Novantrone and Leukemia and Greater Heart Damage Risk

[daisy]

My husband was diagnosed in early September 2008 as having Acute Myelogenous Leukemia (AML) Secondary to administration of Novantrone.

There are three other patients on his hospital floor with the same problem. I think that the public has been underquoted the risk. If the risk that the Novantrone mfg quoted to doctors was 1 in 1000 (as I am told), I actually calculated the risks from their small lot of studies as 1 in 400 patients. If 3 patients in one hospital have the same problem - Novantrone induced AML what must the true risk be?

Also, we received from the medical director of the MS institute that administered the Novantrone a "sorry but the data now shows that Novantrone can harm your heart long after you stop taking it so you will now need to have a heart scan once a year for life" letter about two weeks ago.

[NHE]

Daisy,
Thank you for sharing this information with the ThisIsMS community. Hopefully, it will be helpful for others who may be weighing the risks vs. benefits of potential treatment with Novantrone.

NHE

[weeble]

Hi Daisy. I am very sorry to hear this news about your husband. From the literature I've read, they are saying the risk of AML from Novantrone is 1/400 or 0.25% or 2.5/1000.

I agree that this is somehow being underplayed or overlooked but I did find that info readily online at http://www.rxlist.com/novantrone-drug.htm

Secondary acute myelogenous leukemia (AML) has been reported in multiple sclerosis and cancer patients treated with mitoxantrone. In a cohort of mitoxantrone treated MS patients followed for varying periods of time, an elevated leukemia risk of 0.25% (2/802) has been observed. Postmarketing cases of secondary AML have also been reported. In 1774 patients with breast cancer who received NOVANTRONE® concomitantly with other cytotoxic agents and radiotherapy, the cumulative risk of developing treatment-related AML, was estimated as 1.1% and 1.6% at 5 and 10 years, respectively (see WARNINGS section). Secondary acute myelogenous leukemia (AML) has been reported in cancer patients treated with anthracyclines. NOVANTRONE® is an anthracenedione, a related drug.
The occurrence of refractory secondary leukemia is more common when anthracyclines are given in combination with DNA-damaging antineoplastic agents, when patients have been heavily pretreated with cytotoxic drugs, or when doses of anthracyclines have been escalated.

In July 2008 FDA posted a warning reminding physicians to perform an echo or MUGA prior to EVERY Novantrone infusion and every year after.
http://www.fda.gov/Cder/drug/InfoSheets ... oneHCP.htm

FDA ALERT [7/29/2008]: FDA is informing health care professionals about additional recommendations for cardiac monitoring and reminding of the importance of monitoring cardiac function in patients with multiple sclerosis (MS) who are treated with mitoxantrone.

In March 2005, the labeling for mitoxantrone was changed to recommend that left ventricular ejection fraction (LVEF) be evaluated before initiating treatment and prior to administering each dose of mitoxantrone to patients with MS. These changes were established in response to post-marketing reports and case reports in the medical literature that described decreases in LVEF or frank congestive heart failure in patients with multiple sclerosis (MS) who had received cumulative doses of mitoxantrone that were lower than 100 mg/m2.

Since that time, FDA has received information from a post-marketing safety study that demonstrated there is poor adherence to these recommendations in clinical practice. FDA is working with the manufacturers to educate healthcare providers to adhere to cardiac monitoring recommendations for patients with MS.

In addition to adherence to the recommendations made in 2005, FDA and the manufacturers of mitoxantrone are now advising that all patients with MS who have finished treatment with mitoxantrone receive yearly quantitative LVEF evaluation to detect late-occurring cardiac toxicity.

I am going for my first Novantrone infusion in 2 days. I have aggressive SPMS and have failed interferons and Tysabri.

May I ask when your husband started N and how many doses did he receive?

I wish wholeheartedly that your husband can defeat this AML diagnosis. Again I am very sorry and thank you for mentioning this. Everyone gets very afraid of PML but there are lots of dangerous treatments out there.

[nicko]

I know this post hasn't been active for a while but i'll see if I can get a response anyways. I've had 3 doses of novantrone/mitoxantrone. They wanted to give me a 4th. But I read that the risk of leukemia increases when you get over 80mg. I had 3 x 26mg and said enough. althought it seemed to slow my disease down long enough to get copaxone to work some anyways.

I had read in a smaller study that leukemia was not found in anyone below the 80mg mark. Just above. Daisy how many doses did your husband get?

[Algis]

FWIW I also got 3 doses (but I cant recall the dosage) and the Doctors suggested also me to stop there; tho it has been really beneficial for me at that time.

Hope it help.

Be well

[nicko]

My disease is still active, but very very very mild compared to before mitoxantrone and copaxone. I get new patches of numbness every few weeks. But don't seem to get worse and ease up after a few weeks. Also still get waves of fatigue that seem to last a few days to a week. So its still smoldering in the background.

[Camilla]

Have had two doses (12mg) with minimal side effects. Considering a third to try and slow down worsening RRMS.

Like Nicko, from what I have read the worse problems come (leukaemia, cardiac toxicity) in doses over 100mg -- so will avoid that mark!

How did your first infusion go Weebie?

Camilla

[kats]

Hi Everyone,

My son who was 23 yrs of age started having the mitoxantrone. he had 3 doses over 3 months. and 4 dos every three months. 7 in total over 15 months. (12 mg) He seemed to handle it pretty well with not much side effects.
He took the nause a tablets as advised by the neuro. I just want to mention the last dose he did feel sick but managed to not vomit.
This scared us and we stopped the treatment did not use up all the dosages. He still might have 3 to 4 doses left.
Since having the mitox he has not had another relapse and there is no sign of new leasions or disease activity on the mri's since then.
After having the first dose he got a bit better than what he was and has remained the same even though he has had the other 6 doses.
Having the other doses did not make more improvements in his walking.

He still has difficulty walking and is prob 6.5 edss . Uses a Frame.

A neuro is suggesting to have the remaining 3 doses together with copaxone.
Apparently the two in combination work well he could perhaps get better?

However the risks of more mitox is frightening.

Any suggestions ? thoughts on this is welcome.


Cheers
Kats