petition from t315i patients on the web, page-9

At the ODAC meeting, Dr Craig referred to "...the annual incidence of 250 to 300 T315I patients.." (p40 Transcript). Dr Berman referred to "...with 200 to 300 cases, at least in the United States a year...".

I take that to mean (A)US only and (B)new cases. I imagine it includes those that have developed the mutation before treatment, post-imatinib and post-nilotinib/dasatinib.

The total number of new patients that could be treated by omacetaxine would be at least double with ROW included. Total doses would then also depend on survivability under treatment.

I'm pleased to see CML patients and supporters actively voicing their needs. In their position, I'd be hammering down doors if it meant opening up another option.

It was sobering to read a patient's experience when she spoke at the meeting (pp 144-150)...

"My name is Susan Carrow and I'm a patient with CML from Buffalo, New York at Roswell Park Cancer Institute under the care of Dr. Meir Wetzler. I am here today to speak about my experience as a patient. I will always remember May 3rd, 1999. That is the day my doctor confirmed a diagnosis of CML. It was a devastating shock. My biggest concern at that moment was what we were going to do to treat it and if there was any genetic component that I should have to worry about for my children. The good news was that in fact, this would not affect my children. Treatment was another story. At first, I was told that without treatment, I would have three to five years to live. And since it was 1999, Gleevec was still in clinical trial. So the frontline treatment at that time was interferon and ara-C. The unknown was how well I would respond to interferon and ara-C, and it would buy me adequate time to live to see some important milestones that I had set for myself. My goals became very focused. I wanted to see my daughter graduate from college, attending the wedding of my son, and also, my daughter's wedding, and just maybe be with them to welcome their children into this world. To get beyond my journey, all of the HLA testing did not provide a match, so I began interferon and ara-C. We contacted Fred Hutchinson and they expanded the search for worldwide. That search went on for two years, with no match found. That fall, I suffered a grand mal seizure, which I was told was due to high dose of chemo and interferon. The grand mal seizure suffered (sic) in large hematomas on my head that further incapacitated me. However, I was able to stay on treatment and at Christmas 2000, I had finally achieved a complete cytogenetic remission. I had the feeling that I would be able to overcome this disease.
But my response did not hold and by March 2001, I lost my response. We started to manipulate the dose and tried to salvage my response while keeping me healthy enough to tolerate the treatment. I held on from May 2001 and gladly went on to Gleevec.
By Christmas 2001, I had the good fortune of achieving another complete cytogenetic remission. This time, I was almost sure I was somewhat out of the woods. I mean, after all, here was this miracle drug and I was responding to it. It doesn't get much better than that. But, again, my hopes were dashed. By February 2002, I started to lose my response to Gleevec. In June 2002, I went to Duke to explore a cord blood transplant option and tried to stay on Gleevec. In the fall of 2002, I started on the trial for AMN-107. By the spring of 2003, I had achieved another complete cytogenetic remission, and I felt hopeful once again. For the first two months, we held our breath, but I seemed to hold this response, up until six months. Then I started to lose it again. We tried adding some interferon to the treatment, planned to buy more time and see if we could hold a response for some duration. In the fall of 2006, as part of the trial protocol, I had a bone marrow biopsy. The results were heartbreaking. I had developed the dreaded T315I mutation. I stayed on nilotinib until we could find something else for me to try. That something else was an old drug being revived for the exact mutation that I now had, homoharringtonine [ie omacetaxine]. I started on the trial May 13th, 2007. I knew that going on this trial would mean learning how to reconstitute the drug, which was being supplied in powder form, and injecting myself according to the trial schedule. But I was prepared to do anything. I still needed to be here to welcome grandchildren. I was informed that were I a good responder to this treatment, I could stay on the trial for up to 30 months or more and I would follow an induction phase and then a maintenance phase. Being part of this trial, with the trial team working with me, was just what I needed to help me pick up the battle again with this disease. We got off to a precarious start. One of the side effects affected me very much and I worried that I would not be able to tolerate this treatment. But we made it through the first hurdle and I was able to keep up the protocol. My tenacity paid off. I started to respond to treatment. I made it through the induction phase and enjoyed a few months in the maintenance phase, having achieved a complete cytogenetic remission. In the maintenance phase, I lost my response, but with the return to the induction phase dose, I have a partial cytogenetic response, hoping soon to get back to the maintenance phase and full response. Overall, my quality of life has allowed me to welcome three grandchildren, and a very active grandmother that I am. So in fact, I haven't had just one diagnosis of CML. I have had three/four. I am here today telling you this by the grace of great research and people who are committed to providing options and choices for those who are dealing with a type of CML that doesn't respond tyrosine kinase inhibitors. Although there are so few of us, we need all the help we can get. We are not out of the woods with this disease. What does the future hold for me? Maybe this drug will help me reach a stable, sustainable remission. I am currently on a schedule where I inject eight days a month. I have a good quality of life and play an active role in both my children and grandchildren's lives. I am very grateful and always try to take an opportunity like this to not only speak for myself, but for my fellow CML patients who are not here to speak for themselves and need as much help as I do. Please, let's get this approved now. Thank you."... :(

The FDA are in an inenviable position with decisions like this. However, from the transcript you can see why they need robust answers on the mutation test unless the patient faces multiple TKI failure.