Second round of Campath and having a baby

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Second round of Campath and having a baby

Postby JP » Mon Mar 31, 2008 11:49 pm

Does anyone know the rationale behind the studies administering a second (or third/fourth) round of Campath? Or could anyone formulate a hypothesis?
Why would HiCy be a once-in-a-lifetime thing, and Campath not? Aren’t they both “rebooting” the adaptive immune system (killing all lymphocytes)?

And does anyone know whether you need immunizations again after Campath (bromley? Raven? Lab Rat)? I would think that if it had the same mechanism behind it as HiCy, one would need their childhood immunizations again…

I’m just asking because having received one round of Campath, I would like to start a family (I’m a 29-year old female), and delaying things for another 12 months is not that attractive when you’ve got MS…

By the way, I got Campath outside of trial, so there would not be a ‘false’ dropout in the studies due to my selfishness. I’m also still very mildly affected by MS and very hopeful that I will be able to care for my future children. Furthermore, being outside of trial, I have the theoretical option to postpone the second round of Campath until after pregnancy (knowing that pregnancy is also a bit immunosuppressive, maybe you can just ‘delay’ the timescale?)

And yes, I know I should talk to my doctor yada yada yada, but I’d like your opinion too!
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Postby bromley » Tue Apr 01, 2008 1:26 am

JP,

Yes you should talk to your neuro. I know that at Cambridge there have been women who have had the two doses and then become mothers. I was at Cambridge recently when one of the Campath patients brought in her baby to show the nurses.

I think 2 doses have proved most effective - but of course there isn't long-term data on this yet. Some people have had a third dose - if the disease showed signs of becoming active again.

I had my second dose at the end of last November and have had no relapses since the first dose and good recovery of deficits. I am low on the EDSS. But a man - so can't get pregnant.

You still have plenty of time age-wise. My wife had our first at 34.

My off the record advice (I'm assuming you're British so unlike our Americans cousins won't sue me), is do what the neuro says (I'm guessing have your second dose). And when your blood test results start coming back normal - start baby-making.

All the best

Ian

The immunisation issue has not been discussed with me - given how thorough they are in Cambridge I'm assuming they would have mentioned it if it was an issue. I think HyCy is a bit more toxic.
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Postby JP » Wed Apr 02, 2008 2:15 am

Thanks, bromley!

And yes, I will listen to my neuro. Just wanted to be prepared when discussing the subject (like most of us on this forum).

I’m glad to hear that women have conceived after having been given Campath. I knew that in theory it does not affect the female reproductive system (in contrast to the male system, but that’s only temporarily) but it’s still nice to see it’s for real. HiCy on the other hand makes one infertile I think (at least in oncology settings they have to freeze the sperm or eggs before treatment, isn’t it?).


Anyway, I researched the immunization issue a little bit further. I found a lot of information in the scientific discussion for EMEA approval of alemtuzumab for B-CLL, with the following on immunizations (p7):

The potential immunosuppressive effect was investigated in cynomolgus monkeys vaccinated with live attenuated Simian immunodeficiency virus (SIV). About 14 months later, these animals and nonvaccinated controls received alemtuzumab (cumulative dose 23 mg/kg in 7 days) and on the next day were challenged with wild-type SIV. Despite the profound lymphopenia (99 % depletion of T lymphocytes), the vaccinated animals did not develop viraemia. The non-vaccinated alemtuzumab treated monkeys had the same antibody response as non-treated controls. Lymphoid reserves in extravascular tissues were still sufficient to preserve humoral and cellular memory responses in the vaccinated monkeys and to mount a primary response in the native animals.


That would mean that it does not kill (all of) your memory lymphocytes, so you don’t lose your pre-treatment immunization status. But that would also mean that if we indeed got some auto-immune memory lymphocytes against parts of our myelin, we didn’t get rid of them either…


But maybe there’s some wiggle room left (p5):

Only one acceptable model for the in vivo lymphocytolytic effect of alemtuzumab has been found, the cynomolgus monkey, and it is not ideal, since the CD52 affinity for the antibody is 16 fold lower than in human cells. Experiments were carried out using single and repeated IV and SC doses for up to 30 days.


Making a quick calculation with the above numbers (monkey cumulative dose 23 mg/kg, 16 fold lower affinity (is it correct to divide it??), JP’s cumulative dose 120 mg, and JP’s weight), I still got around 25% more of Campath then the monkeys. Maybe the lower affinity has a more exponential effect rather than linear? Maybe the second course of Campath in MS is to kill the few remaining nasty lymphocytes?

In any case, if you read up on getting immunizations after Campath, the general feeling is that your body may NOT be able to respond normally (contrary to the non-vaccinated Campath monkeys above which responded the same as non-(Campath)-treated controls), although I must admit they use the terms “may” and “medications that cause immunosuppression” and not alemtuzumab/Campath specifically. They simply don't know yet...


Vaccines, killed virus

(because normal defense mechanisms may be suppressed by alemtuzumab therapy, the patient's antibody response to the vaccine may be decreased. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year)

Vaccines, live virus

(because normal defense mechanisms may be suppressed by alemtuzumab therapy, concurrent use with a live virus vaccine may potentiate the replication of the vaccine virus, may increase the side/adverse effects of the vaccine virus, and/or may decrease the patient's antibody response to the vaccine; immunization of these patients should be undertaken only with extreme caution after careful review of the patient's hematologic status and only with the knowledge and consent of the physician managing the alemtuzumab therapy. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year. In addition, immunization with oral poliovirus vaccine should be postponed in persons in close contact with the patient, especially family members)



So, why wouldn’t they have studied the immunization issue already in leukemia? A quick search on the internet revealed this letter from the FDA in which they approve Campath for leukemia (accelerated approval in 2001), provided there would be a study report on the Immunological assessment of the effect of Alemtuzumab therapy on responses to vaccinations for infectious diseases (among other studies) submitted by November 2006.

This presentation (p13 and p26) from 2005 included the above (required?) study under study number CAM203, but somehow even within that presentation the same study number was also given to another phase II-study on the subcutaneous administration of Campath, and if I look up the
study protocol for CAM203 (study still enrolling participants, starting in may 2006 (!)), the immunization issue is not even mentioned in the secondary outcomes! So I got lost there…

To complicate things even further, I stumbled upon this study on alemtuzumab in kidney transplant recipients, which required participants to have had “Received full course of vaccination for hepatitis B virus (HBV), completed at least 6 weeks before transplantation, OR has naturally acquired immunity”.

Whatever…


In the meantime, it could be interesting to check what’s happened to my own specific antibody-producing lymphocytes (against Hep. B for instance, I hated those shots). Maybe I could persuade my neuro to check them in a couple of months. If Genzyme does not want to examine it, I will :-D


By the way I’m not British, just some other European flavour, and rest assured: I won’t be suing you ;-)
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