen in those patients are the lymphocytes that go and cause the pleural effusions and the pericardial infusions. That’s why I think short courses of steroids help in these patients.

Chronic Lymphocytic Leukemia (CLL)

Chronic Myeloid Leukemia (CML)

Acute Myeloid Leukemia (AML) and Acute Promyelocytic Leukemia (APL)

Myelodysplastic Syndromes (MDS)

Acute Lymphocytic Leukemia (ALL)