Results From My Novartis Study!

I’ve been on a study with Novartis for the past year and a half, receiving 300 mg twice daily of Tasigna (Nilotnib). Tasigna is already approved in many countries (including the US) as a treatment for CML patients who have become resistant to Gleevec (Imatinib) but not for newly diagnosed patients. The purpose of the study is to show positive results for the newly diagnosed so that it can be approved for this segment of patients as well.

A couple of weeks ago Novartis released their 12-month results which showed that Tasigna is superior to Gleevec! I’ve had wonderful results (both major molecular response and complete cytogenic response) and had very few side effects, which seems to have been the experience of most of the people on the study. Hopefully it is approved before the end of the 5-year study so that I don’t have to switch over to Gleevec afterwards.

This article on Medical News Today reports:

One of the key effectiveness measures used in the study was called major molecular response (MMR). This is defined as the reduction in levels of the Bcr-Abl protein to less than or equal to 0.1% of the level seen before treatment. MMR is an important measure in CML, as data show that patients who achieve MMR are unlikely to progress to the later stages of the disease.(6) With nilotinib 300mg twice-daily, the rate of MMR at 12 months was twice that of patients receiving imatinib 400mg once-daily (44% vs. 22%, p < 0.0001).(1)

Another effectiveness measure used in the study was called complete cytogenetic response (CCyR). CCyR indicates that no CML cells containing the Ph chromosome can be seen in a sample of bone marrow taken from the patient. 80% of patients achieved CCyR with nilotinib versus 65% with imatinib 400mg once-daily (p < 0.0001).(1) Responses were achieved faster in the nilotinib group than in the imatinib group.(1)

The Inevitable

At this point in the peace-making process with CML, my main concern is that I will one day become resistant to my medication. Sometimes it hits me that I will die from this. It might not be next year or the next five years, but barring some random accident, I will die of CML. And when I think of that, I wonder what that will be like. I know, that sounds really morbid. But I don’t think it can be helped. I think maybe its my brain’s way of preparing itself for my possible future.

I see myself becoming resistant to my medications, then moving on to trying different kinds and new mixtures .. pills, pills, more pills. Side Effects. Good days. Bad days. Maybe a few years of relative comfort and then ultimately I’ll  run out of medication choices. At that point the only option would be chemotherapy and a bone marrow transplant. With that comes a long list of delightful prospects. Nausea. Lethargy. Pain. Hair Loss. Weight Loss. Depression. Anger.  And ultimately either I will be cured or dead. And for those over 29, like me, living through the process is far from guaranteed.

Ugh. See why I can’t go there very often? I start to read news with the hopes of being pleasantly  surprised by new advances and then my mind and emotions just run away with me and suddenly I’m paralyzed by fear. And one thing I know already is that if you have a chronic illness, you can’t afford to be paralyzed for any reason. So you do what you can. Live in denial. Work to get your priorities straight. Make lots of plans.  Travel. Make a list of goals and do your best to achieve them. Find a job that doesn’t eat your soul. Make an effort with your family. See your friends. Love your lover. Hug your pets even when they eat the strap on your new purse. Surround yourself with supportive, empathetic, positive people. And just cross your fingers that by this point in your life you already have a relatively strong list of those types of people.

Well, really I wanted to talk about this stupid article… which isn’t really stupid at all. It’s actually pretty incredible. Scientist have bred a mouse with CML which will allow them to understand and target the leukemia-initiating cells that are able to slip by meds undetected. Poor little mice. They totally get the shaft in this whole thing. But I assure you Mr. Mouse, I appreciate you. Knowing you’re out there “working” with scientist to help me avoid the grim future that my scared little mind imagines, provides me a lot of comfort. If I had your address, I’d send you a top hat and a hunk of cheddar.

(CML) Mutations Are The Worst

Researchers Discover Why Gleevec-Type Drugs Control, But Do Not Eradicate Leukemia

December 8, 2008

Oregon Health & Science University Knight Cancer Institute researchers are closer to understanding why certain chronic myeloid leukemia mutations are not stopped by the revolutionary targeted cancer pill, Gleevec, or similar therapies in that drug family.

Gleevec, also called imatinib, works by shutting down a critical protein, BCR-ABL, which causes leukemia cells to grow uncontrollably. However, Gleevec also affects other proteins, specifically the KIT protein, which exists on the surface of certain cells and binds to a substance that causes them to grow. Researchers wanted to find out if Gleevec’s ability to inhibit KIT in addition to BCR-ABL is an important component in its success in stopping this cancer.

“What we found is that only simultaneous inhibition of both proteins effectively suppresses leukemia cell growth, suggesting that the reason imatinib is so clinically successful may be due to its capacity to inhibit both the cancer-causing BCR-ABL and the complementary protein KIT,” said Amie Corbin, OHSU Knight Cancer Institute senior research scientist.

“Most of the time we consider ‘off-target effects’ such as those seen with imatinib against KIT as detrimental because they may cause side effects. Our study indicates that things are a little more complicated: some off-target effects may actually be critical for the efficacy of the drug,” said Michael Deininger, M.D., Ph.D., associate professor of medicine (hematology/medical oncology), OHSU School of Medicine; head of the Hematologic Malignancies Section, OHSU Knight Cancer Institute; and Scholar of the Leukemia & Lymphoma Society.

Corbin stresses that this finding should not impact patients currently taking the drugs imatinib or the related drugs dasatini or nilotinib. However, patients should check with their physicians if they have any concerns. All three of the drugs target both BCR-ABL and KIT. However, novel drugs against multidrug resistant mutants of BCR-ABL may not be as effective if they don’t also target KIT and this should be considered in pre-clinical drug development.

Researchers also found that while dual BCR-ABL/KIT inhibition was important to suppress the majority of CML cell types that rely on both BCR-ABL and KIT activity, the most primitive CML stem cells that are resistant to imatinib treatment and cause long-term residual disease in imatinib-treated patients were not sensitive to the effects of KIT inhibition.

“This suggests that CML stem cell survival depends on different proteins that are not targets of imatinib and presents a possible explanation for why these cells survive therapy,” Corbin said.

Variables

One of the hardest things I’ve had to deal with since being diagnosed with CML is making peace with the unknown. I think my struggle is illustrated fairly well by the fact that I’ve felt suicidal a few times since July. The idea never lasted long and I was always able to push it away quickly upon realizing the irony of the sistuation: I’m afraid of dying, so I’m going to kill myself. How absurd. I know that plenty of people with chronic ailments “off” themselves, but usually it’s because they are in physical pain. I’m not in physical pain, so what is this all about? I’m guessing it’s about control. It’s about knowing (or falsely believing that you know) your future. The following are a few of the major question marks bouncing around in my skull.

#1 – How will I live my life

This one is the easiest because it is the only one in which I feel I have any control. However, I’ve been surprised at just how hard it has been to decide what I value most. I mean, don’t we think about this on a daily basis? Aren’t we constantly searching to understand what will make us happy? Yes, I think we are. But sitting down and saying, “If I have 2 years left, what do I want? If I have 5 years left, what do I want? If I have 10 years left, what do I want?” is much more difficult. Yet it has been the only way, I’ve found, to really prioritize. And still, I struggle daily to determine what I value and to what degree.

#2 – Will the rest of my life be painless

This is one of the things that disturbed me most about Dawn’s blog (as mentioned in my first post). She had become resistant to leukemia meds and had to receive a bone marrow transplant. She died soon after that. Bone marrow transplants are always dangerous to survival and only become more dangerous as you get older. The age of 32 is considered old by transplant standards. The pictures in Dawn’s blog show  a happy lively girl transform into an unrecognizable version of herself, sick and zombie-like. It seems ridiculous to me now, but I never actually considered that this could happen to me.

#3 – How long will I live

The medications that are currently used for CML are being touted as huge medical “miracles”. Gleevec is only about 6 years old and my med, Tasigna, is about 1 year old. Before these meds were on the market, a CML patient could expect to live roughly 5 years. With these medications a CML patient can expect to live…. nobody knows. This, of course, is the one question that I badgered my oncologist about most. Her answers were always vague, “we hope that you will live a long life” or “you will probably live much longer than you would have  before these medications were invented”. At first, this vagueness allowed me to believe that I would live to be an old eccentric woman with a house full of rabbits. When I happened upon Dawn’s blog, I realized that this is probably not the case. And that “much longer” is still undefined. For now, I am a guinea pig. I take some comfort in knowing that my experience will help future patients have some closure on this issue.

#4 – What is waiting for me on the other side

I’m not going to talk much about this one, for two reasons. One, I think this is a question that people deal with their whole lives, sick or healthy. Two, I’d like to go into more detail about my thoughts on this issue in a future post. I will say that having a chronic illness has given my brain permission to visit this question quite a bit more than I ever have before. I suppose there are the religious types who believe that they know, without a doubt what is on the other side and that it is a wonderful, utopian place. Unfortunately (and fortunately), I am not one of those people.