As many of you know, I write a column for Lymphoma News Today called "Things That Give Me Hope."
You may also know that, over the last year and a half or so, I've tried to step up my advocacy work. A big part of that came from being invited to a conference called HealthEVoices. At the conference (which I've been to twice now), I've met a bunch of other online health advocates. They advocate for all kinds of conditions -- mental health, diabetes, HIV, and about 40 others.
But it was the other cancer advocates that really touched me. It's amazing to be in a room with other people who have heard he words "You have cancer," and realize that all of the things you have thought and felt have also been experienced by others. It's a reminder that you're not alone.
Those experiences came together for my column this month on Lymphoma News Today. It's called "Young People Give Me Hope," and it describes some of the amazing young cancer advocates that I've met.
Young people have incredible energy and creativity. They are fearless. These young cancer survivors have faced horrible things and turned them into wonderful things. They are trying to change the world.
Check out the article, and click the links. You'll see the great things they are doing, and my guess is that it will give you hope, too. you'll see how bright the future is.
Friday, December 21, 2018
Monday, December 17, 2018
CAR-T for NHL
OncLive has an excellent video series on CAR-T. They usually spread their video series over a couple of weeks, with a new installment every few days.
Today's installment is called "Expanding the Role of CAR T in Non-Hodgkin Lymphoma," and it features comments from Dr. Nilanjan Ghosh of the Levin Cancer Institute in North Carolina; Dr. Leo Gordon from Northwestern Memorial Hospital in Chicago; and Dr. Matthew Lunning from the University of Nebraska Medical Center.
This video is fourth in the series. The others cover some basic information about how CAR-T works, and some practical issues like cost. It's a good introduction to CAR-T. (And, of course, if you want to learn more, especially from a patient's perspective, you might consider checking out the CAR-T and Follicualr Non-Hodgkin's Lymphoma blog, run by some folks with first-hand experience as patient and caregiver.)
I found this video on expanding the role of CAR-T especially interesting. In one of the online groups I am in, someone complained this week about not being eligible for CAR-T because her disease wasn't aggressive enough. Lots of grumbling followed. People seemed to think that the treatment was being kept from them unfairly.
That is not the case. A couple of versions of CAR-T have been approved by the FDA, but approval, of course, is always for very specific situations. And for Follicular Lymphoma, that means patients with a particularly aggressive form, who have already tried a certain number of treatments.
There are trials that are looking to expand who can get CAR-T, but it's going to be a little bit of time before we know how well it works for those folks.
This particular video gets into some of the issues that surround making CAR-T available to me people. There are a couple of trials looking at CAR-T after the patient has had a transplant. There are questions about whether CAR-T could work for someone with MRD -- Minimal Residual Disease (in other words, how many cancer cells need to be around for the CAR-T to attack in order for it to work?). Is it better to use this on POD24 patients (those who have the disease come back with 24 months after they have had chemoimmunotherapy)?
Lots of questions about CAR-T, and only time will give us the answers.
My new oncologist, Dr. H, thinks CAR-T will be much more effective in 5 years. We'll have more data from more trials, and we'll get a better sense of just who this treatment will work for. We've had lots of success stories so far (and a few failures). Maybe in 5 years we look forward to more of thsoe successes.
Click above for the video. If the link doesn't work (or if you need a transcript for translation), OncLive provided a very helpful transcript, which I am including below:
Nilanjan Ghosh, MD, PhD: One of the future directions for CAR T-cell therapy in relapsed/refractory B-cell lymphoma is to see if it can be moved up from second-line, and after failure of second-line to an earlier line. It has good activity in most patients, so this is a natural evolution. The question is, can it be compared to transplantation? There are 3 clinical trials that have been planned for this possibility. There’s ZUMA-1, in which axicabtagene ciloleucel [axi-cel] is being compared to salvage therapy followed by transplantation. There’s a trial called BELINDA in which CTL019 [Kymriah] is being compared to salvage therapy followed by transplantation. All these trials are going to see whether patients who are failing first-line therapy, have relapse, and thereafter can receive CAR T-cell products compared to other salvage therapies.
Leo Gordon, MD: The timing of CAR T therapy is an evolution. Currently, it’s for patients with refractory disease, but perhaps consolidation for patients with responding lymphoma who are high risk for relapse would be a good fit. Should it be used as consolidation for patients in complete remission? This begs the question: Do you need antigen in order for this to work? In other words, do you need some tumor present in order for CAR T-cell therapy to work? Will it work with minimal residual disease with no obvious antigens that are there for the CARs to attach to? We do not know the answer.
At the moment all the patients treated have had visible disease on PET [positron emission tomography] scans and physical exams. Whether it works in patients with no obvious disease, we don’t know. Saying it might be used as a consolidation treatment would probably be premature.
As we try and advance the use of these, ultimately the CAR T therapies themselves are going to be better; there are going to be better costimulatory molecules. There’ll be more educated cells that might be targeting a variety of different targets on tumor cells. Additionally, we’re exploring the so-called Platform study, which is being done with Celgene-Juno with the same JCAR017 molecule cell product. We’re looking at the use of adding certain agents to CARs, such as PD-L1 [programmed death-ligand 1] checkpoint inhibitors.
We’re looking at immunomodulatory imide drugs [IMiDs], a variety of other drugs that we think might enhance the efficacy of these CARs, perhaps by reducing the number of T-regulatory cells, which might get in the way of the CARs working. In the future, there are going to be better CARS and costimulatory molecules, and there will be perhaps the use of combinations of treatment—maybe radiation, which will help release antigens and make the CARs more effective radiations to certain sites of disease.
Matthew Lunning, DO: Clinical trials are ongoing in follicular lymphoma, mantle cell lymphoma, and chronic lymphomatic leukemia [CLL] looking at CAR T cells in these spaces. If you take each one of those diseases—it’s a spectrum—it’s just like large B-cell lymphoma. Patients with follicular lymphoma receive an anthracycline-containing bendamustine [Bendeka] regimen, which in the refractory setting is a front-line therapy that becomes more intensive in the second-line setting as the lymphoma progresses. This is an acceptable patient for CAR T-cell therapy, I think, on a clinical trial.
One could argue that a patient who relapses within 2 years from front-line anthracycline-based chemotherapy is a big deal. Fifty percent of those people are not alive in 5 years, and their likely cause of death is lymphoma. That’s a population in follicular lymphoma that I would want to study with CAR T cells. Mantle-cell lymphoma is another population I would like to study. It can definitely behave like the most aggressive lymphomas in the relapsed/refractory setting.
You have to be able to discern which one of these it is behaving like. The same thing goes for CLL. In mantle cell lymphoma, again, if you’ve gotten front-line chemotherapy and consolidated with an autotransplant, and you relapsed quickly after an autotransplant, that might be an area where CAR T-cell treatment would be a reasonable strategy. Some may argue that that patient should at least get a trial of ibrutinib [Imbruvica] tyrosine kinase inhibitor prior to going to CAR T cell.
The answer, if you look at the efficacy that’s been displayed across the 3 constructs, is that if it’s going to work, if it’s agnostic to double-hit or triple-hit refractory in 6 months, or after autotransplant, you can still see responses with durability in that patient population. Even in indolent lymphomas where you’re talking about that tough population, there may be the opportunity for efficacy, but you have to be mindful of the potential toxicity. It’s always a risk-benefit discussion with the patient and family regarding CAR T-cell therapy
Today's installment is called "Expanding the Role of CAR T in Non-Hodgkin Lymphoma," and it features comments from Dr. Nilanjan Ghosh of the Levin Cancer Institute in North Carolina; Dr. Leo Gordon from Northwestern Memorial Hospital in Chicago; and Dr. Matthew Lunning from the University of Nebraska Medical Center.
This video is fourth in the series. The others cover some basic information about how CAR-T works, and some practical issues like cost. It's a good introduction to CAR-T. (And, of course, if you want to learn more, especially from a patient's perspective, you might consider checking out the CAR-T and Follicualr Non-Hodgkin's Lymphoma blog, run by some folks with first-hand experience as patient and caregiver.)
I found this video on expanding the role of CAR-T especially interesting. In one of the online groups I am in, someone complained this week about not being eligible for CAR-T because her disease wasn't aggressive enough. Lots of grumbling followed. People seemed to think that the treatment was being kept from them unfairly.
That is not the case. A couple of versions of CAR-T have been approved by the FDA, but approval, of course, is always for very specific situations. And for Follicular Lymphoma, that means patients with a particularly aggressive form, who have already tried a certain number of treatments.
There are trials that are looking to expand who can get CAR-T, but it's going to be a little bit of time before we know how well it works for those folks.
This particular video gets into some of the issues that surround making CAR-T available to me people. There are a couple of trials looking at CAR-T after the patient has had a transplant. There are questions about whether CAR-T could work for someone with MRD -- Minimal Residual Disease (in other words, how many cancer cells need to be around for the CAR-T to attack in order for it to work?). Is it better to use this on POD24 patients (those who have the disease come back with 24 months after they have had chemoimmunotherapy)?
Lots of questions about CAR-T, and only time will give us the answers.
My new oncologist, Dr. H, thinks CAR-T will be much more effective in 5 years. We'll have more data from more trials, and we'll get a better sense of just who this treatment will work for. We've had lots of success stories so far (and a few failures). Maybe in 5 years we look forward to more of thsoe successes.
Click above for the video. If the link doesn't work (or if you need a transcript for translation), OncLive provided a very helpful transcript, which I am including below:
Nilanjan Ghosh, MD, PhD: One of the future directions for CAR T-cell therapy in relapsed/refractory B-cell lymphoma is to see if it can be moved up from second-line, and after failure of second-line to an earlier line. It has good activity in most patients, so this is a natural evolution. The question is, can it be compared to transplantation? There are 3 clinical trials that have been planned for this possibility. There’s ZUMA-1, in which axicabtagene ciloleucel [axi-cel] is being compared to salvage therapy followed by transplantation. There’s a trial called BELINDA in which CTL019 [Kymriah] is being compared to salvage therapy followed by transplantation. All these trials are going to see whether patients who are failing first-line therapy, have relapse, and thereafter can receive CAR T-cell products compared to other salvage therapies.
Leo Gordon, MD: The timing of CAR T therapy is an evolution. Currently, it’s for patients with refractory disease, but perhaps consolidation for patients with responding lymphoma who are high risk for relapse would be a good fit. Should it be used as consolidation for patients in complete remission? This begs the question: Do you need antigen in order for this to work? In other words, do you need some tumor present in order for CAR T-cell therapy to work? Will it work with minimal residual disease with no obvious antigens that are there for the CARs to attach to? We do not know the answer.
At the moment all the patients treated have had visible disease on PET [positron emission tomography] scans and physical exams. Whether it works in patients with no obvious disease, we don’t know. Saying it might be used as a consolidation treatment would probably be premature.
As we try and advance the use of these, ultimately the CAR T therapies themselves are going to be better; there are going to be better costimulatory molecules. There’ll be more educated cells that might be targeting a variety of different targets on tumor cells. Additionally, we’re exploring the so-called Platform study, which is being done with Celgene-Juno with the same JCAR017 molecule cell product. We’re looking at the use of adding certain agents to CARs, such as PD-L1 [programmed death-ligand 1] checkpoint inhibitors.
We’re looking at immunomodulatory imide drugs [IMiDs], a variety of other drugs that we think might enhance the efficacy of these CARs, perhaps by reducing the number of T-regulatory cells, which might get in the way of the CARs working. In the future, there are going to be better CARS and costimulatory molecules, and there will be perhaps the use of combinations of treatment—maybe radiation, which will help release antigens and make the CARs more effective radiations to certain sites of disease.
Matthew Lunning, DO: Clinical trials are ongoing in follicular lymphoma, mantle cell lymphoma, and chronic lymphomatic leukemia [CLL] looking at CAR T cells in these spaces. If you take each one of those diseases—it’s a spectrum—it’s just like large B-cell lymphoma. Patients with follicular lymphoma receive an anthracycline-containing bendamustine [Bendeka] regimen, which in the refractory setting is a front-line therapy that becomes more intensive in the second-line setting as the lymphoma progresses. This is an acceptable patient for CAR T-cell therapy, I think, on a clinical trial.
One could argue that a patient who relapses within 2 years from front-line anthracycline-based chemotherapy is a big deal. Fifty percent of those people are not alive in 5 years, and their likely cause of death is lymphoma. That’s a population in follicular lymphoma that I would want to study with CAR T cells. Mantle-cell lymphoma is another population I would like to study. It can definitely behave like the most aggressive lymphomas in the relapsed/refractory setting.
You have to be able to discern which one of these it is behaving like. The same thing goes for CLL. In mantle cell lymphoma, again, if you’ve gotten front-line chemotherapy and consolidated with an autotransplant, and you relapsed quickly after an autotransplant, that might be an area where CAR T-cell treatment would be a reasonable strategy. Some may argue that that patient should at least get a trial of ibrutinib [Imbruvica] tyrosine kinase inhibitor prior to going to CAR T cell.
The answer, if you look at the efficacy that’s been displayed across the 3 constructs, is that if it’s going to work, if it’s agnostic to double-hit or triple-hit refractory in 6 months, or after autotransplant, you can still see responses with durability in that patient population. Even in indolent lymphomas where you’re talking about that tough population, there may be the opportunity for efficacy, but you have to be mindful of the potential toxicity. It’s always a risk-benefit discussion with the patient and family regarding CAR T-cell therapy
Wednesday, December 12, 2018
Bispecifics for Follicular Lymphoma
I've mentioned bispecifics in my last two posts, so I thought I'd look into them a little more.
BioPharmaDive published a nice piece last week called "At ASH, Bispecific Cancer Therapies Make a Mark." It does a nice job of explaining what bispecifics are and why they made a mark at ASH.
Maybe the easiest way to understand a bispecific is to compare it to a monoclonal antibody like Rituxan. Rituxan (as you may know) works by looking for a protein on the cancerous B cell called CD20 and attaching itself to it. From there, it can kill off the cell in a few different ways. (Watch this cool animation video to see cancer cells die.)
The important thing here is that the one side of the Rituxan attaches the the cell.
A bispecific works in a similar way, but instead of attaching with one side, it attaches to two -- the the cancer cell on one end (like Rituxan), but to an immune cell on the other. Like Rituxan, one end attaches to the CD20 protein, while the other end attaches to a CD3 protein on the immune cell. In this way, the bispecific brings the two cells together -- the cancer cell and the immune cell that is meant to kill it off.
There were three bispecifics discussed at ASH that target B cell lymphomas. All of them target CD20 on on end and CD3 on the other.
The first is Mosunetuzumab. In its phase 1 trial, 98 patients were enrolled. 55 of them had DLBCL or transformed Follicular Lymphoma, and 29 more had regular old FL. There was a 41% Response Rate (33% for the DLBCL/transformed group, but 61% for the FL group), with 27% having a Complete Response (21% of the Diffuse/transformed group and 50% of the FL group). Side efefcts were tolerable. The responses even came for patients who culd no longer take Rituxan, or who tried CAR-T but did not have success. The median follow-up for the study was a little over a year.
The second one is called REGN1979. It was also tested in a phase 1 trial, with 54 patients (16 of them had FL). A number of patients had to withdraw from the study because it didn't work, and their disease got worse. Phaee 1 trials focus on side effects (again, they were called manageable) and figuring out what the best dose would be. For patients who had a particular dose (more than 5mg), there was a 100% response rate for FL patients (5 Complete and 2 Partial Responses).
The third is RG6026. Again, patients were in a phase 1 clinical trial -- 64 with aggressive B cell lymphomas, including transformed FL, and 17 with FL. Again, at a certain dose (300 µg or above), 3 of 5 FL patients had a Response, with 2 of them having a CR. Side effects were manageable.
One of the issues that is discussed in the abstracts is Cytokine Release Syndrome. This is also a problem with CAR-T treatments. When the body has so much T cell activity, the patient can develop flu-like symptoms, and they can be life-threatening. Researchers were aware of this possibility and took steps to deal with it.
The important thing to remember with these, of course, is that they are all phase 1 studies, and they haven't involved a lot of patients. Larger phase 2 studies will be necessary to figure out if they are as effective as they seem, and then even larger phase 3 studies will really let us know.
(Dr. H, my new oncologist, told me that this kind of treatment might be one that I would want to consider. My new hospital is part of the clinical trial for one of the three treatments.)
Interestingly, according to the BioPharmaDive article, one of the people involved in one of the trials thinks the bispecifics might work even better as part of a combination (which is, of course, the direction that lots of new treatments are going in).
However, another person looking at the results was a lot less impressed after looking at the numbers.
Time will tell. Perhaps one or more of them will move on to a phase 2 trial, and we will see how things go.
For now, though, I'll take my new oncologist's excitement about them as a a good sign, and hope for the best.
BioPharmaDive published a nice piece last week called "At ASH, Bispecific Cancer Therapies Make a Mark." It does a nice job of explaining what bispecifics are and why they made a mark at ASH.
Maybe the easiest way to understand a bispecific is to compare it to a monoclonal antibody like Rituxan. Rituxan (as you may know) works by looking for a protein on the cancerous B cell called CD20 and attaching itself to it. From there, it can kill off the cell in a few different ways. (Watch this cool animation video to see cancer cells die.)
The important thing here is that the one side of the Rituxan attaches the the cell.
A bispecific works in a similar way, but instead of attaching with one side, it attaches to two -- the the cancer cell on one end (like Rituxan), but to an immune cell on the other. Like Rituxan, one end attaches to the CD20 protein, while the other end attaches to a CD3 protein on the immune cell. In this way, the bispecific brings the two cells together -- the cancer cell and the immune cell that is meant to kill it off.
There were three bispecifics discussed at ASH that target B cell lymphomas. All of them target CD20 on on end and CD3 on the other.
The first is Mosunetuzumab. In its phase 1 trial, 98 patients were enrolled. 55 of them had DLBCL or transformed Follicular Lymphoma, and 29 more had regular old FL. There was a 41% Response Rate (33% for the DLBCL/transformed group, but 61% for the FL group), with 27% having a Complete Response (21% of the Diffuse/transformed group and 50% of the FL group). Side efefcts were tolerable. The responses even came for patients who culd no longer take Rituxan, or who tried CAR-T but did not have success. The median follow-up for the study was a little over a year.
The second one is called REGN1979. It was also tested in a phase 1 trial, with 54 patients (16 of them had FL). A number of patients had to withdraw from the study because it didn't work, and their disease got worse. Phaee 1 trials focus on side effects (again, they were called manageable) and figuring out what the best dose would be. For patients who had a particular dose (more than 5mg), there was a 100% response rate for FL patients (5 Complete and 2 Partial Responses).
The third is RG6026. Again, patients were in a phase 1 clinical trial -- 64 with aggressive B cell lymphomas, including transformed FL, and 17 with FL. Again, at a certain dose (300 µg or above), 3 of 5 FL patients had a Response, with 2 of them having a CR. Side effects were manageable.
One of the issues that is discussed in the abstracts is Cytokine Release Syndrome. This is also a problem with CAR-T treatments. When the body has so much T cell activity, the patient can develop flu-like symptoms, and they can be life-threatening. Researchers were aware of this possibility and took steps to deal with it.
The important thing to remember with these, of course, is that they are all phase 1 studies, and they haven't involved a lot of patients. Larger phase 2 studies will be necessary to figure out if they are as effective as they seem, and then even larger phase 3 studies will really let us know.
(Dr. H, my new oncologist, told me that this kind of treatment might be one that I would want to consider. My new hospital is part of the clinical trial for one of the three treatments.)
Interestingly, according to the BioPharmaDive article, one of the people involved in one of the trials thinks the bispecifics might work even better as part of a combination (which is, of course, the direction that lots of new treatments are going in).
However, another person looking at the results was a lot less impressed after looking at the numbers.
Time will tell. Perhaps one or more of them will move on to a phase 2 trial, and we will see how things go.
For now, though, I'll take my new oncologist's excitement about them as a a good sign, and hope for the best.
Friday, December 7, 2018
Met the New Oncologist
I had my first appointment with the new oncologist today. It went well.
I won't go through all of my oncologist troubles again. If you want to read the whole sad tale, you're welcome to here.
My four previous oncologists all had offices in satellite centers, rather than the main cancer hospital. The new guy is at the main hospital.
Going to the main hospital was a new experience for me. I was there a few months ago for a special event on the first floor, but this was my first time really exploring the facility. I went up to one of the top floors, where the doctor's office was located, and checked in. The staff was friendly and efficient.
Outside of the waiting room, there was an outdoor garden. It's there to give patients a peaceful place to reflect and be with a little bit of nature.It was a little chilly to go out, but it was nice to know it was there.
After I was shown into the exam room, a nurse coordinator came in to talk to me. I'm considered a "first time patient" (even though I've been a patient in the larger hospital system for about 7 years), so the nurse coordinator gave me a brief orientation and some useful information in a folder.
It's a very different experience than going to one of the satellite offices. My First-timer Folder had a list of the people on my care team (the doc, the nurse coordinator, another nurse, a physician's assistant, and a social worker). If I need anything, there's one number that I can call for help. Kind of amazing.
My folder also had information about emotional issues for cancer patients, information about scans and blood tests, and a list of free services for patients at the cancer hospital (like art therapy classes and massage). I don't know if I was eligible for these things as a patient at the satellite hospital, but no one ever mentioned them.
So far, this was looking to be a good choice.
A few minutes after the nurse coordinator left, Dr. H came in with a nurse. He was great right from the start. He sat down and said,"So you had Dr K, and he retired. And the Dr. V. And then Dr. F, who told you he retired....Well, I'm not planning on going anywhere any time soon, so I think we'll be together for a long time."
And this was me:
I didn't ask him anything about his plans. He just volunteered it himself.
Now, when I meet a new oncologist (and I have more practice with this than I would like), I don't mention the blog, or the other writing, or that I'm a big Cancer Nerd who reads medical journals for fun. I just listen.
He told me a little bit about Follicular Lymphoma, and said there were some newer treatments available since I had Rituxan. He said he wanted me to do bloodwork after we met. [He also called me later in the day to tell me the blood results were back and everything was "phenomenal."]
He also told me he didn't think I needed a PET scan. "I'm not big on scans," he said, "not if there aren't any nodes popping up or any abnormalities in the blood work. If there's a reason, we'll do one, but otherwise we won't."
Me again:
(Extra points for you if you catch that "Hallelujah" reference.)
Dr. H also told me that if it came to it and I needed treatment again, he'd want me to get another biopsy to see what has changed over (almost) 11 years. And then we'd consider straight Rituxan again if it seemed appropriate.
It was my turn to ask questions, and I asked the same one that I asked Dr. V, the other lymphoma specialist I saw: what excites you about lymphoma research these days?
He told me he had been to ASH, and there weren't any real "miracle" presentations this year. Any progress was small but steady.
But what he did find exciting was, first, CAR-T. He thinks it looks great right now, and is doing some good work on patients with aggressive lymphoma. [Read more about CAR-T here.] He thinks that, in 5 years, CAR-T is going to be more widely available, and we'll understand it better then.
He also mentioned some new intratumoral immunotherapy treatments (I mentioned two of them in my last post). The treatment is injected into the tumor, and it "trains" the immune system to look for the cancer cells. He called it a kind of vaccine. I'm going to look into this some more and try to write about it soon.
Then he did a physical exam, and told me everything looked good.
And then it was over. I see him again in 6 months.
I like him. He answered questions before I asked them. His approach to the disease is in line with what I want (basically, leave me alone until we need to do something, and be available when we do).
I like the hospital, too. It's big and less convenient than the satellite offices, but....free massages, maybe.
All in all, a good visit. I'm happy with the choice I made.
I won't go through all of my oncologist troubles again. If you want to read the whole sad tale, you're welcome to here.
My four previous oncologists all had offices in satellite centers, rather than the main cancer hospital. The new guy is at the main hospital.
Going to the main hospital was a new experience for me. I was there a few months ago for a special event on the first floor, but this was my first time really exploring the facility. I went up to one of the top floors, where the doctor's office was located, and checked in. The staff was friendly and efficient.
Outside of the waiting room, there was an outdoor garden. It's there to give patients a peaceful place to reflect and be with a little bit of nature.It was a little chilly to go out, but it was nice to know it was there.
After I was shown into the exam room, a nurse coordinator came in to talk to me. I'm considered a "first time patient" (even though I've been a patient in the larger hospital system for about 7 years), so the nurse coordinator gave me a brief orientation and some useful information in a folder.
It's a very different experience than going to one of the satellite offices. My First-timer Folder had a list of the people on my care team (the doc, the nurse coordinator, another nurse, a physician's assistant, and a social worker). If I need anything, there's one number that I can call for help. Kind of amazing.
My folder also had information about emotional issues for cancer patients, information about scans and blood tests, and a list of free services for patients at the cancer hospital (like art therapy classes and massage). I don't know if I was eligible for these things as a patient at the satellite hospital, but no one ever mentioned them.
So far, this was looking to be a good choice.
A few minutes after the nurse coordinator left, Dr. H came in with a nurse. He was great right from the start. He sat down and said,"So you had Dr K, and he retired. And the Dr. V. And then Dr. F, who told you he retired....Well, I'm not planning on going anywhere any time soon, so I think we'll be together for a long time."
And this was me:
I didn't ask him anything about his plans. He just volunteered it himself.
Now, when I meet a new oncologist (and I have more practice with this than I would like), I don't mention the blog, or the other writing, or that I'm a big Cancer Nerd who reads medical journals for fun. I just listen.
He told me a little bit about Follicular Lymphoma, and said there were some newer treatments available since I had Rituxan. He said he wanted me to do bloodwork after we met. [He also called me later in the day to tell me the blood results were back and everything was "phenomenal."]
He also told me he didn't think I needed a PET scan. "I'm not big on scans," he said, "not if there aren't any nodes popping up or any abnormalities in the blood work. If there's a reason, we'll do one, but otherwise we won't."
Me again:
(Extra points for you if you catch that "Hallelujah" reference.)
Dr. H also told me that if it came to it and I needed treatment again, he'd want me to get another biopsy to see what has changed over (almost) 11 years. And then we'd consider straight Rituxan again if it seemed appropriate.
It was my turn to ask questions, and I asked the same one that I asked Dr. V, the other lymphoma specialist I saw: what excites you about lymphoma research these days?
He told me he had been to ASH, and there weren't any real "miracle" presentations this year. Any progress was small but steady.
But what he did find exciting was, first, CAR-T. He thinks it looks great right now, and is doing some good work on patients with aggressive lymphoma. [Read more about CAR-T here.] He thinks that, in 5 years, CAR-T is going to be more widely available, and we'll understand it better then.
He also mentioned some new intratumoral immunotherapy treatments (I mentioned two of them in my last post). The treatment is injected into the tumor, and it "trains" the immune system to look for the cancer cells. He called it a kind of vaccine. I'm going to look into this some more and try to write about it soon.
Then he did a physical exam, and told me everything looked good.
And then it was over. I see him again in 6 months.
I like him. He answered questions before I asked them. His approach to the disease is in line with what I want (basically, leave me alone until we need to do something, and be available when we do).
I like the hospital, too. It's big and less convenient than the satellite offices, but....free massages, maybe.
All in all, a good visit. I'm happy with the choice I made.
Tuesday, December 4, 2018
ASH: New Treatments (Without Rituxan)
Today is the last day of the ASH conference, and I've been too busy to fully enjoy everything that has been happening. I've barely been on Twitter lately, and that's where I get a lot of my ASH news. So I'm behind on reporting what's been happening there.
Before the ASH meeting begins, I get my information by looking at the abstracts to see what kind of Follicular Lymphoma research is being presented. Once the meeting starts, I get press releases and news stories about some of the more exciting presentations. Pharmaceutical companies and universities and hospitals like to brag about their good work. And I like to read it.
So I want to look at some of the good stuff that's been coming out of ASH, but maybe not in as much detail as usual. So here's a good excuse to do that -- a comment from reader Shelly from a couple of days ago:
Bob,
Are you finding any new info on "other" treatments that are showing PFS in patients that DON'T involve Rituxan??? Especially for relapsed.
Shelly
Thanks for the comment, Shelly. Yes, there are some other treatments that don't involve Rituxan. And some of them have been talked about at ASH this year.
Rituxan is kind of a miracle treatment. Overall Survival has increased for FL patients in the last 20 years or so, which is about how long Rituxan has been around. Rituxan seems to make other treatments better, which is why it's almost always included with things like CHOP or Bendamustine. And newer treatments are often tested in trials as part of combinations, very often with Rituxan as a part of the combo.
But some people have allergic reactions to it, and some have used it a few times and it no longer works for them. So Shelly's question about new treatments that don't involve Rituxan makes some sense.
Here are some that have been talked about at ASH this year:
A few important things to keep in mind:
First, I'm not a doctor. Talk to an oncologist about treatment options. But take all of this as reason for hope that we will have some good options in the future. (There are some really exciting things happening with immunotherapy.)
Second, remember that a lot of what happens at ASH and other oncology meetings involve treatments in clinical trials. That means they are still being developed and tested. They show promise, but they haven't been approved. It's not uncommon for something to do really well in a phase 2 trial and then not as well in a larger phase 3 trial when it gets tested on more patients. Be hopeful, but be realistic.
Finally, the only way for new treatments to be tested and then approved is if patients sign up for clinical trials. There are a decent number of options already approved for Follicular Lymphoma, but if you do need treatment, talk to your oncologist about clinical trial options, or get a second opinion from someone who knows about them. It may help you, and it will certainly help the rest of us.
*************
Once ASH is over, there will be lots of experts talking about what excited them most. I'll keep an eye out for those articles and videos, and pass along the good stuff.
Before the ASH meeting begins, I get my information by looking at the abstracts to see what kind of Follicular Lymphoma research is being presented. Once the meeting starts, I get press releases and news stories about some of the more exciting presentations. Pharmaceutical companies and universities and hospitals like to brag about their good work. And I like to read it.
So I want to look at some of the good stuff that's been coming out of ASH, but maybe not in as much detail as usual. So here's a good excuse to do that -- a comment from reader Shelly from a couple of days ago:
Bob,
Are you finding any new info on "other" treatments that are showing PFS in patients that DON'T involve Rituxan??? Especially for relapsed.
Shelly
Thanks for the comment, Shelly. Yes, there are some other treatments that don't involve Rituxan. And some of them have been talked about at ASH this year.
Rituxan is kind of a miracle treatment. Overall Survival has increased for FL patients in the last 20 years or so, which is about how long Rituxan has been around. Rituxan seems to make other treatments better, which is why it's almost always included with things like CHOP or Bendamustine. And newer treatments are often tested in trials as part of combinations, very often with Rituxan as a part of the combo.
But some people have allergic reactions to it, and some have used it a few times and it no longer works for them. So Shelly's question about new treatments that don't involve Rituxan makes some sense.
Here are some that have been talked about at ASH this year:
- In a phase 2 clinical trial, a treatment called G100 showed some success when combined with another called Pembrolizumab for relapsed/refractory patients. G100 is an immunotherapy that works on cancer cells to make them more receptive to the immune system. The G100 is injected into the tumor, where it reaches the cancer cells. Pembrolizumab is also known as Keytruda. It goers after the PD-1 receptor on lymphoma cells, and turns of the signal that keeps the cell from dying. In this trial, the combo had a PFS of just under a year (so far). the combo had an Overall Response Rate of 46%, and kept the disease under control for 92% of patients.
- In a phase 1 trial, a treatment called Mosunetuzumab showed a lot of promise. Mosunetuzumab is another immunotherapy -- it activates an immune cell called a T cell to go after the B cells that are causing the lymphoma. In patients with relapsed/refractory FL, the Response rate was 69%, with a 38% Complete Response. This is a phase 1 trial, so it was fairly small, but the treatment does get people excited.
- Another treatment, REGN1979, also showed lots of promise. Like Mosunetuzumab, REGN1979 is bispecific, meaning it can attach itself to two different targets, a T cell and a B cell. REGN1979 was tested in a very small phase 1 study of just 10 relapsed/refractory FL patients, all of them showed a response, with 8 of the 10 showing a Complete Response. The news was good enough to have the developers want to move on to a larger phase 2 trial.
A few important things to keep in mind:
First, I'm not a doctor. Talk to an oncologist about treatment options. But take all of this as reason for hope that we will have some good options in the future. (There are some really exciting things happening with immunotherapy.)
Second, remember that a lot of what happens at ASH and other oncology meetings involve treatments in clinical trials. That means they are still being developed and tested. They show promise, but they haven't been approved. It's not uncommon for something to do really well in a phase 2 trial and then not as well in a larger phase 3 trial when it gets tested on more patients. Be hopeful, but be realistic.
Finally, the only way for new treatments to be tested and then approved is if patients sign up for clinical trials. There are a decent number of options already approved for Follicular Lymphoma, but if you do need treatment, talk to your oncologist about clinical trial options, or get a second opinion from someone who knows about them. It may help you, and it will certainly help the rest of us.
*************
Once ASH is over, there will be lots of experts talking about what excited them most. I'll keep an eye out for those articles and videos, and pass along the good stuff.
Thursday, November 29, 2018
Rituxan Biosimilar Approved
The FDA has approved a Rituxan biosimilar, called CT-P10 or Truxima. The approval is for some B Cell Lymphomas, including Follicular Lymphoma.
It's a potentially big deal.
A biosimilar is kind of like a generic drug. Generics are a little easier to make. A drug is a chemical compound, so once you figure of the chemistry, you have a recipe to follow. A biosimilar is harder, because it's not a chemical compound, but a biological agent -- something that comes from a living thing. Copying it is a lot harder.
Think of it this way -- making a generic drug is like following the recipe to make a cake. Making a biosimilar is like trying to figure out how to get the eggs when you don't have any chickens -- just an egg that you need to make a copy of.
Finding a Rituxan biosimilar has been a goal for a while, because Rituxan has been such an important part of most B Cell Lymphoma treatments for the last 20 years or so. When a treatment is approved, the company that developed it is given a period of time when they have exclusive rights to that treatment. But after a period of time, others are allowed to try to make copies (biosimilars, in Rituxan's case) and try to get the, approved.
The FDA was satisfied that Truxima will do the same job, with the same side effects, as Rituxan.
The reason this is a big deal for patients is that, like generic drugs, a biosimilar should lower the cost of treatment. When Rituxan was first created, it cost a lot of money to do the research and then to market the treatment. That exclusive period of time gave the company time to make up all those costs.
A biosimilar (or a generic) doesn't need to make up those research costs (it's already been developed), or the marketing costs (everyone knows how great Rituxan is). So they should be able to sell the treatment at a lower cost.
It will be interesting to see how popular it becomes. Insurance companies may like it, since it should lower costs. But will oncologists trust it? Old habits die hard, and they may just keep going with what they are used to.
Interestingly, just a few weeks ago, another company that is developing a Rituxan biosimilar decided not to go any further with it in the U.S. The FDA had asked for additional data in the spring before giving their approval, and the company decided that another biosimilar (probably Truxima) would be approved before they could get the FDA what it wanted.
I'll be watching closely for any reports of Truxima's use. If anyone out there is offered it during treatment, I'd love to hear how it goes.
It's a potentially big deal.
A biosimilar is kind of like a generic drug. Generics are a little easier to make. A drug is a chemical compound, so once you figure of the chemistry, you have a recipe to follow. A biosimilar is harder, because it's not a chemical compound, but a biological agent -- something that comes from a living thing. Copying it is a lot harder.
Think of it this way -- making a generic drug is like following the recipe to make a cake. Making a biosimilar is like trying to figure out how to get the eggs when you don't have any chickens -- just an egg that you need to make a copy of.
Finding a Rituxan biosimilar has been a goal for a while, because Rituxan has been such an important part of most B Cell Lymphoma treatments for the last 20 years or so. When a treatment is approved, the company that developed it is given a period of time when they have exclusive rights to that treatment. But after a period of time, others are allowed to try to make copies (biosimilars, in Rituxan's case) and try to get the, approved.
The FDA was satisfied that Truxima will do the same job, with the same side effects, as Rituxan.
The reason this is a big deal for patients is that, like generic drugs, a biosimilar should lower the cost of treatment. When Rituxan was first created, it cost a lot of money to do the research and then to market the treatment. That exclusive period of time gave the company time to make up all those costs.
A biosimilar (or a generic) doesn't need to make up those research costs (it's already been developed), or the marketing costs (everyone knows how great Rituxan is). So they should be able to sell the treatment at a lower cost.
It will be interesting to see how popular it becomes. Insurance companies may like it, since it should lower costs. But will oncologists trust it? Old habits die hard, and they may just keep going with what they are used to.
Interestingly, just a few weeks ago, another company that is developing a Rituxan biosimilar decided not to go any further with it in the U.S. The FDA had asked for additional data in the spring before giving their approval, and the company decided that another biosimilar (probably Truxima) would be approved before they could get the FDA what it wanted.
I'll be watching closely for any reports of Truxima's use. If anyone out there is offered it during treatment, I'd love to hear how it goes.
Sunday, November 25, 2018
ASH: Bendamustine and Transformation
Another ASH preview.
But first, I want to alert you Cancer Nerds to The Leonard List. Lymphoma researcher Dr. Jon Leonard has been creating the Leonard List for the past few years. He lists what he thinks are the 10 most significant or interesting lymphoma-related abstracts from ASH. He posts them one a day on Twitter in the days leading up to ASH. But this year he also discussed them in a podcast, which you can listen to here. (He added 5 more to the podcast, so you get a nice bonus there.)
So, basically, he does what I do, except more of them, and a broader look at lymphoma and not just FL, and he's an actual expert, unlike me. But otherwise, the same thing. (I really enjoy Dr. Leonard's stuff on Twitter. He gives his followers lots to think about.)
The Leonard List includes a few ASH abstracts that focus on Follicular Lymphoma research, or issues related to FL, including this one: "Frontline Therapy with Bendamustine and Rituximab (BR) in Follicular Lymphoma: Prognosis Among Patients with Progression of Disease By 24 Months (POD24) Is Poor with Majority Having Transformed Lymphoma."
The study was conducted by researchers in British Columbia, Canada, where Bendamustine + Rituxan is the standard treatment now for patients with symptomatic, advanced FL. Before that, the standard treatment for these patients was R-CVP. The researchers wanted to see if B-R has been more effective than R-CVP.
And the short answer is that, yes, it has been more effective, which is what they expected. With a median follow-up of just under 3 years, they found that the 2 year Event Free Survival for the 296 patients receiving B-R was 85%, and the Overall Survival was 92%. Looking back at 347 R-CVP patients, the EFS was 76%, though the OS was the same. So B-R was better in keeping patients from having problems, but not in keeping them alive any longer.
The more interesting information came when they looked at patients that had transformed to an aggressive lymphoma.
In the B-R group 28 patients (about 9%) transformed from FL to an aggressive lymphoma. The 2 year OS for this group was only 39%.
They also looked at POD24, or Progression of Disease within 24 months after treatment with immunochemotherapy. This is sometimes called EFS24, or Event Free Survival within 24 months of immunochemo. Same basic concept. These patients generally have a worse outcome than other FL patients whose disease does not return within 24 months. In the B-R group, POD24 occurred in 35 patients (about 12%). That's a little lower than the 20% of patients found in some other studied. However, those 35 included 27 of the patients who had transformed. Overall, the 2 year OS for POD24 patients was 38%.
Compare that to the R-CVP group. In that group there were 77 POD24 patients -- about 22%, with 31 of those 77 patients having transformed.
So what does all of this mean? Well, first of all, it confirms that FL patients whose disease does not progress within 24 months generally have a very good long-term prognosis. But it also confirms that patients who do progress have a poor prognosis. For patients taking B-R, the rate of transformation is about the same as with other treatments like R-CVP. However, the incidence of POD24 is lower -- Bendamustine might keep patients from having their disease return so quickly.
You can see that when you compare the POD24 numbers of the two treatments -- most of the POD24 patients for B-R also transformed. Transformation and POD24 are not always the same thing. So patients who have had POD24 happen haven't necessarily transformed.
The implication there is that B-R seems to do a good job of keeping advanced, asymptomatic FL from returning quickly. And for those that do have their FL return (as opposed to those who have transformed to something other than FL), "novel approahces specific to FL" might be used, instead of more aggressive treatments that are meant for transformed FL.
So while this probably isn't a "blockbuster," it does seem to give us some important information about that POD24/EFS24 population, and how it is (and is not) related to transformation. Plus, it made the Leonard List, so you know it's a good one.
More ASH stuff to come.
But first, I want to alert you Cancer Nerds to The Leonard List. Lymphoma researcher Dr. Jon Leonard has been creating the Leonard List for the past few years. He lists what he thinks are the 10 most significant or interesting lymphoma-related abstracts from ASH. He posts them one a day on Twitter in the days leading up to ASH. But this year he also discussed them in a podcast, which you can listen to here. (He added 5 more to the podcast, so you get a nice bonus there.)
So, basically, he does what I do, except more of them, and a broader look at lymphoma and not just FL, and he's an actual expert, unlike me. But otherwise, the same thing. (I really enjoy Dr. Leonard's stuff on Twitter. He gives his followers lots to think about.)
The Leonard List includes a few ASH abstracts that focus on Follicular Lymphoma research, or issues related to FL, including this one: "Frontline Therapy with Bendamustine and Rituximab (BR) in Follicular Lymphoma: Prognosis Among Patients with Progression of Disease By 24 Months (POD24) Is Poor with Majority Having Transformed Lymphoma."
The study was conducted by researchers in British Columbia, Canada, where Bendamustine + Rituxan is the standard treatment now for patients with symptomatic, advanced FL. Before that, the standard treatment for these patients was R-CVP. The researchers wanted to see if B-R has been more effective than R-CVP.
And the short answer is that, yes, it has been more effective, which is what they expected. With a median follow-up of just under 3 years, they found that the 2 year Event Free Survival for the 296 patients receiving B-R was 85%, and the Overall Survival was 92%. Looking back at 347 R-CVP patients, the EFS was 76%, though the OS was the same. So B-R was better in keeping patients from having problems, but not in keeping them alive any longer.
The more interesting information came when they looked at patients that had transformed to an aggressive lymphoma.
In the B-R group 28 patients (about 9%) transformed from FL to an aggressive lymphoma. The 2 year OS for this group was only 39%.
They also looked at POD24, or Progression of Disease within 24 months after treatment with immunochemotherapy. This is sometimes called EFS24, or Event Free Survival within 24 months of immunochemo. Same basic concept. These patients generally have a worse outcome than other FL patients whose disease does not return within 24 months. In the B-R group, POD24 occurred in 35 patients (about 12%). That's a little lower than the 20% of patients found in some other studied. However, those 35 included 27 of the patients who had transformed. Overall, the 2 year OS for POD24 patients was 38%.
Compare that to the R-CVP group. In that group there were 77 POD24 patients -- about 22%, with 31 of those 77 patients having transformed.
So what does all of this mean? Well, first of all, it confirms that FL patients whose disease does not progress within 24 months generally have a very good long-term prognosis. But it also confirms that patients who do progress have a poor prognosis. For patients taking B-R, the rate of transformation is about the same as with other treatments like R-CVP. However, the incidence of POD24 is lower -- Bendamustine might keep patients from having their disease return so quickly.
You can see that when you compare the POD24 numbers of the two treatments -- most of the POD24 patients for B-R also transformed. Transformation and POD24 are not always the same thing. So patients who have had POD24 happen haven't necessarily transformed.
The implication there is that B-R seems to do a good job of keeping advanced, asymptomatic FL from returning quickly. And for those that do have their FL return (as opposed to those who have transformed to something other than FL), "novel approahces specific to FL" might be used, instead of more aggressive treatments that are meant for transformed FL.
So while this probably isn't a "blockbuster," it does seem to give us some important information about that POD24/EFS24 population, and how it is (and is not) related to transformation. Plus, it made the Leonard List, so you know it's a good one.
More ASH stuff to come.
Subscribe to:
Posts (Atom)