APL, Information and SupportInspired by Anita’s Journey through Acute Promyelocytic Leukemia

One of the best ways to keep an eye on a subject that you care about is to use Google Alerts. This is a free service that establishes something called a “persistent search” for web pages with keywords that you specify. Google performs a search for the terms that you specify every day and they email links on any “new hits” they find when they occur (each day).

I maintain a Google-Alert search on several terms – one of which is apl leukemia. If something new comes up with APL, Google emails me an alert with a link to the APL related news article. This is a source of comfort for me as I really care about the subject but being busy with so many things I can’t necessarily research progress on APL every day.

Today, I received an alert for a new drug that is active against relapsed APL – it is called Tamibarotene or “AM-80″. Tamibarotene is already approved for recurrent APL in Japan and US rights to this drug were recently acquired by a company called Innovive. You can read more about Tamibarotene and Innovive here.

Like so many new drugs for APL (and other cancers), tamibarotene is not a magic bullet. It could be an important drug – but probably not a magic bullet – sort of a “another log on the fire” – or “another brick in the wall” toward an overall improved treatment.

I was able to find one clinical study (performed in Japan) where Tamibarotene was used to treat 39 relapsed APL patients that were initially treated with Retinoic Acid and Chemo. About 60% of the relapsed APL patients that were treated with Tamibarotene achieved a complete remission.

Time will tell if Tamibarotene will evolve into a very helpful drug for APL. In the near term, it will likely evolve into an important alternative to arsenic for treatment of APL. Arsenic may continue to be the best (perhaps by far) treatment for relapsed APL- but what if arsenic doesn’t work for you?

What if Arsenic creates life threatening complications for you or your loved one? Arsenic – that’s poison, right?

Arsenic treatment for relapsed APL is very effective but some people just cannot tolerate it. It is rare, but Arsenic can cause serious heart and/or liver complications. What if you can’t tolerate Arsenic? You need an alternative – maybe something like tamibarotine.

When Anita relapsed, I knew she would have to take arsenic to try and get back into remission. I remember being very concerned about whether Anita would be able to tolerate Arsenic. When you read about Arsenic for relapsed APL, you quickly learn that there aren’t any great established alternatives.

It is rare, but some people suffer very dangerous heart complications and some (also rare) suffer very serious and sometimes fatal liver complications. My thought was, what will happen if Anita can’t take arsenic- then what? Luckily, she tolerated it well so this was not a concern.

Still though – what about patients that cannot tolerate arsenic? Drugs like Tamibarotene might help – possibly providing an important alternative that could extend life.

Maybe there will be a few patients that cannot tolerate Arsenic will achieve remission with Tamibarotene. Maybe some of these same patients will then go onto a potentially curative transplant. I think that over time this sort of outcome is likely at least for some APL patients.

Anyhow, reading about Tamibarotene got me thinking about the importance of alternative treatments and drugs – leading to this quick post.

Clinical experience with a new synthetic retinoid, tamibarotene (Am-80) for relapsed or refractory acute promyelocytic leukemia

[Article in Japanese]
Takeuchi M.
Division of Hematology, National Hospital Organization Minami-Okayama Medical Center.

A new synthetic retinoid, Am-80 is expected to overcome all-trans retinoic acid (ATRA) resistance, because of several times more potent differentiation activity than ATRA and sustained plasma level during continuous administration due to a lower affinity for cellular retinoic acid binding protein.

In a preliminary study in Japan, 14 (58%) of 24 acute promyelocytic leukemia (APL) patients who had relapsed from ATRA induced complete remission (CR) achieved a second CR. Of these 14 CR patients, 4 of 6 who underwent allogeneic stem cell transplantation (SCT) are alive, and 4 of 8 patients who received only chemotherapy are alive without relapse for >4 years. Adverse events include xerosis, cheilitis, hyperlipidemia and so on, but these were generally milder than ATRA. In a phase 2 clinical trial, 25 (61%) of 41 patients entered CR.

Among 23 first relapsed patients, 18 (78.3%) patients entered CR, indicating excellent salvage effects for ATRA-relapsed patients. Am-80 may improve disease free survival when used as remission induction and/or maintenance therapy, and it may be effective for relapse from ATRA-induced remission and be curative for patients who receive SCT or intensive post remission chemotherapy.

* A friend of mine asked my how Anita is doing. Here is a copy of the update I sent her.

Dear Jill,

Thanks for asking about Anita.

Anita is doing fine right now. Looking at her you certainly cannot tell she is fighting leukemia.

From my reading, Arsenic treatment for APL often has very few (sometimes none) side effects. Dr.’s have learned how to administer it pretty safely and usually now they can steer clear of any very difficult risks with Arsenic for APL.

We visited City of Hope last Friday for a consultation and we were very impressed with the facility and staff. The grounds are huge, almost a full square mile with many gardens and a lot of interesting artwork everywhere. Our visit was to get setup for Anita’s VAD (central line – essentially a semi permanent IV line).

When we visited COH, I was really impressed by all the donor plaques everywhere. So many people have donated to COH – some famous and most not so famous people. Seeing all the plaques and the evidence of generosity that built COH gave me some strength – feeling the support of all the people that have come “before us.” There are all over plaques at COH from the early 20th century all the way to very recent donations.

I was super impressed with the new Helford Hospital at COH. “The Helford” has two large floors dedicated to transplant patients – very nice modern facility.

Remember the “smiling guy” on the cover of Viking Office Supply catalogs? He would always strike a prominent “game show host” pose on the cover of his company’s office supply catalogs that I dimly remember. Well, that barely memorable guy built a very large company over a period of many years and sold it to Office Depot a while back. His name is Irwin Helford and he gave $36M as a lead donation to help build this new Helford hospital at COH.

The test that is to indicate whether Anita can self donate (AUTO) or will need marrow from her sister still isn’t done. I thought we would get the result from this test on Friday when we visited COH. The delay with the PCR test result is a little bit frustrating because the preparatory treatment for her transplant is to begin here in San Diego on this Friday. I guess they must plan to have the result before treatment begins! We are waiting for something called a “PCR Test” to be finished which will show whether the arsenic treatment was able to clear enough of the cancer to allow for self-donation.

Self donation is a far less dangerous procedure, but it is less protective against relapse so they need to make sure you are very clear of cancer before an self donation transplant is selected. All of Anita’s 7 siblings were tested for donor compatibility and her youngest sister came back as a match. The fact that Anita has a sibling match is a good thing. I expect that Anita will self donate but very important to have a backup plan in case the self donation path doesn’t work out for her.

One thing you might want to check – make sure your health plan allows you to access specialized out of area hospitals. My parents, for example, are on a Scripps HMO and it isn’t at all clear that they would have access to COH if they felt they wanted it someday.
San Diego certainly has some good Dr’s but there is no well established cancer treatment center here – no well established heart transplant facility either. In fact, San Diego’s only heart transplant facility recently suspended operations. I know, hard to think about this stuff when there is (thankfully) no current need!!

Interestingly, Anita’s primary oncologist at Kaiser was telling me that they have been pitched by UCSD Bone-Marrow-Transplant dept which does between 50-80 transplants per year. Kaiser turned UCSD down, preferring instead to go with COH that does between 600-800 BMT’s per year. There is some strength in numbers with a specialized and difficult treatment like this. There are dozens of Dr’s at COH that specialize in transplant medicine. Anita’s COH Dr has been practicing transplant medicine for more than 30 years!

Chris

p.s. The picture was taken about a month ago at the Butterfly exhibit that runs at the San Diego Wild Animal Park each year. Anita is holding a butterfly in her hand that flew off a moment after the picture was taken.