Good News on CAL-101: Could this be a breakthrough treatment for CLL?
Today was another Sarah Cannon day. Marian received her sixth weekly infusion of Rituxan (only two more to go). And John had his monthly check-up. They are each in separate clinical trials studying CAL-101.
John just completed his sixth cycle of CAL-101 as single agent after failing Rituxan and then the "gold standard" FCR (chemo). Marian is receiving treatment for the first time at age 78. She is receiving Rituxan in combination with CAL-101. She will complete her eighth week of infusions and her second 28-day-cycle of CAL-101 the week of Thanksgiving. At that point she will be finished with Rituxan, but she will continue taking CAL-101 (orally) for as long as it keeps her CLL under control.
For the benefit of anyone who has not previously read my blog, I will try to briefly bring you up to date.
My husband, John, was diagnosed in June of 2007 after two CBCs - six weeks apart - showed a significantly elevated white count. At that point, he wasn't symptomatic other than being tired and feeling some slight swelling in his neck. All three (white count, tiredness and lymph node swelling) could have been caused by an infection or virus and that was why his primary physician waited six weeks to check again. We saw a local oncologist for the official diagnosis. But I had already started doing exhaustive research and talking to other CLL patients/caregivers online and I knew the value of getting second opinions and being evaluated by a genuine CLL specialist.
I did not feel at ease with the first oncologist because he was much too eager to use chemo right out of the gate (before we even knew all of John's prognostic markers). I had already learned enough to know that there were milder treatments that we could at least try first (with less toxicity). I knew the risks of chemo (including the possibility of transformation). And I knew that since CLL is a chronic illness, there was no urgency for a quick treatment decision. We told him we wanted to go to Mayo for a thorough evaluation by Dr. Clive Zent. (I had already learned the names of many CLL specialists and where they practiced.)
We made a July appt. at Mayo and, while we were waiting for that date to arrive, I learned (through a new CLL friend on a Christian CLL website) that there was a highly respected CLL specialist right here in Nashville at Sarah Cannon Cancer Center (of Centennial Hospital) by the name of Ian Flinn. He had come to Nashville recently from Johns Hopkins. So I made an appt. to see him in August. But we went ahead with our trip to Mayo and John had all of his prognostics done by their lab. I remember being so proud of my CLL knowledge during our visit with Dr. Zent. Absolutely everything he told John about CLL, I already knew from my own quest for information. And he confirmed what I had already been emphasizing to John; that if we had access to a specialist like Dr. Flinn, we should not even consider going to anyone else. He told John that we were very fortunate to have Dr. Flinn right here in Nashville. (And I beamed as he said these things because I had already found Dr. Flinn and made an appt.)
We knew prior to Mayo that John had the 13q14 deletion and was CD38 negative (both good markers). We didn't know his mutation status or his Zap 70 status. I won't try going into too much detail about the markers, but suffice it to say that they are important indicators of the kind of CLL a patient has and whether one can expect a very slow progressing CLL or an aggressive CLL. Knowing one's markers is also an important factor in making the right treatment choices. We found out from Mayo that John was Zap 70 negative (the third good marker of four) and after determining that, Dr. Zent said it was highly unlikely that John's mutation status would come back unmutated. The least desirable marker is the unmutated status. Unmutated patients usually progress faster and don't respond as well to treatments as the mutated patients do. But it's rare for a patient to have the three good markers John has and be unmutated.
I came home from Mayo just certain that John would be mutated and have the most benign form of CLL. But when the test results came, we found out that he was indeed unmutated. It was probably a bigger disappointment for me because I was the one with all the CLL knowledge. I have dealt with his CLL by learning all I can. John deals with it by not thinking about it and just living his life.
Dr. Flinn agreed that there was no urgency to treat John at diagnosis. We could wait. John successfully avoided any kind of treatment for the first year. But his lymph nodes were swelling and he had fatigue. In the summer of 2008 we decided to try Rituxan. It is a monoclonal antibody and is not as toxic as chemotherapy. Dr. Flinn never tried to push us into any particular treatment decisions. And he was supportive of our desire to avoid chemo for as long as possible. But, unfortunately, Rituxan didn't do much for John's lymph nodes. We waited another year before finally deciding to proceed with FCR (Fludarabine, Cytoxan, Rituxan) plus an experimental drug called Lumiliximab.
FCR is considered the "gold standard" treatment for CLL at this point in time. But it comes with risks and side effects. (Those are all available online and I won't list them in this post.) While it's true that many patients get long remissions from FCR (I read last night about a patient who is still in remission after receiving FCR in 2001), there are also patients who relapse quickly or even fail it completely. And I know of at least one CLL patient who said the decision to use Fludarabine is one she regrets; she says it left her with the immune system of an AIDs patient and gave her only a partial remission. My biggest fear was that John would suffer negative consequences of FCR without getting the positive results. But I tried to be upbeat and positive and expect the long remission. Unfortunately, John failed FCR within a few months of treatment ending (the last week of January 2010).
The more you learn, the more you feel the weight of your treatment decisions. As caregiver, I felt the weight of trying to help my husband make informed decisions. And sometimes that feels harder than if I was making them for myself. He is the patient, it's his body and ultimately the decisions are his (not mine). But I feel such a responsibility to make sure that he does not make uninformed decisions. And it is sometimes hard to know how much information I should share. I don't want to be overly negative (doom and gloom) as much as I don't want him to go into any option uninformed of the potential consequences (which cannot be undone).
Shortly after John's diagnosis, his mom was diagnosed with CLL also. So now I carry the weight of Marian's "informed choices" on my shoulders as well. I take my role as patient advocate very seriously. Marian stayed in "watch and wait" status for a little over two years. But her numbers have gradually moved in the wrong direction ever since diagnosis. And in September she decided to enter a clinical trial with CAL-101 and Rituxan that was being offered to older patients who were previously untreated for their CLL. (John's clinical trial was specifically for patients who had relapsed or failed traditional therapies.) She wanted to avoid the toxicity and immuno-suppression of Fludarabine and by the time she was in the position to make her own treatment decision, John had already completed four cycles of CAL-101 with impressive results. That made her decision a little easier.
CAL-101 has been like a miracle drug for John. He is on the lowest prescribed dose (50 mg.) and his entire therapy consists of taking one pill in the morning and one pill at night. Within two days of taking CAL-101, there was a visible reduction in his lymph nodes. He just had another set of CT scans this week and the nodes are continuing to shrink. They have not been visible or palpable for quite a while. But the scans give exact measurements to undetectable nodes. Many CLL patients experience an initial increase in their white count during the first few months of CAL-101. But John's white count did not increase. All of his counts are normal. His immune system seems to be in good shape (normal neutrophils) and he has not suffered any infections or even a virus during or following chemotherapy. I am so thankful for that.
At John's last office visit, Dr. Flinn revisited the subject of stem cell transplant. I knew he was just trying to establish a "Plan B" if CAL-101 did not prove to be successful longterm. It's early in the clinical trial process. But it still caused me anxiety. That particular day, John's sister was having a consultation at Vanderbilt for her very aggressive throat cancer and John's mom was just starting treatment for her CLL. I was having an "I can't cope with all of this happening at once" moment of fragility. Of course, I will cope with whatever I have to because there really isn't a choice. But it's kind of like hitting transition in labor. Even though I knew I had no choice, I remember thinking, "I can't do this! I can't do this!" And then I gave birth.
Last night, John, Marian and I were talking about CAL-101. Marian was saying she hoped it worked and wondered what she would have to do next if it didn't. John said, "Well, obviously Dr. Flinn doesn't expect CAL-101 to keep working or he wouldn't have brought up transplant again." I told him I did not agree. Doctors have to be thinking about Plan B because experimental drugs are unproven drugs. I knew there was no way for Dr. Flinn to know CAL-101 wasn't going to be a breakthrough treatment any more than he could know with certainty that it would be the breakthrough we're all hoping for. But just the conversation brought that anxiety back up in me and I went to bed thinking, "How will I possibly take care of both of them if John has to undergo a transplant and Marian has to have chemo?" (I had temporarily forgotten the "one day at a time" mindset and allowed myself to project into the fear of the unknown.)
But I am happy to report that at today's visit, Dr. Flinn was eager to share with us that he'd just returned from a CLL symposium in New York (yesterday) and he was very excited about the results of the CAL-101 trials. He said the response rate is about 80% with a median treatment time of 11 months. Patients are not experiencing toxicity issues with the liver at current dosages. And many of these patients (getting such great responses) have been through many different therapies and relapsed (or failed treatment). He also confirmed that he was only mentioning transplant as a Plan B. And he thought CAL-101 was showing great promise. He is very happy with John's response and is hopeful it will continue.
He also explained that one of the major obstacles with CAL-101 is the fact that it tends to increase white counts (sometimes quite substantially) before it starts to clear the blood. Part of the reason for this is that CAL-101 works first on clearing the lymph nodes and some of those malignant lymphocytes are dumped into the blood. This did not happen for John. I asked if it could be because John is on the lowest dose. He said he didin't think so. He thought it was just the nature of this drug. But to the FDA, an increase in white count over the first few months looks like disease progression. The researchers know that it is not disease progression. It's a characteristic of this drug and it's temporary. But one of the obstacles in getting FDA approval is substantiating that for the FDA. So they are trying to find ways to structure clinical trials that will make their case.
Marian is experiencing the increase in her white count. She is in her second cycle of CAL-101 and she has completed six of her eight weekly Rituxan infusions. I asked Dr. Flinn if there is any reason to be concerned that her white count is not coming down. And he said "No. Absolutely not. It can take months."
This post is really lengthy and I realize that only close friends, family and CLL patients are probably still reading. (And maybe only CLL patients!) But I wanted to be thorough for the benefit of those who land on my blog while searching the Internet for information on CLL and CAL-101.
We met a patient today who is considering the same clinical trial that Marian is enrolled in. She was apprehensive about potential side effects. (You should see the thick stack of paperwork a patient has to read and sign off on prior to entering a clinical trial. Just as with any drug a person takes these days, there are endless "possible" side effects you must be informed of before consenting to treatment.) We shared John's experience with her to help ease her mind and I told her that his mom also has not suffered any side effects and is feeling fine. I was so glad that we could encourage her and help her feel less anxiety about entering treatment. And I hope that by sharing all of this publicly on my blog, maybe someone else will receive the same encouragement.
A lot of people don't understand just how important clinical trials are and how fortunate a patient is to have the opportunity to participate in them. CAL-101 is a cutting edge therapy and might possibly be a real breakthrough in the treatment of CLL. The goal is to develop a treatment that can control/manage CLL over a normal lifespan the way insulin controls and manages diabetes.
Jill Clayburgh (a well known actress) died last week of CLL. She never spoke publicly about her disease, so nobody (outside her family) knew she had it until she passed away. She survived for twenty-one years following her diagnosis. That sounds fantastic until you learn that she was diagnosed at the age of forty-five. Twenty-one years is a long survival. But dying at the age of sixty-six is still too young. There has been a lot of discussion in the CLL online community about whether or not she should have remained silent. She could have helped bring attention to CLL and possibly contributed to funding more research with her celebrity standing. But she also had the same right to privacy that any other citizen has. It was her choice to make. And we have to respect that.
A lot of patients are afforded the luxury of privacy with CLL because they do not look sick. John didn't want to tell people initially. He didn't want to be treated differently. He didn't want to put himself through the "I'm so sorry to hear..." conversations. He didn't want anyone to worry about him. He didn't want to bring attention to himself. He just wanted to live his life as normally as he did prior to his diagnosis. I understood all of his reasons and I respected his need for privacy (even though it increased my emotional struggle to internalize and hide what I was going through; I wound up with shingles and reflux six months following his diagnosis). Over time, John relaxed about people knowing. For one thing, his lymph nodes became so swollen that he really couldn't hide the fact that something was wrong. And his privacy just became less important to him over time. I'm thankful for that because I think there is freedom in not having to keep secrets.
Do I wish Jill Clayburgh had gone public? Yeah. It could have helped a lot of others. But I can't judge her either. All I know is, I'm thankful I have the freedom to be open about our CLL journey. Maybe only a handful of patients will ever stumble onto my blog to find information and emotional support. But it is rewarding to me to know I've helped someone - even one person. I value that more than protecting my privacy. (And I'm not great at silence even if privacy WAS important to me.)
John just completed his sixth cycle of CAL-101 as single agent after failing Rituxan and then the "gold standard" FCR (chemo). Marian is receiving treatment for the first time at age 78. She is receiving Rituxan in combination with CAL-101. She will complete her eighth week of infusions and her second 28-day-cycle of CAL-101 the week of Thanksgiving. At that point she will be finished with Rituxan, but she will continue taking CAL-101 (orally) for as long as it keeps her CLL under control.
For the benefit of anyone who has not previously read my blog, I will try to briefly bring you up to date.
My husband, John, was diagnosed in June of 2007 after two CBCs - six weeks apart - showed a significantly elevated white count. At that point, he wasn't symptomatic other than being tired and feeling some slight swelling in his neck. All three (white count, tiredness and lymph node swelling) could have been caused by an infection or virus and that was why his primary physician waited six weeks to check again. We saw a local oncologist for the official diagnosis. But I had already started doing exhaustive research and talking to other CLL patients/caregivers online and I knew the value of getting second opinions and being evaluated by a genuine CLL specialist.
I did not feel at ease with the first oncologist because he was much too eager to use chemo right out of the gate (before we even knew all of John's prognostic markers). I had already learned enough to know that there were milder treatments that we could at least try first (with less toxicity). I knew the risks of chemo (including the possibility of transformation). And I knew that since CLL is a chronic illness, there was no urgency for a quick treatment decision. We told him we wanted to go to Mayo for a thorough evaluation by Dr. Clive Zent. (I had already learned the names of many CLL specialists and where they practiced.)
We made a July appt. at Mayo and, while we were waiting for that date to arrive, I learned (through a new CLL friend on a Christian CLL website) that there was a highly respected CLL specialist right here in Nashville at Sarah Cannon Cancer Center (of Centennial Hospital) by the name of Ian Flinn. He had come to Nashville recently from Johns Hopkins. So I made an appt. to see him in August. But we went ahead with our trip to Mayo and John had all of his prognostics done by their lab. I remember being so proud of my CLL knowledge during our visit with Dr. Zent. Absolutely everything he told John about CLL, I already knew from my own quest for information. And he confirmed what I had already been emphasizing to John; that if we had access to a specialist like Dr. Flinn, we should not even consider going to anyone else. He told John that we were very fortunate to have Dr. Flinn right here in Nashville. (And I beamed as he said these things because I had already found Dr. Flinn and made an appt.)
We knew prior to Mayo that John had the 13q14 deletion and was CD38 negative (both good markers). We didn't know his mutation status or his Zap 70 status. I won't try going into too much detail about the markers, but suffice it to say that they are important indicators of the kind of CLL a patient has and whether one can expect a very slow progressing CLL or an aggressive CLL. Knowing one's markers is also an important factor in making the right treatment choices. We found out from Mayo that John was Zap 70 negative (the third good marker of four) and after determining that, Dr. Zent said it was highly unlikely that John's mutation status would come back unmutated. The least desirable marker is the unmutated status. Unmutated patients usually progress faster and don't respond as well to treatments as the mutated patients do. But it's rare for a patient to have the three good markers John has and be unmutated.
I came home from Mayo just certain that John would be mutated and have the most benign form of CLL. But when the test results came, we found out that he was indeed unmutated. It was probably a bigger disappointment for me because I was the one with all the CLL knowledge. I have dealt with his CLL by learning all I can. John deals with it by not thinking about it and just living his life.
Dr. Flinn agreed that there was no urgency to treat John at diagnosis. We could wait. John successfully avoided any kind of treatment for the first year. But his lymph nodes were swelling and he had fatigue. In the summer of 2008 we decided to try Rituxan. It is a monoclonal antibody and is not as toxic as chemotherapy. Dr. Flinn never tried to push us into any particular treatment decisions. And he was supportive of our desire to avoid chemo for as long as possible. But, unfortunately, Rituxan didn't do much for John's lymph nodes. We waited another year before finally deciding to proceed with FCR (Fludarabine, Cytoxan, Rituxan) plus an experimental drug called Lumiliximab.
FCR is considered the "gold standard" treatment for CLL at this point in time. But it comes with risks and side effects. (Those are all available online and I won't list them in this post.) While it's true that many patients get long remissions from FCR (I read last night about a patient who is still in remission after receiving FCR in 2001), there are also patients who relapse quickly or even fail it completely. And I know of at least one CLL patient who said the decision to use Fludarabine is one she regrets; she says it left her with the immune system of an AIDs patient and gave her only a partial remission. My biggest fear was that John would suffer negative consequences of FCR without getting the positive results. But I tried to be upbeat and positive and expect the long remission. Unfortunately, John failed FCR within a few months of treatment ending (the last week of January 2010).
The more you learn, the more you feel the weight of your treatment decisions. As caregiver, I felt the weight of trying to help my husband make informed decisions. And sometimes that feels harder than if I was making them for myself. He is the patient, it's his body and ultimately the decisions are his (not mine). But I feel such a responsibility to make sure that he does not make uninformed decisions. And it is sometimes hard to know how much information I should share. I don't want to be overly negative (doom and gloom) as much as I don't want him to go into any option uninformed of the potential consequences (which cannot be undone).
Shortly after John's diagnosis, his mom was diagnosed with CLL also. So now I carry the weight of Marian's "informed choices" on my shoulders as well. I take my role as patient advocate very seriously. Marian stayed in "watch and wait" status for a little over two years. But her numbers have gradually moved in the wrong direction ever since diagnosis. And in September she decided to enter a clinical trial with CAL-101 and Rituxan that was being offered to older patients who were previously untreated for their CLL. (John's clinical trial was specifically for patients who had relapsed or failed traditional therapies.) She wanted to avoid the toxicity and immuno-suppression of Fludarabine and by the time she was in the position to make her own treatment decision, John had already completed four cycles of CAL-101 with impressive results. That made her decision a little easier.
CAL-101 has been like a miracle drug for John. He is on the lowest prescribed dose (50 mg.) and his entire therapy consists of taking one pill in the morning and one pill at night. Within two days of taking CAL-101, there was a visible reduction in his lymph nodes. He just had another set of CT scans this week and the nodes are continuing to shrink. They have not been visible or palpable for quite a while. But the scans give exact measurements to undetectable nodes. Many CLL patients experience an initial increase in their white count during the first few months of CAL-101. But John's white count did not increase. All of his counts are normal. His immune system seems to be in good shape (normal neutrophils) and he has not suffered any infections or even a virus during or following chemotherapy. I am so thankful for that.
At John's last office visit, Dr. Flinn revisited the subject of stem cell transplant. I knew he was just trying to establish a "Plan B" if CAL-101 did not prove to be successful longterm. It's early in the clinical trial process. But it still caused me anxiety. That particular day, John's sister was having a consultation at Vanderbilt for her very aggressive throat cancer and John's mom was just starting treatment for her CLL. I was having an "I can't cope with all of this happening at once" moment of fragility. Of course, I will cope with whatever I have to because there really isn't a choice. But it's kind of like hitting transition in labor. Even though I knew I had no choice, I remember thinking, "I can't do this! I can't do this!" And then I gave birth.
Last night, John, Marian and I were talking about CAL-101. Marian was saying she hoped it worked and wondered what she would have to do next if it didn't. John said, "Well, obviously Dr. Flinn doesn't expect CAL-101 to keep working or he wouldn't have brought up transplant again." I told him I did not agree. Doctors have to be thinking about Plan B because experimental drugs are unproven drugs. I knew there was no way for Dr. Flinn to know CAL-101 wasn't going to be a breakthrough treatment any more than he could know with certainty that it would be the breakthrough we're all hoping for. But just the conversation brought that anxiety back up in me and I went to bed thinking, "How will I possibly take care of both of them if John has to undergo a transplant and Marian has to have chemo?" (I had temporarily forgotten the "one day at a time" mindset and allowed myself to project into the fear of the unknown.)
But I am happy to report that at today's visit, Dr. Flinn was eager to share with us that he'd just returned from a CLL symposium in New York (yesterday) and he was very excited about the results of the CAL-101 trials. He said the response rate is about 80% with a median treatment time of 11 months. Patients are not experiencing toxicity issues with the liver at current dosages. And many of these patients (getting such great responses) have been through many different therapies and relapsed (or failed treatment). He also confirmed that he was only mentioning transplant as a Plan B. And he thought CAL-101 was showing great promise. He is very happy with John's response and is hopeful it will continue.
He also explained that one of the major obstacles with CAL-101 is the fact that it tends to increase white counts (sometimes quite substantially) before it starts to clear the blood. Part of the reason for this is that CAL-101 works first on clearing the lymph nodes and some of those malignant lymphocytes are dumped into the blood. This did not happen for John. I asked if it could be because John is on the lowest dose. He said he didin't think so. He thought it was just the nature of this drug. But to the FDA, an increase in white count over the first few months looks like disease progression. The researchers know that it is not disease progression. It's a characteristic of this drug and it's temporary. But one of the obstacles in getting FDA approval is substantiating that for the FDA. So they are trying to find ways to structure clinical trials that will make their case.
Marian is experiencing the increase in her white count. She is in her second cycle of CAL-101 and she has completed six of her eight weekly Rituxan infusions. I asked Dr. Flinn if there is any reason to be concerned that her white count is not coming down. And he said "No. Absolutely not. It can take months."
This post is really lengthy and I realize that only close friends, family and CLL patients are probably still reading. (And maybe only CLL patients!) But I wanted to be thorough for the benefit of those who land on my blog while searching the Internet for information on CLL and CAL-101.
We met a patient today who is considering the same clinical trial that Marian is enrolled in. She was apprehensive about potential side effects. (You should see the thick stack of paperwork a patient has to read and sign off on prior to entering a clinical trial. Just as with any drug a person takes these days, there are endless "possible" side effects you must be informed of before consenting to treatment.) We shared John's experience with her to help ease her mind and I told her that his mom also has not suffered any side effects and is feeling fine. I was so glad that we could encourage her and help her feel less anxiety about entering treatment. And I hope that by sharing all of this publicly on my blog, maybe someone else will receive the same encouragement.
A lot of people don't understand just how important clinical trials are and how fortunate a patient is to have the opportunity to participate in them. CAL-101 is a cutting edge therapy and might possibly be a real breakthrough in the treatment of CLL. The goal is to develop a treatment that can control/manage CLL over a normal lifespan the way insulin controls and manages diabetes.
Jill Clayburgh (a well known actress) died last week of CLL. She never spoke publicly about her disease, so nobody (outside her family) knew she had it until she passed away. She survived for twenty-one years following her diagnosis. That sounds fantastic until you learn that she was diagnosed at the age of forty-five. Twenty-one years is a long survival. But dying at the age of sixty-six is still too young. There has been a lot of discussion in the CLL online community about whether or not she should have remained silent. She could have helped bring attention to CLL and possibly contributed to funding more research with her celebrity standing. But she also had the same right to privacy that any other citizen has. It was her choice to make. And we have to respect that.
A lot of patients are afforded the luxury of privacy with CLL because they do not look sick. John didn't want to tell people initially. He didn't want to be treated differently. He didn't want to put himself through the "I'm so sorry to hear..." conversations. He didn't want anyone to worry about him. He didn't want to bring attention to himself. He just wanted to live his life as normally as he did prior to his diagnosis. I understood all of his reasons and I respected his need for privacy (even though it increased my emotional struggle to internalize and hide what I was going through; I wound up with shingles and reflux six months following his diagnosis). Over time, John relaxed about people knowing. For one thing, his lymph nodes became so swollen that he really couldn't hide the fact that something was wrong. And his privacy just became less important to him over time. I'm thankful for that because I think there is freedom in not having to keep secrets.
Do I wish Jill Clayburgh had gone public? Yeah. It could have helped a lot of others. But I can't judge her either. All I know is, I'm thankful I have the freedom to be open about our CLL journey. Maybe only a handful of patients will ever stumble onto my blog to find information and emotional support. But it is rewarding to me to know I've helped someone - even one person. I value that more than protecting my privacy. (And I'm not great at silence even if privacy WAS important to me.)
Comments
Love & Prayers,
Deb Light
www.cllcfriends.com
We Love You!
Michael and Norma
Heléne
Helene, nice to hear from you. I really enjoy hearing from other CLLers and caregivers. Thank you for taking the time to respond.