Magic drug causes remission, what next?
 

I have been on Agios's drug AG221 for 3 weeks.

http://www.xconomy.com/boston/2014/0...st-early-test/

I just received the BMB report from 2 weeks on the drug. My blasts went from 13% to 4%. They consider this to be enough of a remission for a transplant. ANC, WBC, RBC, HCT all remain low but about the same. Platelets fell from ~100 to 40.

Today I saw both the research doctor and the transplant doctor. They agree that I have an option to go for a transplant in 3 weeks, or continue with the AG221 in hopes that my numbers improve along with my chances of a cure with a SCT. They thought both options were good. They can not speculate whether this drug is a cure or it just causes temporary remission.

Side effects seem mild, uric acid and creatinne are slightly out of range due to eliminating the drug in spite of them having me drink 100 oz. of fluid a day.

What would you do in my shoes?

Ray

wow
 

I'm just about speechless after reading that.
Though premature it sounds very exciting. I will have to read up on it more.

Is this just for AML or MDS as well?

excerpt
 

Yes, to your question, but to what extent??? I took this excerpt from the article:

"Agios enrolled 22 patients who have either AML or myelodysplastic syndrome (when the bone marrow doesn’t produce enough healthy blood cells) and an IDH2 mutation, and have failed one to four prior rounds of chemotherapy—very sick patients. "

Ray, Congratulations! - Great news that you were fortunate to get a response. I guess that's your reward for participating in the trial.
Why not ask your Docs what the Pro's and Con's of waiting are.
Whatever path you take it sounds like you're in good hands.
Its hard for someone to put themselves in your shoes but I would be very happy with the results of the AG 221. Are you feeling good or better when taking the drug? I hope so. Maybe the Docs are thinking you might get an even better response with time?, there's a question you might ask. BTW - Everyone is supposed to drink 100 ounces of water a day according to the experts.
All the best to you - Steve

As far as I know I am 1 of 3 MDS patients on AG221. 15% of AML and 5% of MDS patients have the IDH2 mutation.

My plan is to continue the AG221 until I see no further improvement, and not to wait for the start of a relapse before going to transplant. I want the transplant to peak of remission, I am expecting this to be within 6 weeks.

SCT
 

Wonderful Ray!
Kind regards
Birgitta-A

Ray congratulations,
I think this is remarkable news for you considering only 2 weeks have gone by.
At this point if it were me it would just be to early to know and I would follow my doctors. Pretty uncharted waters I would think.
How often will they be performing bmb's and blood work?
Please keep us up to date on your progress.

Here is clinical trials # if anyone wants to look it up. NCT01915498

Personally I wouldn't be rushing to transplant yet - the 30% success rate for transplants would make me consider extremely carefully, especially since you are feeling better and your results seem to have stablised. How often are your bloods being checked? May I ask your age?

Cheryl C,

You bring up an interesting point of when to have the transplant and weighing the risks. In my situation the plan is to get me into the best health possible and at that time have the transplant, rather than waiting until the numbers turn negative (which they will). I have responded very well to the Vidaza and almost all counts are now in the normal range. The problem seems to be that for most people those counts can quickly turn to the abnormal range. It is a tough call with no certainties whichever call a person makes. Such is the life of MDS.

I am A 73 YO male. I went from no problem to MDS RAEB-2 in less than 6 months. I don't know how long because that was the test intervals. I could have happened overnight, but who knows. For the past 3 months my CBC has been pretty stable with HGB 10.2, HCT 33.8, WBC 1.3, ANC .3. My platelets went from 100 to 40 after starting the AG221. AG221 has not changed any of the CBC numbers other than platelets. Blasts have gone from 13% to 4%. I am weighing my options.

Let nature take its course. 50% mortality in 8 months, small chance of living past 2 years.

Vidaza. 19% chance of working. Can cause remission of several months to a few years. Remission length probably short for very high risk cases such as mine. I look at it as a stepping stone for a transplant. AG221 offers better odds.

AG221 looks very promising. It is likely on the leading edge of novel MDS treatments to come. Caused dramatic reduction of blast counts, not much on CBC. It has a scant track record of 6 months. Do I looks at this as a cure or a stepping stone to transplant? In light of my sudden onset of MDS I am concerned about a similar rapid relapse. If I thought AG221 would give me a couple years of quality life I would do it in a heart beat. I am not ready to roll those dice. At present I get BMB every 2 weeks, blood work every week. Starting next month BMB goes to every other month, and blood work every 2 weeks. I would have cut AG221 more slack if I had seen improved CBC.

Transplant offers a 30% chance of a cure, 30% chance of dying in the first year, with the rest of the odds taken by relapse, GVSH disease and other unpleasant niceties.

I am caught between a rock and a hard place. My current thinking is too take the AG221 until I see no more improvement and then do the transplant. I have two healthy sisters who are 10/10 matches.

I would appreciate anyone point out flaws in my logic.

Ray

Sticking with the AG221 as long feasible sounds like a wise strategy, rar.

I totally understand yours and Baillie's reasoning, because I was in your situation in Sept 2011 and opted to go ahead with a BMT at the time as my older brother is compatible. Like you my expected life span at the time was 2 years at the outside. I felt as though I had been let out of jail when my condition improved and stabilised.

Although my WCC has continued to decrease since I was first diagnosed, I've had the time to learn how to look after myself even better and largely avoid infections. I think that it would be much more difficult for you and Baillie as it seems your platelets are a big problem, and there doesn't seem to be much info out there on how to self-manage that. MDS is so individualised isn't it.

Best wishes to you both and may God guide you as you make your decisions. Everyone on this forum will support you no matter what option you choose.

Info about AG-221
 

Hi Ray,
I don't know enough about SCT to discuss the best option for you but when I looked at the abstracts from the EHA Conference I found info about AG-221. You have so use AG-221 as a keyword.
https://b-com.mci-group.com/EventProgramme/EHA19.aspx
Kind regards
Birgitta-A