Saturday, February 25, 2017

Rituxan Biosimilar Approval

A biosimilar for Rituxan has been approved for use in Europe. It is called Truxima, and will be available in the UK, Germany, Italy, Netherlands, Belgium, Republic of Ireland and Luxembourg.

Some background: Cancer treatments cost money to develop. When they fail, the company that develops them loses money. So be it -- it's the risk those companies take. But when they are successful, they can make billions of dollars for the business. Rituxan (also known as Mabthera is other parts of the world) is one of those successes.

The company that creates a successful treatment gets exclusive rights to that treatment for a set number of years. In a sense, this a reward for their taking the risk to do the research and testing that goes into a successful treatment.

But that reward doesn't last forever. After that set period, other companies are allowed to create "biosimilars" -- copies of the treatments that work in the same way (and, after some testing, with the same results).

A biosimilar isn't the exact same thing as the original. That's right in the name -- it is "similar" to it. The company that makes the biosimilar also has to invest in production. They have to figure out what the original treatment was, and test whether or not it will work. But they don 't have to spend money on marketing the treatment, the way the original maker had to. The biosimilar is coming into a situation where people already know that it works.

And so for that reason, biosimilars are (or should be) less expensive than the original. A lot of the cost of the treatment has already been paid. The hope is that Truxima will save patients and healthcare systems lots of money because it will be sold cheaper than Rituxan/Mabthera.

There is a chance that doctors will not prescribe the biosimilar, and will stick to the original, for whatever reason. And there is a chance that, for some patients, the biosimilar will be just different enough from the original that it  won't work as well. (My wife takes a medication that just won't work in the non-original form.)

But overall, I think biosimilars are a good thing. The biosimilar version of Rituxan will likely be in the news sometime this year. I'll keep an eye out.

Tuesday, February 21, 2017

Hepatitis C Treatment Works for Follicular Lymphoma?

A reader named Ilia posted a comment yesterday about a possible treatment for Follicular Lymphoma:

I would like to get your opinion on something more exciting than watching and waiting - how about a complete remission of FL following anti- viral therapy for Hepatitis C. It was published in New England Journal of Medicine in October and would not drawn my special attention except one of the authors is Adreshna.

I hadn't heard of this article, so I thought it was worth looking into, and writing about.

But this is also a good time to remind everyone of something. When I'm asked for my opinion on something related to Follicular Lymphoma, I think it's important to remind everyone that I am not an oncologist, or a medical doctor of any kind. I'm not a biologist, or scientist, or researcher. I like to call myself a Cancer Nerd. I'm someone who has an interest in cancer, especially Follicular Lymphoma, and I have enough of a background in science to be able to understand medical journal articles and comment on them. So my opinion is only worth so much. If I'm "giving my two cents," as the saying goes, there are plenty of experts whose opinion on FL is worth two dollars, or pounds, or euros, or whatever.

So as long as we're straight on that, let's get to Ilia's comment.

The piece did indeed appear in the prestigious New England Journal of Medicine last October. It's called "Remission of Follicular Lymphoma after Treatment for Hepatitis C Virus Infection."
But there's an important distinction between this study and many others that appear in medical journals. Most of the articles that I comment on are peer-reviewed studies. That means they report on clinical trials or other research, and before it gets published in the journal, it is approved by some other experts in the field. They make sure that the trial was set up properly, and the results and conclusions are really what the authors say they are. Peer-reviewed articles are the gold standard -- you can trust what they say.

On the other hand, the article on Hepatitis C treatments is labeled "Correspondence" -- a letter to the editors. Most of the time, correspondence is a comment on an article that the journal published, though sometimes the letter might describe an interesting medical situation. It's a way of getting other doctors or researchers interested in exploring the subject further.

In this particular letter, the authors are doing just that -- just describing an interesting situation. As the title implies, the interesting situation is that a patient who had both Follicular Lymphoma and Hepatitis C. The patient was given treatment for the Hepatitis, and it put the Lymphoma into remission.

The important thing about this (and maybe why there wasn't a bigger deal made of it) is that the letter describes ONE patient. Clinical trials that result in a treatment being approved will often involve hundred of patients. That's the only way to make sure that the treatment will work on a large number of patients. ONE patient won't prove anything -- but it might get enough people interested to explore it more.

And that's just what happened here. There is a clinical trial in the U.S. that is looking into the Hepatitis C treatments Sofosbuvir and Ribavirin, and whether or not they will help with Follicular Lymphoma and other indolent lymphomas. The two treatments are anti-viral agents -- in different ways, they mess with the viruses that cause Hepatitis C. Ribavirin, for example, messes with RNA , which is necessary for DNA to copy itself, and thus for a virus to copy itself. I don't know the exact way that it works with lymphoma, but it makes sense that it messes with cancer cells trying to copy themselves.

So that's where we are with this potential treatment. It's an early trial -- only 21 patients are being recruited, and it will be at least a year before any results are in.

So Ilia, here's my opinion -- it looks promising enough for a trial. Not all trials are successful -- if they were, we'd have a whole lot more treatments than we do.

But that doesn't mean I'm not hopeful about it.

Thanks for making me aware of. I'll be sure to keep an eye on possible results when they come in.

Thursday, February 16, 2017

Appointment with a New Oncologist

I had an appointment today with a new oncologist. I think I'm going to keep him.😀

First, let me say that my check-up went well. It was the usual -- blood work, a physical exam, and my reporting on how I am feeling. Everything looks great. Blood is normal, I feel fine, and he didn't feel anything weird. I'm good for another 6 months.

Now, a little history, since the focus here is on finding a new oncologist. My first oncologist was Dr. R. I saw him for 8 years, starting on the day after I was diagnosed. I loved Dr. R. He was young, he was well-informed, and he was friendly. I actually looked forward to going to the oncologist. But then he broke my heart and moved to warmer climates, taking a job at a medical school. I miss him. But he seems happy.

After Dr. R, the practice assigned me to Dr. K. I did not like Dr. K very much. He was nice, but he didn't listen, and that was the biggest problem. He seemed to have a rehearsed speech for my visit, and if I tried to tell him I knew about things he was telling me (basic things like what a PET scan was, or the 3 different types of blood cells), he didn't notice or care and just kept talking. During my last visit, he insisted that I get a PET scan. I asked why, and he told me that he didn't think he would find anything on the scan, but he wanted me to get one anyway. I'm a relatively young man with a few scans already under my belt, and I don't think a scan is useful for me at this point, and could actually do more harm than good. But he insisted. At that point, I decided it was time for a new oncologist.

Interestingly, I got a letter from the practice that Dr. K had retired in December, and I would need to find a new oncologist anyway. That might explain some things. He really seemed like someone who had lost interest in the job. As I said, he was a nice guy, and probably had some patients who liked him a lot. But he just wasn't what I needed.

So a month ago, I got a call from the practice. They wanted me to schedule an appointment with Dr. V. The practice I go to is one of about 10 satellite practices for a large teaching and research hospital, attached to a medical school. Most of the oncologists at the satellite practices are clinical oncologists -- their job is to see patients. At the main research hospital, the oncologists see patients, but also do research, conduct clinical trials, and teach at the medical school. Dr. V is one of those oncologists. He works at the main research hospital, and would come to the satellite campus one day a week to see patients.

So I said Yes to an appointment with Dr. V. And I'm glad I did.

Before I describe the appointment, let me say that I know that I am lucky to be able to choose  my own oncologist. I know there are lots of cancer patients who can't choose. Maybe they live an an area with only one oncologist nearby. Or maybe their health care plan doesn't give them a choice. I'm sorry that's the case for people, and I wish it was different. I'm lucky to be in a situation where I can choose my oncologist, at least to some extent.

My visit with Dr. V opened with a review of my current medications. We made some small talk as he looked up my record on the computer (he's a fan of jazz music, and I conveniently have a son who is a jazz musician). As he looked at my medications, he asked why I was taking vitamin B-12. I told him that I had been taking another medication that was causing B-12 problems, but that I had taken myself off of that medication because I was reading about too many side effects. "Well, then maybe it's time to stop taking B-12, too, huh?"

That's a small but important comment. One of the things I liked about Dr. R was his "Do no harm" philosophy -- if there wasn't a good reason for a treatment, or a scan, or some other intervention, then we wouldn't do it. It's what led to my watching and waiting for two years instead of starting on treatment right away. I liked that Dr. V seemed to be taking the same approach.

As we went through my history, that was reinforced. He said he probably wouldn't have given me Rituxan at two years. I explained that I had the Rituxan because of some swelling in my leg, and he agreed that it was a good idea (the notes he had from Dr. K were not very detailed). But that was another example of the n"Do no harm" approach that I liked.

Another example came a few minutes later, when we were discussing my next appointment. He saw that I was getting an appointment every 4 to 6 months. He said, "I really think you could probably stretch this out to a year. We can do 6 months if you'd rather not wait that long, but a year would probably be fine." I said I'd rather do 6 months, which he said was OK. He continued: "I see that Dr. K ordered a PET scan. I'd like to cancel that." I said, enthusiastically, that I was fine with cancelling it. He went on: "We don't do scans like that anymore. Older doctors still believe in surveillance scans, but younger doctors have been trained differently. We worry about too much radiation leading to secondary cancers 20 years from now."

So I was happy about that. He reminded me a lot of Dr. R -- young, friendly, and informed, with a philosophy that matched my own. I was happy that I say him.

But what really clinched it for me was what happened next. We were finishing up, and he asked if I had any final questions. I said, "Yes, just one. As a hematologist, is there anything that excites you about lymphoma treatments these days?"

His eyes got wide, and he said, "LOTS!" 

And then he talked to me for 15 minutes straight about what excited him about lymphoma. It was glorious. He didn't dumb it down. But he explained it well. And I did my best to let him know that I understood and was interested.

He told me that he started out as a leukemia specialist, but he switched to lymphoma because he liked his boss so much. But he was glad that he did, because advances in treating leukemia have kind of stalled, but there are lots of interesting advancements happening in lymphoma.

He went through some of the stuff happening in aggressive lymphomas. The goal with all lymphomas is to move away from traditional chemotherapy, though that's hard to do with aggressive types, which do seem to benefit from chemo. But he did say that there were some exciting trials with Immunotherapies that were resulting in 80% response rates with 20-30% Complete Responses. Then he talked about other indolent lymphomas, like CLL and Mantel Cell, that had some exciting new treatments, like Ibrutinib.

And then he got to Follicular Lymphoma. He said FL was "complicated." The goal, as with other lymphomas, is to move away from traditional chemotherapy. There were lots of treatments out there being tested in trials, with different levels of success. He mentioned Idelalisib, which he was very excited about, but which also showed some severe side effects, leading to some trials being shut down. He was involved with one of those trials, and was unhappy about it, because he thinks Idelalisib shows some promise for Follicular Lymphoma.

He talked about another FL trial he is working with right now. The treatment is called G100, and as he described it, it is a vaccine that is injected into affected lymph nodes in one site of the body. The hope is that the vaccine will train the immune system, and it will then travel to affected nodes in other parts of the body. (I confess that I don't know much about this treatment. It's in phase I/II trials, so maybe it's too early to show any strong results. But I'll definitely keep an eye on it.)

And then he ended by saying that what he really loved about being an oncologist is that he can cure people. He has colleagues who are cardiologists. When someone has heart damage, they can help them, but they can't cure them. But an oncologist can. After my appointment, he was going to see someone who had been in remission for about 10 years. "I look at the scan from when he was diagnosed, and the scan from a month ago....the difference between's like we're performing magic...."

You know how I sometimes post videos of lymphoma researchers who talk about treatments with so much excitement? I had one right in front of me. It was so cool.

That's what I need. And that's what I found.

It was a good visit.

Sunday, February 12, 2017


A couple of items related to CAR-T that are a little bit older, but worth looking at:

First, the online magazine CureToday has an article on CAR-T, specifically the ZUMA-1 trial that was reported on at the ASH conference in December, and in the journal Blood.

The article described the results from the ZUMA-1 trial, which looked at CAR-T in patients with aggressive lymphomas, mostly Diffuse Large B Cell Lymphoma (which is why I didn't write about it earlier), but also transformed Follicular Lymphoma (which is why I'm becoming aware of it now). I'll let you read the articles yourself, but basically, the patients were given a CAR-T treatment called KTE-C19, which targets lymphoma cells that have the CD19 protein on their surface. With a CAR-T treatment, the patient's T-cells (a kind of immune cell) are removed from the body, changed so that they recognize the cells with CD19, and then put back into the patient's body, where they hunt down the bad guys.( updated their section on CAR-T about a week ago; you can find some nice links there to find out more about the treatment.)

For cohort 1, the DLBCL patients, the results were excellent -- about 76% of patients (51 patients overall) had a response. Just as  importantly, the "manufacturing" process was successful, with 99% of patients being able to get their T cells changed and put back into their bodies. The average time for patients to receive their changes T cells was about 17 days, which is important because they were not all st the same site. And the CAR-T cells expanded within 14 days to the point where there were enough of them floating around to be able to do their job, the way naturally-occurring T cells do. So, lots of successes.

Cohort 2 included the transformed Follicular Lymphoma patients, and was much smaller -- 6 patients total, 3 of them with transformed FL. But the results were just as good. All 6 patients had a Complete Response, and all were still in complete remission after a median of 3 months of follow-up.

Now, 3 patients measured over 3 months is enough to give us some hope, but certainly not enough to make us think we have The Answer. This trial will continue, and I'm sure we all look forward to long-term results with a larger population.

Which brings me to another article: "Immunotherapy Cancer ‘Cure’ Headlines Distract from Fascinating Science." This was posted in the comments about a week ago by a reader named Popplepot (great name!) and it's worth revisiting. It was published about a year ago in the Science Blog published by the organization Cancer Research UK, soon after the first results from a CAR-T trial. The results were fantastic, and some of the experts commenting on it said things like "CAR-T might lead to a cure some day." Media reports heard the word "cure" and that became the focus, leaving out that the experts said "might" and "some day." The article reminds us of what makes CAR-T so fascinating (and it really is fascinating, given that it overcomes the basic problem with cancer -- why doesn't the body recognize cancer cells as invaders?).

But the Cancer Research UK article also makes us aware of some of the problems with early CAR-T trials -- they are small, and they also point to some nasty side effects (which resulted in a couple of deaths of patients).

So it's a good reminder for all of us to pay attention to some of the problems that come with new treatments. I know I'm guilty of this. I'm naturally upbeat and positive, so I ignore some of the negatives that come with reports of new treatments and clinical trial results. I'm working on it.

We're going to see more and more CAR-T results, I'm sure. Which reminds me of another reader's recent comments. William May, whose wife has had great success with CAR-T, was expecting the recent OncLive Peer Exchange video series to address CAR-T. It looks like they've moved on from Follicular Lymphoma treatments to CLL treatments, and no mention of CAR-T. I share your disappointment, William.

But that's OK. As I said, there will be plenty of stuff to read about CAR-T in the months and years to come. Looking forward to it.

(And thanks, Popplepot and William, for you comments.)

Tuesday, February 7, 2017

Long-Term Follow-Up of FL Patients

The Fred Hutchinson Cancer Research Center in Seattle, Washington is one of those top-notch lymphoma places that I hope you never need to use.

Their news service posted a great piece a couple of weeks ago called "How Cancer Survivors are Teaching Researchers — Even Decades Later," and it discusses some long-term (very long-term) research that they do on cancer survivors. They have something called the Long-Term Follow Up Program that keeps up with patients after a Stem Cell Transplant or Bone Marrow Transplant -- some patients have been followed for over 40 years. Of course, that gives researchers an awful lot of information about cancer survivors. They learn about emotional as well as physical things.

But Fred Hutch isn't only interested in transplant survivors. As the article also discusses (and what is no doubt more interesting for us), researchers at the Center have also been engaged in a long-term study of Follicular Lymphoma patients. The study started in 2001, and involved advanced FL patients who hadn't been treated before. 500 patients were given either R-CHOP or CHOP + RadioImmunoTherapy. The first results of the trial were published in 2013, and found that both groups did really well -- over 90% were still alive after 5 years.

Long-term follow-up is especially important for Follicular Lymphoma patients, because our disease is so slow-growing. The R-CHOP vs CHOP + RIT trial had excellent long-term results as well. Over 80% of patients are still alive. There is no difference in Overall Survival between the two groups, though Progression-Free Survival was a little better for the RIT group.

But the big picture here is all of the information that the study provides. So many studies focus on relatively short-term results that it's hard to know if there really is a benefit. If a treatment cures one cancer but gives you another one 10 years later, is that really a success? Long-term follow-up helps answer that question, and provides more detail about other issues, physical and emotional, than can help doctors and patients make decisions about treatments.

And again, when we have a disease with an Overall Survival that gets close to 20 years for a lot of us, then that kind of information matters. Quality of Life matters for us. Treatments need to help us now, but not hurt us later.

There's a little more to the article -- some stories of individual patients. It's a nice piece, and a nice reminder of a couple of things: 1) as patients, we need to think about the many years we may have left, and 2) long-term clinical trials can help us out a lot, but people need to volunteer for them if they're going to work.

Thursday, February 2, 2017

Abexinostat in Europe

A Phase 2 clinical trial for Abexinostat showed some good results for Follicular Lymphoma.

Haematologica: The Journal of the European Hematology Association published in article in their January edition called "Safety and Efficacy of Abexinostat, a Pan-Histone Deacetylase Inhibitor, in Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Results of a Phase 2 Study."

Abexinostat, as the title says, is a Pan-Histone Deacetylase Inhibitor. There are lots of different types of inhibitors being tested (and approved) for lots of different types of cancer these days, and in general, they work by stopping (or inhibiting) some function that a cancer cell needs in order to survive. Histone Deacetylase Inhibitors have actually been around for a while. They can help patients with epilepsy control seizures, and can help as mood stabilizers. There is also some research going on that shows they might help patients with Alzheimer's and other diseases where the nerves degenerate.

They do this by inhibiting Histone Deacetylase. This is all part of a very cool process that helps the body coil and uncoil DNA so cells can make copies of themselves. Histone Deacetylase helps remove something called an acetylase, whuch sets off a complex chain of reactions. Histone Deacetylase Inhibitors help to keep this from happening, meaning the cancer cells can't make copies of themselves.

(If you want to see a video of how Abexinostat works, you can watch one here. It refers to Abexinostat's old name, PCI-247812. The video was posted by someone named "Food Cheese," which made me think twice about linking to it. But then I remembered that I go by the name "Lympho Bob," and I really shouldn't judge people just because they post online with a stupid name.)

Anyway, the European trial involved patients with several different types of lymphoma, including Follicular Lymphoma. Patients were relapsed or refractory to treatment -- something wasn't working anymore. There were a total of 87 patients who made it to the evaluation point of the trial. While only 28% of them had a response (and only 5% had a complete response), the numbers for the small group of FL patients were the best of the bunch, with 56% having a response. The researchers believe more research is necessary for some of the groups that showed success, including FL, especially with a less-intense dosing schedule (which seemed to cause some side effects that could be avoided or lessened).

A trial with a less-intense dose actually took place in the U.S., and was reported on last spring. Like this European trial, the U.S. trial looked at patients with different types of lymphoma, and found that Follicular Lymphoma patients fared best (a 64% Overall Response Rate). Those researchers also called for more studies.

So maybe Abexinostat will show us something in a few years. It doesn't seem to be a knockout treatment on its own, but it could end up in a combination that kicks some cancer butt.