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Sprycel & Pregnancy

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#1 jessica19


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Posted 06 April 2012 - 10:46 AM

Hi Everyone,

My names is Jessica and my husband has CML and has been on Sprycel for the last 3 years. He is doing well and in remission at the moment. We do not have children but hope to someday. As most of you searching on this topic know, there is not a lot of data out there. I have seached high and low. I wanted to provide information I received. A friend of mine contacted Bristol-Myers and received some interesting case study information  and I received helpful infro from the LLS. Here is the information they provided me. If anyone has come across any additional information in recent years---please share.

From Bristol-Myers Squib...

"The potential effects of dasatinib on sperm have not been studied. Sexually active male patients taking dasatinib should use adequate contraception. No specific studies have been conducted in animals to evaluate the effects of dasatinib on fertility. Dasatinib caused atrophy/degeneration of the testis in rats and monkeys and an increase in the number of copora lutea in the ovaries in rates at doses producing plasma exposure levels below or close to that anticipated in patients receiving dasatinib therapy.

Case Studies

A poster presentation at the American Society of Hematology, 2008 assessed the effects of dasatinib in 13 female patients who became pregnant, and 9 male patients who conceived children while receiving therapy with dasatinib. The assessment was presented as patient case studies from dasatinib trials and postmarketing reports.

Data was obtained via clinical study reports for 16 patients in phase I-III dasatinib trials and post-marketing surveillance compiled from 6 voluntarily submitted reports from community physicians. Due to the limited data, and the absence of any robust data, the outcomes of this analysis should be interpreted with caution.

The baseline characteristics of the 9 male patients are described in the table below.

(I cant insert the table, so will just put it in as best I can.)

Table. Baseline characteristics of male patients who conceived children whilst on dasatinib therapy.

Patient A - Age (not reported), Disease (not reported), months on dasatinib (not reported), risk factors (not reported)

Patient B - Age (38), Disease (Chronic Phase - Chronic Myeloid Leukaemia), Months on Dasatinib (12), Risk factors (previous cytarabine therapy; partner on oral contraceptive ethinylestradiol)

Patient C - Age (34), Disease (Chronic Phase - Chronic Myeloid leukaemia), Months on Dasatinib (6), Risk factors (previous therapy with hydroxyurea, anagrelide; multiple concomitant medications including influenza vaccine)

Patient D - Age (43), Disease (Blast crisis - chronic myeloid leukaemia), Months on dasatinib (10), Risk factors - (Anemia; bleeding tendency; prior hydroxyurea therapy; concomitant antibiotics)

Patient E - Age (32), Disease - (chronic myeloid leukaemia), Months on dasatinib (not reported), risk factors - (history of GVHD; ex-tabacco use; prior hydroxyurea, interferon and cytarabine therapy)

Patient F - Age (41), Disease - (chronic myeloid leukaemia), months on dasatinib (7), risk factors (psoriasis; sleep apnea; prior interferon therapy; multiple concomitant medications)

Patient G - Age (49), Disease - (Chronic Phase - chronic myeloid leukaemia), Months on dasatinib (8), risk factors (age; alcohol and tabacco use; concomitant furosemide and lorazepam)

Patient H - Age (not reported), disease (not reported) months on dasatinib (1) risk factors (not reported)

Patient I - Age (24), disease (chronic myeloid leukaemia), months on dasatinib (1), risk factors (not reported)

The outcomes of infants born are available for seven of the nine patients. In all cases, normal, healthy infants were born to partners.

Please note that Bristol-Myers Squibb does not recommend the use of Sprycel in any manner that is inconsistent with that described in the full prescribing information. For a complete discussion of Sprycel please refer to the full prescribing information. "

Information I received from the LLS via email when I asked about pregnancy and Sprycel (husband)

Leading key-opinion leaders have addressed the issue of fertility and tyrone kinase inhibitors (TKI drugs such as Sprycel) utilized for CML.  Listed below are remarks taken from various teleconferences sponsored by LLS.  Some of the material will refer to female CML patients but may have relevance for you. (For your reference, Gleevec is imatinib; Sprycel is dasatinib; Tasigna is nilotinib.) 

12/10/08 CML Teleconference----- Women and Men

Carson Jacobi Pattillo,

MPHI wanted to talk about the issue of pregnancy while on imatinib. Is there any new research or any follow-up on patients who have been pregnant and delivered on imatinib? We frequently get that question.

Brian J. Druker, MD

There continues to be more and more experience, as you'd expect over time. There have been a couple of recent publications that question how safe it is for women to conceive while on imatinib therapy. It appears that it's likely safe, but again, it's very small numbers. It looks like some patients can stop their imatinib when they're PCR negative and stay PCR negative for 6 months or more. That means if a woman conceived on imatinib and stopped therapy, she might be able to make it through pregnancy.Is that a recommended course of action? Is that something that we should consider standard?That is a very difficult and lengthy discussion between patient and physician. The patient's desire to maintain good health and have a family, those are competing options. There's not great data that says that it's safe. There's not great data that says that you can't do it. Having said that, I've taken probably a dozen women through pregnancy. Generally, I would counsel women that I'd like them to have a deep remission before they considered it. Once they conceive, I'd have them stop therapy and stay off therapy during pregnancy. Erin Zammett, who is well-known to The Leukemia & Lymphoma Society, has written a book about doing this. There are examples of women who had done this successfully, but it requires veryintense discussions. Dr. Shah, have you had much experience with this?

Neil P. Shah, MD, PhD

It doesn't appear to be clearly toxic. There have been a large proportion of healthy children born, but what people want to know is can we say with confidence that it is safe? We cannot say that at the present time. We cannot safely recommend that patients continue it.Brian J. Druker, MDDo you have any experience with dasatinib?Neil P. Shah, MD, PhDWith dasatinib, there was a poster at the most recent ASH meeting, which described that therewere some healthy children born, but it was just a small number. I don't recall if there were toxicities. I don't have personal experience with patients being pregnant on dasatinib. 

Question 13/ShellyAnd does imatinib impact fertility as far as making it harder for a woman to conceive?Brian J. Druker, MDThere is currently no evidence that any of these drugs affect fertility.  Question 20You've addressed female fertility and pregnancy, but what about young men on imatinib? How safe is it for them to become fathers?

Neil P. Shah, MD, PhD

This has been analyzed in a very small number of cases, and it appears that all the reported children who were born to men who were taking imatinib have been normal, healthy children, but the numbers that have been reported, I believe, may be still in single digits or may be close to a dozen. It appears to be generally safe, but again, we don't know. 

3/26/08 CML Teleconference----Men and Women Eric:

My question is a family planning question. Have you seen any research to indicate that sperm or semen is affected by Gleevec®?

DR. DRUKER: Eric, thanks for the question. I'm always very careful about this answer and the reality is that the experience is quite limited, but the experience we have for men fathering children on Gleevec® is that it appears to be safe. I'm always very careful about that because there may be 50 to 100 men who father children on Gleevec®. There's not an experience of 1,000 or 10,000. So if there are uncommon or rare side effects that might affect an unborn fetus, we've not seen them. But certainly it appears that Gleevec® does not affect male fertility, does not affect sperm production and doesn't have any harmful effects on fetal development.With women, there's even less data. We have had some women who have become pregnant on Gleevec®, have stopped their Gleevec®, and have gone on to deliver healthy babies. There was recently a report looking at a slight increase in birth defects, but because that was an uncontrolled study, it was hard to know whether that was related or unrelated. If a woman does desire to become pregnant, it requires extensive discussion between the treating physician and the patient, having to balance health issues of the woman, health issues of a developing fetus; it's a very, very complicated issue. But having said that, I have taken somewhere between six to ten women through pregnancies with CMLand as I said, it's tricky, but we can do it.

12/13/07 CML Teleconference-----Women and Men

Question 14: Onsite ParticipantFor women who have received a durable response on imatinib and are wishing to become pregnant, do you have any recommendations for those patients?

Neil P. Shah, MD, PhD

That is an excellent question, and it is a question that we have the pleasure of being able to pose more and more these days. The number of known pregnancy outcomes in patients who have taken imatinib that has been reported has been on the order of approximately 125 cases, and of these, a good half were normal live births. It should be mentioned that these were patients who were exposed to imatinib for varying lengths of time, and at varying lengths of gestation or time during the pregnancy. Clearly, it is possible to have some level of exposure and to give birth to a live healthy infant. However, it has also been noted that there has been a higher incidence of birth defects, higher than what would have been expected from the general population.At present, we cannot confidently tell patients that it is safe to continue imatinib therapy if they want to become pregnant. However, we have to weigh the risks and benefits to the patient with that to the fetus, and there are medical options that are available for people who find out they are pregnant. The first recommendation is to immediately stop imatinib. I like to go with interferon to see if that can control the disease. We know that interferon is safe in pregnancy. Hydroxyurea is actually safe beyond the first trimester. Between those 2, we hope to bridge patients until they give birth, and put them back on imatinib therapy and encourage them not to breastfeed. We do not have any data with the second-generation agents at this point to suggest that they may be safe. At the moment, those are the current recommendations.

Eric J. Feldman, MDI

would add, if someone wants to plan a pregnancy, what we have done is to treat patients until they get a complete cytogenetic remission or their best response, and then perhaps switch them; we have done this, switched them to interferon while they are trying to get pregnant. We are not totally happy about going off all therapy because obviously, not everybody gets pregnant at the same rate, so some people could be off therapy for a significant period of time. Whether interferon therapy will reduce the ability to become pregnant, it is possible. I do not know specifically any data in that regard. But that would be one strategy; if someone had actually wanted to plan a pregnancy, they could do that.

Question 17:

JasonMy wife and I are planning on having a family, or starting a family soon. I was diagnosed this April. I got my PCRU status this month, and was wondering what risks there are as far as the father and childbirth, and that kind of thing.

Neil P. Shah, MD, PhD

That is an excellent question. The study that I mentioned earlier looked specifically at women who were taking imatinib and the outcome on pregnancy. From laboratory studies, there are concerns that these drugs may result in chromosomal changes potentially in germ cells. It would be the safest thing to recommend that you not try to conceive while taking imatinib. We know that the time it takes for mature sperm to form is on the order of approximately 2 months, so this may be one of those instances where Dr. Feldman may have experience suggesting interferon or something of that sort. Unfortunately, what we have in terms of clinical data is particularly lacking for people in your situation.

Eric J. Feldman, MD

Most of the interferon that we have used in this way has been for women who want to get pregnant, and I am not sure we have any particular data on men with CML who went off, so I cannot help you with that.

#2 Trey


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Posted 07 April 2012 - 01:48 PM

Drug manufacturers have not studied the issue of TKI drugs and pregnancy, so they take the approach that it is not recommended.  You have probably seen a few reports of childbirth abnormalities when the woman took TKI drugs during pregnancy, but I have not seen any childbirth abnormality issues reported as a result of the male taking TKI drugs.  As you might expect, there are major differences between the male and female effects of TKI drugs during conception and pregnancy. 

Since there is not much research to go on, I will describe some of the issues involved, but the following must be assumed to be conjecture based on what I understand about TKI drugs.  The male delivers 1/2 of the 46 chromosomes needed for pregnancy.  TKI drugs do not affect the actual chromosomes in a cell, only a few of the tyrosine kinases, of which there are over a hundred in the human body.  The TKI drugs will affect cell functions in certain ways, but do not disrupt the chromosomes directly.  So if a male sperm delivers the required chromosomes and it results in a pregnancy, then one would conjecture that the inhibition of the tyrosine kinases in the sperm will have no impact on the chromosomes delivered or on the resulting fetus.  Whether the TKI drug might affect the quantity or motility of the sperm are not much of an issue compared to the health of the fetus, although it may affect probability of success.

The woman, however, is another case (although not your issue, I will discuss it here for others).  The woman must carry the fetus to term, and if taking TKI drugs, those drugs can inhibit the tyrosine kinases in the cells of the fetus.  Tyrosine kinases are important for cellular processes including regulation of cell division.  So it is possible (probability unknown) that TKI drugs could negatively affect the development of a fetus in the womb of a woman taking TKI drugs.  Whether those inhibitions of certain tyrosine kinases are significant enough to harm the fetus, either seriously or minimally, is largely unknown.  So it is wise for a woman to avoid TKI drugs during pregnancy because the fetus will have some of its tyrosine kinases inhibited to at least some degree, which causes some potential for harm.  Sprycel is probably more serious than Tasigna or Gleevec, since it inhibits the SRC family of kinases, while Tasigna and Gleevec do not.   

A possible very conservative approach for the male would be to achieve at least CCyR status, stop the drug for a week prior to ovulation, continuing this one week off per month for as long as it takes. 

There are two docs (Dr Smith and Dr Lishko -- Urology Dept) at UCSF interested in the TKI and pregnancy issue, and you may want to contact them:


#3 jessica19


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Posted 09 April 2012 - 11:35 AM


Thank you very much for this message. I find myself very overwhelmed and your response gave me clarity I have been seeking. I sent Dr. Smith an email regarding more info on his studies.

Again, I truly appreciate it.



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