DR STOCK: I think these are really, really difficult questions. And I think the data are emerging. But at this moment I have a very difficult time recommending, even in my patients in long-term remission, discontinuation without entry into some sort of clinical trial, because I think that the data, as we’re about to talk about, are somewhat emerging that it may not be as easy to discontinue. And it depends very much on very, very careful, exquisitely sensitive monitoring to make sure that it’s safe and that people are actually not progressing with discontinuation. So I think at this point I have not yet recommended it.

It is interesting. Several of my patients have conceived while on drug without telling me that they were about to do so. And there have been series reported of patients having successful pregnancies on imatinib for sure. We don’t recommend it. It happens. And so far in my 3 patients that I’ve taken care of who have done this without my recommendation to go forward, the babies were delivered without any problem. But this is not something that is clear yet, either, and so I find this a very difficult area. And it’s hard to recommend what exactly to do at this time. So you have to have a very careful discussion with your patient.

DR LOVE: But just to be clear, have you actually stopped a woman on treatment to allow her to have a child?

DR STOCK: I have not done that. No.

DR LOVE: David, do you do that?

DR STEENSMA: Not willingly, but sometimes people are so desperate to have a child —

DR LOVE: Do you advise strongly against it?

DR STEENSMA: So I advise strongly against it, but people are going to do what they’re going to do. So I have stopped it in a few patients and monitored them very closely with monthly RT-PCRs and regular visits, and then if the PCR started rising, started pegylated interferon.

DR LOVE: So Hagop, do you do this or do you strongly recommend not to do it?

DR KANTARJIAN: I recommend not to do it, but I do it. Let me give you the scenario. So I’m uncomfortable with the discontinuation strategies, because to me they are an extreme form of noncompliance. So I do not recommend stopping the treatment. I also worry that while most of the molecular relapses happen in the first year or two, there could be 5% of the patients who could be harmed 10 years down the road, because they could develop a sudden transformation when they are not being monitored properly.

Now, when do I do it? The only exception would be a young woman who wants to become pregnant. So then, if I can tuck her safely into a solid molecular-negative state, PCR-negative for more than a year, then I’m willing to hold the treatment, have her become pregnant, deliver the baby and then restart. I think it can now be done reasonably safely.

Wendy mentioned women who get pregnant on the TKIs. I think the data is that even when you stop imatinib in these patients, there were 125 babies and 3 of them had a syndrome of eye, skeletal and kidney malformation. So you have to stop the TKI. And we have no data with the second-generation or the newer TKIs. So if a woman gets pregnant on a TKI, I believe it should be stopped, although I would not recommend an abortion.

DR LOVE: So Doug, I’m curious what your approach is outside a trial setting. Stopping somebody? Stopping in a woman who wants to get pregnant? And what about men who would like to conceive?

DR SMITH: Yes. I have a couple of fascinating cases of women who have wanted to get pregnant very strongly. They’ve elected to stop their medicine, one of whom was PCR-positive at near the major molecular response level. Twenty-one months she remained stable. She carried a healthy pregnancy and wanted to breast feed for a while and the whole bit. So she eventually did show change and she went back on TKI, and she’s responded. That’s one. That’s one interesting case of someone who can remain unstable — or, excuse me, remain very stable with detectable disease throughout the whole time.

That’s one of the things that we’re learning about what discontinuation is, that it’s not clear, really, how to discontinue, how to really monitor and what to do when you see some small changes, because patients will hover around undetectability in and out of our practice on TKI, as well as off TKI. At least there’s been some suggestion that that’s true in small numbers of patients on discontinuation trials.

DR LOVE: How about men?

DR SMITH: Again, I’ve recommended that they not father a child while taking TKIs as well. So yes. There’s the conception, and then there’s the idea of carrying a pregnancy while taking a drug daily, completely recommended. So men who want to father a child, I’ve not wanted them to be on TKI at the time.

DR LOVE: Interesting. Wendy?

DR STOCK: I’ve had a few discussions about this, too. And in a couple of cases, what I’ve done is I’ve discontinued in those patients who are in molecular remission for short periods of time to allow conception to occur. And that’s happened quite successfully in several —

DR LOVE: With men?

DR STOCK: With men. And then restarted the TKI immediately. But during the period where they’re trying to conceive, I’ve told them not to take the drug. Or you can do sperm banking. In one case we did that for a couple of other reasons, actually, but stopped the TKI, several weeks later did sperm banking and started the TKI. And later that patient ended up — his wife conceived with the artificial insemination.

DR KANTARJIAN: I have a different view. I think with men it doesn’t matter at all. We’ve had dozens of pregnancies of partners of men, and they’ve all been normal. In fact, I can recall about 30 to 40 such babies. So in men I don’t worry. I don’t ask them to stop the TKI. If their partners become pregnant, so be it. But I don’t stop the TKI in men.

Chronic Lymphocytic Leukemia (CLL)

Chronic Myeloid Leukemia (CML)

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

Myelodysplastic Syndromes (MDS)

Acute Lymphocytic Leukemia (ALL)