Todd among Patients with Objective Response to AG221

Todd has had two appointments this month, both with good results.  His first appointment was on September 9, 2015, where he had blood work done and an appointment with his doctor and trial study nurse at the Cleveland Clinic.  His counts were great for him:  White count was 2.8; Hemoglobin 10.3; Platelets held steady at 74,000.  Due to the amount of homework I had, Todd drove up and back by himself, so I could get it all done.  He was supposed to "face-time" me with his phone, but forgot!

His second appointment was on September 23, 2015, and like the first, he just had blood work done and a visit with the doctor.  I was able to go with him this appointment so I could talk to his doctor and nurse. (No more relying on him to face-time me!) His results were good:  White count was 2.75; ANCs 2.42; Hemoglobin 9.6; Platelets held steady at 70,000. 

While his numbers are steady and stable, they seem to have reached a plateau.  I discussed these feelings with the doctor and research nurse, asking if his numbers can still go higher at this point or if this was the best they were going to get.  The answer was not as clear as I had hoped.  Basically, anything is possible.  So, there is a chance that they can continue to increase. 

I asked about a broad general comparison of how the other patients in the study at Cleveland Clinic are doing.  Apparently there are 10-12 people on the study there now, but none are having as good of a response as Todd has had.  Many are having a difficult time with the side effects.  The age of patients range from age 39-70+.  Todd's results, in my opinion, have been great!  No transfusions and his increased immunity have been an answer to prayer.  He still suffers from some nausea, fatigue, and diarrhea.  The increased bilirubin is also there, but not as inhibiting as the other side effects. 

I made sure the doctor had a good look at him since he seems to have picked up a virus that is going around.  Two of our kids have seem to have picked it up too.  He looked alright and she did not feel that putting him on antibiotics would be of any benefit.  He is still taking his antiviral medication once per day. We were told to just to watch for symptoms of fever and to be careful not to take anything that could mask a fever. 

I also asked how the study was doing overall and if there was any new data, but there has not really been anything new since some findings in June, 2015, which I will review here.  Nothing new will be out until the American Society of Hematology (ASH) Convention in December 2015. 

From what I have read, as of June, 2015, the patient on the drug the longest at that point was 15 months.  As this drug mainly targets Acute Myeloid Leukemia (AML) patients, it was interesting for me to see the response rate in patients, like Todd, who have MDS.  According to an Agios Press Release from June 12, 2015, "of the 14 patients with myelodysplastic syndrome (MDS), seven achieved an objective response, including two CRs, one CRp and four mCRs."  (Agios, June 12, 2015, np). CR is complete remission.  CRp is incomplete platelet recovery.  mCR is marrow complete remission.  So, I would say that Todd is likely in that 7 who have achieved an objective response.

I'm anxious to see what the results will be in December, when the next set of numbers are released.  I listened to an audio interview with Chris Bowden, M.D., Chief Medical Officer with Agios Pharmaceuticals at the Caaccord Genuity 35th Annual Growth Conference, August 12-13, 2015, Boston MA.  He said that AG221 is the first drug to be approved for AML in several decades (Bowden, August 2015, minute 3:45).  He describes the urgency for relapsed patients to receive treatment, as their condition is in "dire straights" and I couldn't agree more.  That's exactly how I would have described Todd's condition earlier this year. 

Bowden continues to discuss AML later in the interview, stating that there is a real possibility of doctors sequencing every patient's genome at the time of diagnosis to see what kind of gene mutations they are dealing with. Then, the doctor can evaluate what drugs are out there that can be used to treat that specific mutation.  He feels that doctors will be trying to determine the IDH status of their patients at diagnosis and in treatment.  (Bowden, August 2015, minute 19:30-26:07).

You may be asking why all the information about AML when Todd has MDS.  Well, the two are closely related blood cancers.  The main difference is the amount of blast cells used to classify them.  About 30% or roughly 1/3 of all MDS patients will progress to AML.  The diagnosis of AML is given when the patient has blasts cells of 20% or higher.  Thank God Todd's blast cells have never reached that level. 

I just wanted to give this quick medical update and will discuss personal notes in a later post.  Thanks.

References:

Agios.  Press Release.  June 12, 2015.  Web.  Retrieved from: http://investor.agios.com/phoenix.zhtml?c=251862&p=irol-newsArticle&ID=2058805

 Chris Bowden.  Audio Interview. Caaccord Genuity 35th Annual Growth Conference, August 12-13, 2015, Boston MA.  Web. Minutes 0:00-6:10; Minute 19:30.  Retrieved from: http://wsw.com/webcast/canaccord18/agio/index.aspx
Minute 19:30+






http://www.businesswire.com/news/home/20150612005174/en/Agios-Announces-Data-Ongoing-Phase-1-Dose#.Vgg9k5frTm4

http://www.reuters.com/article/2015/06/12/agios-leukemia-idUSL1N0YX2TI20150612
longest MDS patient on drug 16 months in June 2015

Hematological Response: End of Cycle 1 of AG-221

Todd reached a major milestone this past week, where he completed 28 days or the First Cycle of the trial drug study for AG-221.  The Research Team kicked-off Day 1, Cycle 2, the following day, Thursday, May 21, 2015 with the standard 10 hours of blood draws, EKG, and another bone marrow biopsy at the Cleveland Clinic's Taussig Cancer Center. 

The results at the end of just one cycle on the trial drug have been amazing!  His blood counts have come up enough to go 4 weeks without needing a blood transfusion and his immune system has come up to allow him to go off antibiotics, get off the neutropenic diet, and live a little less restrictively for fear of getting an infection that could be deadly.  It is also allowed the team to schedule to have his Hickman Central Catheter removed on the next visit.  They have been wanting to take it out for fear of it causing an infection, but his immune system has been too low.  Now, however, they feel it is strong enough to handle having the Hickman removed and having a port put in on the other side of his chest.  His platelets are still under the recommended 50,000 for having this procedure done, but they will give him a unit of platelets during the procedure to help counteract any possible bleeding complications.  If you have never seen someone with a port, it is a button-sized device that goes into a central vein, under the skin.  So, when they need to draw blood, or give him an injection, the needle will go through the skin.  Here is a brief overview of catheters and ports.  He will have a catheter removed and an port put in:  Port information.

Just to give you a comparison of how his counts have improved here is the 4 week difference:
                                4/20      4/30      5/7      5/14     5/21/15
Hemoglobin:              7.6       8.5       8.7       8.6         9.0  (low still: normal range 13.0 min.)
White:                         .47       .83     1.47     2.03      2.92 (low still; normal range 3.7 min.)
ANCs/Neutrophils:     00        .53     1.07     1.66      2.39 (now falls in lower end of normal)
Platelets: (1000s)         34        41     38         36         35   (Low still normal 150,000 min,)
Bilirubin(total):            n/a      3.8     3.9       3.0        2.6  (want to drop; normal 0.0-1.5)


This is amazing!  In just one cycle, he has seen this much improvement! You can see how he is no longer  Neutropenic (when ANCs/neutrophils are .50 or lower) or no longer needs Transfusions (thresholds for Todd was 8.0 or lower). The elevated bilirubin is caused by the drug, however, you can see the numbers are dropping as his body adjusts better to the medication.  The Indirect bilirubin numbers are fine and the research team is not worried about the elevated total bilirubin, as it would take his number to be 5x the normal or at 7.5 before they would adjust the dosage or make a change in his trial protocol.  The only side effect of the higher bilirubin has been some jaundice, especially in his eyes. 

The best news is, that the first bone marrow biopsy from Day 15, cycle 1, showed a normal range of blast cells in the bone marrow itself.  There was still signs of diseased cell (ringed blasts), but the drug is helping to block the mutation to allow his blood cells to mature, leaving less blast cells in the marrow.  There is also still chromosomal abnormalities found in the cytogenics results, which still show he is having the 5q deletion. 

He had a second bone marrow biopsy done on Day 1, Cycle 2, but we have not received any results back from those yet.  I asked the doctor if he would be considered to show a "response" or if they could say he was in remission, but she made it clear that Todd still has a way to go to ever say he would be in remission.  Under the drug protocol, there are established guidelines for what constitutes a "partial response,"  a "complete response," or "remission."  She stated that Todd would always have the diagnosis of MDS, actually relapsed MDS, that it would never go away.  The only "curative" treatment was the transplant, and that failed.  So, he cannot be "cured" of the disease at this time, but who is to say that there won't be a new curative treatment in the future.  Research and technology are moving so fast in this field, that anything can change in a year.  For example, this drug and the trials were not available a year ago! 

I guess it would take not seeing any blast cells, any chromosomal deletions, and for his counts to be at a certain level before they can use the word remission.  While he is not there yet, it is early in the treatment, and I feel confident that he can at least reach the level of a partial response soon. 

The doctor will not categorize the results as anything but they can see that the drug has produced a "hematological response.*"  

I'm not sure if his blood counts will ever be "normal" again, but I think they can be close to it, or maybe on the low side of normal someday.  In the meantime, he will still suffer from fatigue, some weakness, with a limited lifestyle or activity level, but he has already been forced to adjust to this. 

I honestly feel so relieved that I don't doubt that he is getting better!  While most of his counts are still below normal, we have already achieved the two main goals Dr. Stein, from Memorial Sloan Kettering Cancer Center in New York City, had in mind for Todd:  to lessen his transfusions (which were 6-12 days apart) or to NOT BE transfusion dependent, and to NOT BE neutropenic.  The idea that they now hope to remove his Hickman catheter and put in a port is wonderful!  That means I won't have to flush his catheter lumen's every night, change his bandage and line caps once a week!  He will only need to have the port flushed monthly.  I'm not sure if that is something I will have to do, or whether a nurse will do it at his appointments.  He will also be able to shower without covering it, and hopefully swim this summer!

Since he has he not been transfusion dependent, we haven't had to run to the local oncologist's office once or twice a week to have a CBC drawn to check his blood counts.  That's a lot less running! 

The first cycle of the study was a bit demanding on our schedule, having to go to Cleveland Clinic every week, and sometimes stay for 3 days, but that is behind us now.  With the start of the second cycle, we only have to be there on Day 1, which we just did on May 21, and on Day 15 for a short visit!  The same goes for Cycle 3.  Day 1 will be a long 10-12 hour day (which will be mean a 3 day stay) and then he only has a short visit again on Day 15.  After Cycle 3, he only has to go on the first day of each cycle from there on out! These days will be the long 10-12 days again, but we might be able to resume a more "normal" routine when all of these appointments are no longer necessary. All this is assuming that the drug continues to help and Todd responds positively to it, but I feel confident it will! 

Todd began seeing a physical therapist finally for his shoulder stiffness and pain.  It has helped some, but he still limited in using it.  Our chiropractor had seen Todd before the transplant and then after, was in shock seeing how much muscle mass Todd has lost all over, but especially in his arm and shoulder.  He felt that without the lack of muscle to help support the shoulder, it was making it harder for Todd to use it. Please continue to pray he will find some relief from this pain.  It does inhibit his activity quite a bit and he can only take prescription pain medications, instead of any ibuprofen, and he doesn't like to take them and they don't seem to help as much as he would like.  It wouldn't hurt if he could put on some weight or at least stop loosing it.

So, his next visit at the Cleveland Clinic will be June 4, 2015.  

Family News
Wow, a lot has happened here too!  Hannah Lewis graduates this Saturday!  We've had multiple year-end award assemblies, choir concerts, etc. to attend.  I have been cleaning like mad, with the help of my many good friends and family (Pam, Vicki, Darsie, Dana, Lynda, Mom)!  Two of Todd's friends from work came over and painted one of the garages for him (thanks Chris and Pat). 

We were able to put our house on the market for sale this past week.  It is all bittersweet.  We know it has to go, but we will be sad to leave it as it has been a labor of love building it, finishing it, and living in it these past 12 years.  Please pray for a buyer, for financing so we can purchase a smaller home, and for the entire selling/buying/moving process.

Two praises regarding finishing my Master Degree: I was able to find a practicum at the University of Dayton in the Library/Archives department starting this fall. I have to submit a lot of paperwork to Kent State in the new few weeks to get it ready, but hopefully everything will work out so I can begin in the fall.  I start my summer class and workshop next month!  So, I am hoping I will be able to juggle everything once that starts.  Second, I was able to get into the class I needed for the fall semester.  I was originally on a wait list, but Kent State contacted me last week, offering me an opening in the class!  I needed to take this class to graduate this fall, so now I can apply to graduate in December. 


It's been an emotional roller coaster this past year.  I crave a "normal" life whatever that is!  Change has been the only consistent thing in our lives.  It would be nice to be able to settle down into a mundane routine and stay in one place for awhile.  With our family having to be split-up last fall, with Todd and I in Cleveland, Abby in Cincinnati, Hannah Lewis and Ellie here with my mom, and now having to move from our house into somewhere new, it is a bit traumatic for all of us.  I know it does no good to worry about the timing, and wondering who will buy our house and when, or where we will move and when, but I still feel there is a sense of dread or a cloud that hangs over me.  It is hard to convenience myself that it is all somehow punishment for some reason.  If it is not the cancer and Todd's health, or the finances, then it is the uncertainty of "home" that seems to hang over us. For me, it is emotionally fatiguing, this roller coaster ride we find ourselves on.  I just want the ride to stop, so I can get off, sit down, and rest a while.  I'm still suffering from vertigo (literally), and I wonder why?  Life and this world keeps spinning, and I am trying to keep upright, without falling, despite all the obstacles. 

I gave the entire family this little pep talk last year about how God was going to use Dad's cancer, us going to Cleveland, Abby going to college Cincinnati, and Ellie and Hannah Lewis staying here with grandma, to GROW AND STRETCH US in ways we couldn't imagine!  I had forgotten about this until someone reminded me of it recently and gave me my own pep talk in return!  I know that God continues to mold us, refine us, strengthen us, give us insight, compassion, empathy, make us lean, teach us that living with less is more, help us focus on what is really important, and that home, wherever it will be, will be us together as family.  But growing and stretching usually doesn't come without a bit of pain!

Thanks for your love and support.  We appreciate your prayers and generosity, which continues to amaze and bless us!

Reference:
* According to the National CML Society, http://www.nationalcmlsociety.org/living-cml/response
 Hematological Response is a normalization of the blood counts, particularly white blood cell counts. This is the first noticeable indicator that treatment is beginning to work, though not necessarily in the bone marrow. The response can be partial HR (reduction in white cells,but not down to normal range) or complete CHR (white blood count at or below approximately 12,000 white cells/microliter).

Bone marrow biopsy and results

Todd and I went to the Cleveland Clinic on Wednesday, February 18, 2015 for treatment, a bone marrow biopsy, and to see his BMT doctor. We left Dayton around 5:45 am driving through thick snow and slick roads. 

His counts were in the pits, needing another blood transfusion, less than a week since his last one. His hemoglobin was at 7.3; white count was .300 and his ANCS were too low to count. His platelets were hanging in there at 29,000. 

The bone marrow biopsy went fine, but it took hours to get the blood he needed from the blood bank. Apparently, there was an emergency in the ER in which a lot of blood was needed. So all non-life threatening requests had to be stayed. He didn't get to start his first unit of blood until after 4:00 pm. 

Meanwhile, the doctor had to come down to his treatment room for his appointment. There wasn't a lot to discuss until the bone marrow biopsy results were back. We discussed possible scenarios for treatments speculating with what the results could be. We were told to expect her to call with preliminary results by Friday evening, but not to expect a definite treatment regimen until she had a chance to confer with the other BMT doctors at their Monday conference session. 

We got home after 10 pm. Exhausted from the long day. The weather was so bad school had been cancelled back home for our daughters that day. It was cancelled for Thursday too, due to the extremely low temperatures. Our daughter, Abby, at the University of Cincinnati came home to visit since her classes had also been cancelled all week. 

Friday morning we mustered all of our energy and headed to Savannah, GA for a college visit for our daughter Hannah. 

We got the call from his BMT doctor while on the road about 5:30 pm. She told us the preliminary results showed that the chemotherapy Vidaza treatments were able to get his blast counts down from 7% after the transplant to 3% now. We were pleased to hear that even though his counts weren't lower (>1-2%), that they could still proceed with further treatment, most likely a second stem-cell transplant. The possibility of just doing the Donor Lymphocyte Infusion (DLI)  of white T cells would likely not be an option. Instead his doctor is leaning towards the second transplant using some chemotherapy to suppress his original diseased bone marrow, so his brother's additional cells can gain the upper hand. 

She also brought up the trial study option  we talked about earlier, the drug AG 221.  She said that the Cleveland Clinic has been in the process of getting registered to do the study, and that they were hoping to have it available soon enough to treat Todd there. So, needless to say, I'm going to do some more research about this study. 

Overall, I was encouraged by this news and I can't wait to hear the other results of the biopsy as they come in. They are checking his genetics again for the trial criteria, his cytogenetics, and chimerism. I'm anxious to hear her final recommendations too. I'm assuming that if they do the transplant, that it will happen in the next 2-4 weeks. 

Todd reacted to the news differently. The day we were at the hospital and his doctor brought up the trial study, he said it bothered him to hear talk of enrolling him in a trial.  He feels trials are for patients with no other options. Today, his first reaction was to express a desire to do another round of Vidaza. But, I explained that I had read that the sooner a patient has a second stem cell treatment after relapse, the more success they have.  So, I really feel like time is of the essence here. His doctor, I think feels that Vidaza has done what it was meant to do, but that for now they need to proceed to the next treatment. 

I reassured Todd that there are a few options left. The second transplant, another medication Revlimid if he continues to have just the 5q deletion, and the trial. Although the trial sounds scary, many patients have been fortunate to be cured or put into remission by having the advantage of being in one. 

I asked about whether the multiple transfusion would interfere with his treatment options and her answer was no. That most MDS patients need transfusions like this. Todd had just been fortunate enough to not need them early on. The only detriment of the many transfusions is that Todd will accumulate iron in his blood that maybe over heathy limits. I asked about using chelation therapy to remove the excessive iron but she said that most doctors have found that it doesn't help and that at the Cleveland Clinic they don't even monitor his iron levels. It is a concern, because excessive iron can build up over time causing damage to vital organs. I guess, in the BMT doctor's mind though, this is a lesser priority than trying to get rid of the Cancer and/or staying out of danger from the detriments of low blood counts. 

There is so much more to write but I'm already behind in getting this posted. I will try to post again soon about the trial drug, our current financial situation, and other concerns. 

Thanks for your continued support. 

 

Day +84: Biopsy scheduled Today Dec. 9, 2014

On Sunday afternoon, December 7, 2014  Todd received a message from his online "My Chart" that the BMT Team finally scheduled his bone marrow biopsy for Tuesday, December 9. That meant we were going to have to be at the Cleveland four days this week!  This was too much since we have been trying to drive home in between appointments on Mondays and Fridays. This week, however they had scheduled his doctor's appointment on a Wednesday instead of a Monday with 3 treatment appointments Monday, Wednesday, and Friday. I think the schedule was changed due to his doctor's schedule. He hasn't needed a Wednesday appointment since the first week he was out of the hospital. 

Todd decided he wasn't going to go up for his Monday treatment appointment, so I called the doctor's office to rearrange this week's schedule. We decided to drive up on Tuesday for the biopsy and spend the night so we could be there early for his Wednesday treatment and doctor's appointment. 

We won't get the results of the bone marrow biopsy for about 4-7 days and then the cytogenetics will take a few more days longer. They are looking for a few specific things. 

First, that there is bone marrow from the engraftment. If there is no significant amount of engrafted marrow this would likely indicate a failure in the BMT. 

Second, they will look at the chimerism of the cells present: how many are from his own original bone marrow and how many are from his brother's donated marrow that has engrafted. 

Third, they will look to see if there is any disease present (MDS). They can determine this by looking for blast cells and/or the type of blast cells, and how many there are. 

It looks like they are going to do a CBC today and/or tomorrow to check his counts. 

We are expecting good news. We have been praying that God would bless us, and Todd's body specifically. We are praising God in advance for his wondrous mercy. Please continue to pray on his behalf. 

Update: Bone Marrow Biopsy scheduled for Friday, May 23, 2014

We received a call from Todd's bone marrow transplant doctor at The Cleveland Clinic on Tuesday, May 20, 2014.  She was back in town and wanted to review the "game plan" with Todd.  She asked how the first round of Vidaza went and how he was feeling.  She assured us that the low blood counts were indicative of having the Vidaza treatments and that the blood counts would go back up to his typical numbers in time. 

Todd discussed changing our local oncologist and she said that was fine.  She said she wanted to schedule the bone marrow biopsy for next week.  While we were under the impression that she originally wanted to do the biopsy to review the affects, if any, that the Vidaza was having on the progression of Todd's MDS, this isn't the case. Instead, she wants to do a biopsy NOW to make sure that Todd's MDS isn't naturally progressing on its own since the last biopsy.

Todd was discouraged by this.  He hadn't been flooding his body with the soy peptide or nutritional supplements he has been taking the last two years to help keep his body in optimal health. These products, purchased through the company Reliv, have had positive affects on keeping Todd's blast counts down (basically the cancer cells, which are immature and ineffective blood cells that can't function properly). Since he was experiencing nausea and lack of appetite, he had a hard time drinking them. 

His doctor met in conference with the other bone marrow transplant doctors and the consensus was to do another round of Vidaza if his bone marrow results are "stable" which means about the same: 7-9% blast counts and no new chromosomal abnormalities.  If the results show any more progression, there will not be another round of Vidaza.  The bone marrow transplant will continue to be staged and scheduled as soon as possible.

The scheduling office called today and had an opening for this Friday morning for the bone marrow biopsy to be done in Cleveland. So Todd will be going this Friday instead of next week. Results will take several days, with preliminary results by Wednesday, May 28, or Thursday, May 29.

So, we wait.


Notes:

Defining a blast cell:

In a patient with a myelodysplastic syndrome, the blood stem cells (immature cells) do not become healthy red blood cells, white blood cells, or platelets. These immature blood cells, called blasts, do not work the way they should and either die in the bone marrow or soon after they go into the blood. This leaves less room for healthy white blood cells, red blood cells, and platelets to form in the bone marrow. When there are fewer healthy blood cells, infection, anemia, or easy bleeding may occur. (US Gov., web).

For more information about MDS, blood cells, MDS, and to see a diagram of a bone marrow biopsy see:  http://www.cancer.gov/cancertopics/pdq/treatment/myelodysplastic/Patient/page1

In assessing MDS, using the original IPSS scale (International Prognosis Scoring System), the doctors looked at blast cell counts in determining the risk assessment of the progression of the disease.  When the blast cell count reaches 20% or more, it is then considered to be full Acute Myeloid Leukemia.  Since diagnosis, Todd's counts have gone up and down from 2% up to 7% until reaching their highest point of 9% in the first few months of 2014. Now, the MDS community uses the IPSS-R (the Revised International Prognostic Scoring System) which takes more things into consideration, like hemoglobin, absolute neutrophil count, platelets, and cytogenetics and the number of chromosomal abnormalities, in addition to bone marrow blast cell counts.

Todd's doctors were using the 10% blast count as a personal threshold for doing the bone marrow transplant before he started developing chromosomal abnormalities a few months ago.

To learn more about the IPSS and the IPSS-R:

http://www.qxmd.com/calculate-online/hematology/myelodysplastic-syndrome-prognosis-ipss

http://www.mds-foundation.org/ipss-r-calculator/