Sunday, February 28, 2016

New Treatent Approved for Follicular Lymphoma

The FDA announced on Friday that it has approved Obinutuzumab (also known as Gazyva) as a treatment for Follicular Lymphoma. This is good news.

Obinutuzumab is a humanized monoclonal antibody that targets CD20. So it's a lot like Rituxan, which also targets CD20. The big difference is that Obinutuzumab is humanized -- made from human cells, not mouse cells, like Rituxan. There is some feeling that this will make it safer than Rituxan and will cause fewer allergic reactions.

The specific treatment that was approved involves Obinutuzumab + Bendamustine, followed by Obinutuzumab on its own. It is meant for patients who took Rituxan + chemotherapy, but who have had the disease return within 6 months.

The approval was based on the GADOLIN study, which involved 321 FL patients (along woth some other NHLs), which compared the Obinutuzumab + Bendamustine + Obinutuzumab, to Bendamustine on its own. Patients who were given only Bendamustine had a median Progression Free Survival (the time it took for the FL to come back) of 13.8 months. The Obinutuzumab patients had a median PFS of 29.2 months -- more than a year, and more than double the Bendamustine results.

Those are good results.

It will be interesting to see if Obinutuzumab gets a lot of off-label use as a single-agent treatment, given that it is similar to Rituxan. But it's more likely that it will be used in combination treatments, the way Rituxan is used so often. there are already a bunch of trials for Obinutuzumab combinations.

So we have another arrow in the quiver. Cause for celebration.

Thursday, February 25, 2016

Follicular Lymphoma: Future Strategies

New video from OncLive, posted a few days ago:

Dr. Richard Furman of weill Cornell and Dr. Bruce Cheson of Georgetown University discuss where we might be headed in treating Follicular Lymphoma.

Dr. Furman points out that Idelalisib seems to work better in CLL than in Follicular Lymphoma, so perhaps using it in combination will improve results. He mentions combining it with Rituxan and Bendamustine, which is getting good clinical trial results, though the combination also has some unpleasant side effects.

Dr. Furman also discusses Lenalidomide/Revlimid + Rituxan (R-squared). Like other combinations, this one improves the performance of the two individual treatments, and makes them last longer.

Dr. Cheson (you know I'm fond of him) discuss Ibrutinib, and the results that we are just seeing in Follicular Lymphoma. Ibrutinib is also being combined for better results. He mentioned combinations with Bendamustine, with R-squared, with anti-CD20 antibodies (like Rituxan, probably, and I'm not sure what else. Maybe Ofatumumab? Obinutuzumab? Ocaratuzumab?).

Dr. Cheson also points out that newer treatments like these two are expensive, and we really need biomarkers to use them most effectively -- something that can be tested so we know if a certain treatment is likely to work. Knowing which patients will benefit most from the treatments will make them all the more effective (and cost-effective).

Finally, Dr. Cheson points out that we are coming to the end of traditional chemotherapy, which kills lots of healthy cells as it kills cancer cells. Instead, we will see targeted agents like R-squared. We can envision targeting Follicular Lymphoma:

First, by targeting the surface of the cell with treatments like Rituxan, which finds a protein on the surface of the cell.
Second, by targeting pathways within the cell, with inhibitors that keep the cell from performing certain tasks that it needs to perform in order to survive. Idelalisib is an example of an inhibitor.
Finally, by targeting the microenvironment -- the area that surrounds the cell, where things happen that are necessary for the cell to survive. Lenalidomide is an example.

And here's the bombshell -- Dr. Cheson thinks that, if we find the right combination of treatments, we can eventually find a cure without needing chemotherapy. (Now do you see why I'm fond of him?)

Of course, we don't have a cure now, and won't (probably) in the near future. Maybe some of the treatments we have  now will be part of the cure, but maybe we haven't discovered them yet, and the ones we have now are just helping us figure out what works and how to make it better.

And of course, we do still have chemo, and it does have a place in our menu of options. But if you believe Dr. Cheson, it is on its way out, and our future is in the kind of combinations that he and Dr. Furman describe here.

Monday, February 22, 2016

CAR-T in the News

There has been a lot of enthusiasm in the news for CAR-T treatments for blood cancers, based on a presentation at the American Association for the Advancement of Science conference earlier this month. The presentation looked at the results of a clinical trial of CAR-T therapy -- some very good results. But this seems like one of those things that has been overblown a little bit by the media. The strong numbers can't be denied, but they need to be looked at a little more carefully. I'm going with my usual mix of hope and caution with this one.


 The presentation, called "Engineering T Cells for Safe and Effective Cancer Immunotherapy,"
took place at the AAAS conference, and described the process for creating the CAR-T cells. The abstract, which is where the link will take you, doesn't get into the results of the clinical trial. Instead, it described the process for creating the T cells. Which makes sense, since the AAAS isn't a cancer-related organization. The speaker, Stanley Riddell from Fred Hutchinson Cancer Center in Seattle, was speaking to scientists, not necessarily cancer researchers.

The Fred Hutchinson News Service sent out a press release about the presentation. It includes a very enthusiastic video describing CAR-T therapy and the success of the trial, and then a more measured text with more detail. The video really is exciting; it shows Dr. Riddell discussing the treatment, and I love to see researchers get excited about their work.

The text, though, quotes Dr. Riddell as saying things like "Much like chemotherapy and radiotherapy, it’s not going to be a save-all," adding, "Some patients may require other treatments." The article also makes clear that 27 of 29 patients with Acute Lymphoblastic Leukemia (ALL) had a complete response, as did 19 of 30 NHL patients (no breakdown of which types of NHL they had). Good numbers, but not a "save-all," as Dr. Riddell makes clear.

There are some other problems, too, with the treatment, including the possibility of Cytokine Release Syndrome, which occurs when too many cancer cells are killed off at once and the body cannot process them all. Two patients in the trial actually died from this. (Some trials are halted when patients die from the treatment or its side effects.) A couple of months ago, I wrote about a CAR-T trial for Follicular Lymphoma, and heard from a reader named Ben who had gone through the trial, and who experienced CRS. (Ben mentioned wanting to start a blog -- maybe we'll hear from him with a link so we can read more about his experiences.)

There are other issues, too. Clearly, with the NHL arm of the trial, it had some good results, also didn't work for about 1/3 of the patients. And it's worth remembering that this was presented at a conference, so it hasn't been peer reviewed (before a medical journal publishes the results, other experts in the area will look it over and make sure the data says what the authors claim it says).

Some other articles take a critical look at the study (and at the overly positive reaction that the media has had to it): The Washington Post's "Why it’s too early to get excited about this ‘unprecedented’ new cancer treatment," and Cancer Research UK's "Immunotherapy cancer ‘cure’ headlines distract from fascinating science." Both of them acknowledge that the research is very promising, but also say, for a bunch of reasons, that we have a while before we know for sure just how exciting this is.

So, as I said, I'm going with "hopeful, but cautious." There's a lot that can happen between a conference presentation and an oncologist's prescription. I hope it all works out as well as it promises.

Wednesday, February 17, 2016

Sequencing Treatments for Follicular Lymphoma

This is a little bit old, but I just came across it this week. It's a video from the conference Lymphoma and Melanoma: An International Congress on Hematologic Malignancies. The Congress actually happened about a year ago, but the video wasn't put up until November (and I'm just seeing it now). I don't usually put things up that are so old (because a lot can change in a year), but really liked the video, and I think the information in it is still current, so I'm going with it.

The video is a presentation called "How Do I Sequence Therapies in Follicular Lymphoma?" and it is presented by Dr. Thomas E. Witzig of the Mayo Clinic in Minnesota. The presentation is meant for oncologists, but the information is fairly easy to understand. Dr. Witzig goes through his process of figuring out which treatments to give to a Follicular Lymphoma patient, depending on the patient's tumor burden and whether or not she has relapsed.

One thing I liked was that Dr. Witzig acknowledged in a small way the emotional difficulty that can come with a watch and wait decision. I think that's something that more oncologists need to understand from a patient's perspective.

He also spends a few minutes looking at recent studies that may show that the first two years after diagnosis are the most important. (It has to do with m7-FLIPI scores.) A patient who relapses within two years might be considered a special subset of FL patient, one who needs to be watched and treated much more closely. He's careful to say those two years are important because it allows oncologists to identify who will need some extra attention.

I think it's important to remind everyone about statistics. The charts that he shows that get into what happens in the first two are important, but they only represent trends in a large group of patients. Statistics aren't fate -- someone who is part of a large group will not necessarily behave the way the rest of the group did. Remember that. (And that comes from someone whose greatest moments of sadness have come from looking at statistics.)

He also spends some time discussing RadioImmunoTherapy (RIT), which has some excellent results, but which isn't used very often (for lots of reasons that don't have to do with its effectiveness, but more with how it is given and how it is paid for). It would be great if there were more oncologists (and patients) looking into it.

And he finishes with some excellent advice for oncologists. First, "Know your patient." He mentioned individualized decisions a few times -- there are lots of options available, but some might be better than others, depending on the patient's situation. I'm all for oncologists listening to their patients and figuring out what the patient needs, emotionally as well as physically. The other great bit of advice: "Don't over-treat." Especially with an indolent cancer, sometimes just enough is the best way to go. I can imagine there is a temptation to say, "Well, four doses worked well, so six might be even better." It's probably kind of an art to figure out when to stop, but it's great to hear that reminder.

So, again, this is one of those videos that doesn't really present anything new -- no groundbreaking treatments that we're hearing about for the first time. But it's nice to see a lot of stuff talked about all at once, and it gives us a few things to think about (like RIT) that we maybe haven't thought about in a while.

Tuesday, February 9, 2016

Allogeneic Transplant A Cure for FL?

Very interesting research from the journal Bone Marrow Transplantation that says an Allogeneic Stem Cell Transplant might cure some patients with Follicular Lymphoma.

There's a lot going on here, and maybe some background information required to understand all of this. It's going to be harder because I don't have access to this journal (and I can't afford to access it), so I'm going only by the abstract to the article (which is called "Allogeneic Hematopoietic Cell Transplantation as Curative Therapy for Non-Transformed Follicular Lymphomas").  I'm going to be very careful about letting you know what I don't know, since I haven't seen the whole article.

First off, a quick review of what a Stem Cell Transplant (or Hematopoietic Cell Transplant) is.

For some blood cancer cancer patients, the best course of action is to essentially wipe out their immune system. If the source of their cancer is their bone marrow, for example, using strong chemotherapy (or other treatment like radiation) destroys the bone marrow and thus the source of the cancer cells. The problem is, the bone marrow is also the source of the immune cells that do the normal job of protecting the body. That means the patient is unprotected while the body rebuilds the bone marrow and the immune cells. On its own, this can take up to a month. A Stem Cell Transplant cuts that time down by putting immune cells into the blood. Instead of a month, the immune system can be rebuilt in 7-10 days, so the body gets protected that much sooner.

Sometimes the immune cells that are put into the body come from the patient (they are removed before the heavy chemo is given) -- this is called an Autologous Stem cell Transplant (or Auto SCT). Sometimes the cells come from someone else (maybe a family member) -- this is called an Allogeneic Stem Cell Transplant (or Allo SCT).

Auto SCT is "gentler" on the body because the cells are already recognized by the patient's body and won't be rejected, which is a danger with an Allo SCT (when that happens, it's called Graft vs Host Disease, and is a very bad thing). But Auto SCT also has the danger of having some of those saved immune cells be the cancer cells that the patient is trying to get rid of, so Allo SCT is often more effective. But either type of SCT has the risk of severe infection if that 7-10 days without an immune system becomes a problem.

(If you want to learn more about Stem Cell Transplants, does its usual good job of giving way more detail than I can give here.)

Now, as far as Stem Cell Transplants being a cure for Follicular Lymphoma, there have been some small studies in the last few years that suggest that this might be true. And this is another one.

Once again, let me be clear that I am only seeing the abstract, a summary of the research, so I don't have all the details. But here's what I can tell:

The researchers are aware that Allo SCT (that is, a Stem Cell Transplant where the cells come from a donor) might cure FL. They are interested in figuring out which sub-groups of patients might benefit most from the procedure.

This is a retrospective study, which means they looked back at patients from the past to see how they did after getting an Allo SCT. The researchers looked at the records of 146 patients from Germany who received an Allo SCT between 1998 and 2008. The Overall Survival for the group was 67% for 1 year, 60% for 2 years, and 53% for 5 years. Those numbers are kind of low for Follicular Lymphoma, but Allo STC is usually given to patients with pretty aggressive disease, so those numbers make sense. 100 Day NRM was 15% (that is, after 100 days, Non-Relapse Mortality, or the number of patients who died from something other than the disease, was 15%. The 100 days is a standard measure, since many problems like Graft vs Host Disease will occur in that time.)

What they found was that certain subgroups seem to do very well with Allo SCT -- those who had limited Graft vs Host Disease issues, were 42 years old or younger,  and who had Total Body Irradiation as their conditioning (in other words, their immune system was wiped out with radiation rather than chemotherapy, or in addition to chemotherapy). This makes sense to me, given what I know about Stem Cell Transplants. Graft vs Host Disease is a big problem, so not having it will be good news. I have heard of oncologists who recommend SCT for younger patients, so that makes sense, too. And I have read that TBI is an excellent conditioning, since it suppresses anything left of the immune system, which cuts down on Graft vs Host, and also kills some cancer cells on its own.

So no big surprises there. But they also say that patients over 55 benefited, too, so that may be the key finding here -- even older folks can be cured (though they recommend patients 42 and under are the preferred group).

So, once again I will say, I haven't seen all of the details here. But the recommendation is clear -- SCT should be considered as a potential cure. But SCT comes with a whole lot of potential dangers, too (again, see the piece linked above), so it's not going to be for everyone.

Given that it's a pretty aggressive approach, it kind of goes against the trend of using less aggressive, more targeted treatments that might control the disease instead of curing it. But a cure is certainly still a valid approach, with the big risks to go with the big reward.

If nothing else, it's a good reminder that we do have that arrow in the quiver -- that option for a treatment that hasn't been talked about much these days.

Thursday, February 4, 2016

Happy World Cancer Day!

Today is World Cancer Day, sponsored by the International Agency for Research on Cancer, which is made up of over 800 cancer-related organizations from 155 countries -- truly a World Cancer Day.

There are lots of events related to World Cancer Day, most of them designed to make people more aware of cancer, its impact, and its prevention and treatment.


The website lists some possibilities for activism, if that is something that you think you would like to be involved in. I sometimes joke about "cancer awareness" -- as if there is anyone in the world who doesn't know what cancer is.

But there really is a lot that people need to be aware of -- new treatments, clinical trials, a lack of funding for cancer research, basic prevention strategies. All of us reading this are, obviously, more aware of cancer than we would like to be. So maybe we can all do our small part to increase awareness. Go on Facebook or Twitter and give people a link to World Cancer Day, or, or some other cancer-related group that means something to you. Maybe ask them to read a little, or maybe make a donation.

It's great that we are aware. It would be even better if others helped us out.

Andrew Schorr, the founder of Patient Power, has a nice blog post about World Cancer Day. He says we should make 2016 World Cancer Year, and really work together to make progress this year toward getting rid of cancer once and for all. I'm with him on that.

In the meantime, take a moment to celebrate. You and your loved ones are survivors.

Go have some ice cream.