Goodbye, Bexxar

Sad news today for lymphoma patients: GlaxoSmithKline is discontinuing its production of Bexxar, the RadioImmunoTherapy treatment that was so helpful to lots of Follicular Lymphoma patients.

There hasn't been a whole lot of fanfare about it; google "Bexxar" and there aren't any press releases or stories about it (at least as I am writing this). But the bexxar.com page does have a brief message near the top of its homepage, that says

GSK plans to discontinue the manufacture and sale of the BEXXAR therapeutic regimen (tositumomab and iodine I 131 tositumomab). The last day to schedule dosing for BEXXAR will be February 11, 2014 with final patient-availability on February 20, 2014.

For more information, contact the GSK Response Center at 1-888-825-5249

That's about it. Though Lymphoma Rock Star Jamie Reno does have an extensive piece on his site about Bexxar and the implications of its discontinuation for all of us. Reno's Follicular Lymphoma was treated with Bexxar in 1999, and he enjoyed a progression-free life for more than 13 years.It's a nice piece, and Reno's anger comes through very clearly.

It's probably not surprising, in some ways, that GSK made the decision. I've written a lot about RIT in the last 5 years -- both the promise it holds and the difficulties it entails. There are reimbursement problems with RIT, which stem from the way it is classified by Medicare. And it's not easy to administer -- not as easy as Rituxan, or most chemos, which can be given right in the oncologist's office. RIT, including Bexxar, needs to be administered by a nuclear medicine specialist, with help from a small team. Kind of a pain to put together, and most oncologists would just as soon do chemo and take care of it themselves. It never really gained the popularity that it should have.

It is also not surprising because GSK didn't seem to make much of an effort to expand its use, unlike the makers of Zevalin, Bexxar's RIT cousin. Zevalin has been involved in clinical trials in the last few years to allow more patients to use it. Bexxar didn't. So, if nothing else, Zevalin's name was out there more than Bexxar's, so more patients might have known about it.

The good news, as I wrote about last week, is that at least one new RIT version is in the pipeline. It has a short wavelength, which makes it (maybe) a little closer to Bexxar than it is to Zevalin. Not necessarily a Bexxar substitute -- I'm mostly looking for things to be positive about.

But overall, there isn't much positive to the news. When more arrows in the quiver bring us hope, this amounts to one fewer arrow.

(I can't end so negatively. There's still a LOT of arrows in that quiver.....)

Bexxar

I write a lot of Zevalin (like I did a couple of days ago), but there's a second RadioImmunoTherapy (RIT) therapy available called Bexxar.


Bexxar works in roughly the same way as Zevalin, but uses a different type of radiation. The choice of using Bexxar or Zevalin depends on a few factors (too technical to get into here). I think we hear more about Zevalin because the rights to it have bounced around a lot, and the company that currently has its rights has been fairly aggressive about getting different approvals for its use. But the important thing is, they both work well.

So I need to give some love to Bexxar, the quiet cousin of Zevalin, too.


Two recent pieces on Bexxar:


The first is an article from the most recent issue of the medical journal Current Oncology called "131I–Tositumomab in Lymphoma." (131I–Tositumomab is the real name for Bexxar.)

Of course, the best part of the piece is that one of the co-authors is J. A. MacEachern from McMaster University in Canada.

The article is a review of 18 clinical trials on Bexxar, and looks at trends in the trials. Bexxar shows a complete response in 65-72% of Follicular NHL patients who had been previously treated. The authors think Bexxar is a promising treatment, especially as an option for patients who have not had success with chemo.


Which was the case with Jamie Reno, whose name has come up before in Lympho Bob (a link to a piece in Newsweek, where he interviewed Farrah Fawcett's oncologist soon after she died, in which the doctor gave passionate support for RIT.) Jamie tried the chemotherapy treatment CHOP in 1996, but had his fNHL come back three years later. Doing extensive research on his own, he decided that Bexxar was his best option. He writes about it in an article on the web site called LymphomaInfo.com called "Radio-Immunotherapy Saved my Life." It's an easy read, and makes the point pretty clearly about RIT's usefulness. He points out that results from a Bexxar trial will be available next year, and may lead to Bexxar getting the same front-line status that Zevalin now has.


Here's to hope.

Bexxar Problems

I've written a lot about RadioImmunoTherapy (RIT), particularly one of the two types, Zevalin. I don't mean to ignore the other type of RIT, Bexxar, but there's been so much more news about Zevalin in the past few years that it's been easy to ignore Bexxar.

Which brings us to a problem: drug maker GlaxoSmithKline announced last week that it will severely cut back on its production of Bexxar, which will make it very difficult for some patients to get access to it.

This is not good. Bexxar and Zevalin work in similar ways, but they are pretty different -- different enough that losing Bexxar will create potential problems for lots of patients. For example, both types of RIT are essentially monoclonal antibodies with a bit of radiation attached to them, so when they bind to a specific protein on a lymphoma cell, the radiation can zap it. (Here are some other differences between Bexxar and Zevalin, courtesy of lymphomation.com)

Here's where the problem lies: Zevalin is basically radioactive Rituxan, currently the most commonly-used monoclonal antibody. But many patients who use Rituxan alone and as part of chemo can become resistant to Rituxan. So there's a chance that they will be resistant to Zevalin, too. Having another RIT option like Bexxar may save them (as it has saved many others) when Rituxan-containing treatments stop working.

Naturally, the NHL community is up in arms about this. GSK has every right to cut down or stop production if people aren't using Bexxar. However, GSK hasn't done a whole lot to market Bexxar, either, so NHLers are feeling a little betrayed. And they've become very vocal about this. For example, it didn't take too long to reach 1200 signatures on a petition to GSK to save Bexxar.

I think they're unlikely to change their minds. RIT, for all kinds of reasons I've discussed here in the past, just isn't widely used, despite its well-documented successes. I think what we can hope for is that GSK sells Bexxar to someone who's more willing to push it. That's exactly what's happened to Zevalin, and sales picked up as a result.

Keep your fingers and lymph nodes crossed....

Good Bexxar News

This year's American Society of Hematology (ASH) Conference takes place in a week or so, and they've already put up abstracts for the presentations on research for various blood disorders. I'm sifting through it all, and I'll try to comment on some of the more interesting ones. I may end up waiting until after the conference; that's when drug companies start putting out press releases, and medical web sites start commenting on important items from the conference. All of that helps put it in perspective.


But there are a few really good ones that are worth posting now, inlcuding this one: Since I've been giving Bexxar some love lately, it's nice to see positive results.


Here's the abstract from the ASH conference web site. The presentation is called "Tositumomab and Iodine I-131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma: Median 10 Year Follow-up Results," and it discusses how well a group of Bexxar patients from 1996 to 2009 have been doing.


Very encouraging results. A total of 76 patients (all but one had Follicular NHL) were given Bexxar. 97% of the patients achieved a response, with 75% achieving a complete response (all traces of the lymphoma were wiped out by the Bexxar). Patients had been given Bexxar anywhere from 1 to 12 years before the results were measured, with a median of 10 years (that is, half had taken it more than 10 years ago, and half less than 10 years ago).

The median duration response was 6 years (half of the patients didn't get worse after that time). 40% of patients were progression-free after 10 years. For that 75% who had a complete response, the median progression-free state was almost 11 years.


Pretty good numbers, I'd say; lots of patients have done very well over the long term with Bexxar. The study isn't perfect (there's a pretty wide range of years involved, making it harder to really measure long-term impact; it's a single-arm study, which means they didn't compare Bexxar with some other treatment in the same study), but it's encouraging.


More evidence for people to consider RadioImmunoTherapy, if nothing else.

End is Near for Bexxar

This is almost two weeks old, but Jamie Reno published a nice piece for the International Business Times on the demise of Bexxar, the RadioImmunoTherapy treatment that will be discontinued by GlaxoSmithKline on February 20.

Reno focuses on the issue of profits vs. people. Bexxar has proven to be very effective, especially over the long-term (and Reno is himself an example of that), but is more difficult to administer than Rituxan or traditional chemo. As a result, despite its good track record, Bexxar hasn't been used as much as other treatments. So GSK is giving up on it (rather than, say, selling it to another company who might put more effort into marketing it). It means another option is gone for Follicular Lymphoma patients. Profits weren't there, so people suffer.

Read the article. Reno does a nice job of laying out the issues. (That's why he's a Lymphoma Rock Star.)

I get the feeling that, despite their successes, RIT is on its way out -- Zevalin and another being developed. Particularly with newer Kinase inhibitors, anti-PD1s, and vaccines being developed, something as complicated (or perceived to be complicated) probably isn't going to be pushed up the preference list. If we're lucky, Zevalin will at least stick around, so the option will be there if we need it.

That's a little pessimistic, I know, but we still have lots of options, with more on the way.

(And I'm going to have to stop there. Stiff shoulder. Maybe that's contributing to my pessimism?)

Follicular Lymphoma: The Best of 2013

For the last 3 weeks or so, I've been seeing lots of end-of-the year lists, proclaiming the best of, or the worst of, or the top whatever: Sports Illustrated's top sports moments of the year, for example (one too many sad Boston sports moments in there), or Ralfy's Single Malt Scotch of the Year for 2013 (an excellent choice).

I thought it might be fun to put together my own "Top 10" list for Follicular Lymphoma. Despite what the blog post title says, this isn't necessarily the ten "best"; it's not even the ten most significant. More like the ten that struck me most.

I know some of these end-of-year lists are designed specifically to get people discussing, and this one is probably no different. So feel free to argue for a different order, or to leave some things out altogether and suggest new ones.

Here they are, in descending order:

10) Approval Sought for Idelalisib/CAL 101 for Indolent Lymphoma. This could potentially be higher that #10, but I'll let you fight that out. Gilead, manufacturer or Idelalisib, submitted an early application to the FDA, based on phase 2 clinical trial data. Significant for a couple of reasons: it's the first kinase inhibitor to go through the process, and an approval could bolster other phase 2 data-based applications (and maybe speed things up for other treatments). I've been following this for a little while, because some support group folks were in the trial, and were having some great success.


9) Ibrutinib Makes Everyone Lose Their Minds with Excitement. The FDA approved Ibrutinib for Mantle Cell Lymphoma patients in November, giving it "Breakthrough Status" and approving it early. It also achieved a 100% response rate in 15 patients (10 complete, 5 partial) when combined with CHOP in DLBCL patients in August. It's currently in a phase 2 trial for Follicular Lymphoma, and its mind-loss-causing abilities seem like they might be justified.

8) GA101 plus CHOP Kicks Butt. Results of a phase 2 trial of Follicular Lymphoma patients showed that G-CHOP achieved a 93% response rate. GA101, also known as Obinutuzumab, seeks to be an improvement on Rituxan; it is humanized (no mouse parts) and glyco-engineered (designed to latch on better). A phase 3 trial seems to be justified.


7) Some Guy Stays Alive for 5 years and Thinks He's Special. I wanted to include someone telling his or her story of being a Follicular Lymphoma patient, and I thought, "Why not me?" So here's my Lympho Bob entry from last January 15, when I celebrated my 5 year Diagnosiversary. It might seem a little pompous, but it's really quite the opposite -- take it as an example of my humility and self-control that I didn't put myself higher. (And yes, I beat out the other three, because none of them are FDA-approved for FL yet. At least I did something...)

6) Learning from Cancer. OK, so my own story isn't the only one to make the list. I have to include something from Michael Buller's Thinking Out Loud blog. My all-time favorite post of his is his Top 10 Perks of Being Treated for Follicular Lymphoma -- funny, insightful, very positive and hopeful -- but written in 2012. My favorite from this year is 10 Things I've Learned from Cancer -- equally insightful and inspiring truths -- lessons that I hope any newbies learn along the way. (Bonus: there's a part 2.)

5) Transformation no so common? This one is exciting and hopeful, but worth being cautious about. Researchers found that the overall transformation rate for 600+ Follicular Lymphoma patients was under 11%, far less than the 30% that seems to be the consensus. Excellent news, but I've seen the figure anywhere from 15% to 50% of FL patients will transform. This gets #5 based on the hope it inspires, but I'm still not sure we're suddenly that low.

4) Bye Bye Bexxar. This is why it isn't really a "best of" list -- Bexxar, one of our RIT options, is not going to be made anymore. Nothing worse than our quiver being an arrow short. Jamie Reno (speaking of "best of") wrote about his own experience with Bexxar, and his disappointment, in reporting on the decision. Plus, Jamie's just worth reading. You won't find too many better writers on cancer.


3) Bendamustine Kicks Butt Even Better than CHOP.  A researcher team has been pitting  Bendamustine against R-CHOP for several years: head to head, mano a mano, B cell to B cell. After giving updates at conferences, they finally subjected their results to peer review. Bendamustine won big -- better results with fewer side effects. Probably cemented Bendamustine + Rituxan as the preferred first treatment for Follicular Lymphoma (along with Watching and Waiting, straight Rituxan, and a bunch of other things). Worthy of the bronze medal.

2) Survival Stats. When I was first diagnosed, someone wrote to me to tell me how worried he was that Wikipedia said that the Median Overall Survival rate for FL was 8 to 10 years. Those are complicated numbers to calculate and to explain, but they were fairly accurate -- for 1997. There is some suggestion that our current median Overall Survival is at least 18 years, and likely higher. Lots of reasons that number is also complicated (starting with the ways "median" and "overall survival" are defined), but the number makes my heart skip a beat in a good enough way that it's staying at #2.

1) Rituxan + Pidilizumab for Follicular Lymphoma. I'll admit to a bit of "recency bias" -- the stuff we have experienced most recently is the stuff we tend to believe the most. And since this bit of news came less than a month ago at the ASH conference, I might be giving it too high a ranking just because it's fresh in my mind. But given how excited people are about T-cells and Immunotherapy, I think this one holds the most reason to be excited. Rituxan gets a new best pal in Pidilizumab, which tells T cells to get off the couch and do their job. Extra points for being part of a larger trend, but ultimately the one on the list that gets me most excited.

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So while there might be some argument about the list, there's no argument that this was a damn good year for Follicular Lymphoma. We have some pretty special stuff in the pipeline, and even if only a small percentage lives up to its promise, we're in for a bright near future.

Thanks for a great year, everyone. I hope next year is good to you all.

Image of the Year

The organization SNM has named its "Image of the Year," and the award goes to this image showing the effectiveness of RadioImmunoTherapies (RIT) Bexxar and Zevalin (of which I have written fondly many times in the past):




Isn't it beautiful?


The images are from PET scans that show reduced cancer activity (the dark spots). The first two are the Before and After for Bexxar, and the third and fourth are for Zevalin. You can see the reduction of dark spots (not all the spots are cancerous).


The image is from a study at Stanford that looked at Bexxar's and Zevalin's effectiveness for patients with relapsed NHL. You know how RIT works: it identifies b-cells and kills them off with a shot of radiation delivered right to those cells. The overall study confirmed the effectiveness of RIT for many patients, and the lead invesitigator is excited to see how RIT works as a first treatment for NHL (it's only approved now for patients who have already received another treatment and had it return).


Very encouraging, as always. Despite RIT's strange reimbursement structure and complexity in administering, the article points out that RIT treatments cost about half of what a course of chemo costs, so maybe insurers will start pushing it more. I hope so. It's too good a weapon to ignore for bureaucratic reasons.


SNM, the organization that gave out the image award, is "an international scientific and professional organization of more than 16,000 members dedicated to promoting the science, technology and practical applications of molecular imaging and therapy and nuclear medicine to diagnose, manage and treat diseases." Nice to know there are so many people who think so highly of RIT. I hope they'll push hard for more widespread use.


Interestingly, I looked at SNM's web site for about 20 minutes, and couldn't find anything that told me what "SNM" stood for, so the site is either really poorly written, or they just think it's neat to have only initials, like LL Cool J (Mama said knock that cancer out!). But I did find out that you can get an SNM hat or "cardiac necktie" in either gray or blue, with a repeating pattern of a diagnostic image of a heart. (Keep in mind, though, that the tie is $6 cheaper if you're a member of SNM.)

ASH Preview: Zevalin

As I said I my last post, when I do previews like this for the ASH meeting, I'm not trying to be comprehensive. If something seems important, I'll look at it. (You'll see a few of those coming up.) But if something seems interesting t me personally, I'll look at that, too.

This is one of those "interesting to me personally" previews. It's for session #1825 "Real-world outcomes of Y90-ibritumomab tiuxetan (Zevalin) in low-grade B-cell non-Hodgkin lymphoma: A single-institution experience."

Zevalin is a type of RadioImmunoTherapy, or RIT. You don't see much about RIT anymore, at least not in the U.S., and there's a reason for that. RIT treatments were created to solve a problem with blood cancers in using radiation. Radiation can be an effective treatment, particularly for cancers with solid tumors. A beam of radiation can be aimed directly at a tumor. But that's not the case with blood cancers -- the cells are always moving around in the bloodstream, so it is literally a moving target. RIT works by taking a monoclonal antibody (something like Rituxan), which targets a protein on a cancer cell (CD20 is the target for both Rituxan and Zevalin). It also includes a small bit of radiation. So when the RIT finds a CD20 target, it attaches itself to the cancer cell, putting the little bit of radiation onto the cancer cell and killing it. And even better, at least in theory, because the radiation is aimed at a very specific target, there is less chance of it affecting healthy cells, so there should be fewer severe side effects. 

Zevalin was approved by the FDA for Relapsed and Refractory Follicular Lymphoma in 2002, and another RIT called Bexxar was approved right around the same time. I was diagnosed in 2008, so there were lots of follow-up studies being conducted and reported on in those first few years after I was diagnosed. And it was all very exciting to me. I remember the first article from a medical journal that I really got excited about was a report of R-CHOP and Zevalin, where Zevalin was used a salvage therapy (that is, it was given after R-CHOP to kind of clean up any leftover cancer cells). The idea of using three different treatment types -- a monoclonal antibody, traditional chemotherapy, and an RIT -- that work on the cancer cells in different ways, just made so much sense to me. 

So Zevalin has been on my mind for almost as long as I have been an FL patient. And those early studies showed that it was very effective. I remember communicating with two or three folks who had been in trials for Zevalin, and who had been in remission for years.

So why do we hear so little about it now?

Well, at least in the U.S., it's for a couple of reasons, but the biggest was a ruling by the FDA about how Zevalin had to be administered. Because it involves some radiation, the FDA ruled that it could only be administered by a Radiation Oncologist, someone with about 400 hours of specialized training. So while Rituxan or CHOP can be administered right in the treatment room at an oncologist's office, they would need to send you to a specialist if they thought RIT was the best option. And even in 2008, there were already a number of other options for FL treatment, so there wasn't much reason to send a patient to another specialist, or to do 400 hours of specialized training themselves. 

Soon after that ruling, the maker of Bexxar pulled the treatment from the market.But Zevalin has stuck around.  I have no idea how often it is used these days, but as far as I know, it's still available. Interestingly, a few years ago, there was another attempt at getting an RIT approved. It was called Betalutin, and it was pulled after a phase 2 trial. I kind of predicted that was going to happen when I first started reading about it.  

So what is this particular ASH presentation about?

Well, it looks at "real world" outcomes for people who received Zevalin -- patients who were not in a clinical trial. Some of those folks were followed for 22 years, from the time Zevalin was approved by the FDA.

A total of 122 patients with B Cell Non-Hodgkin's Lymphoma (most of them had FL) from one cancer center were followed. 72 of them had received one previous treatment, 43 used it as a salvage therapy after chemo, and 6 used it as a first treatment. The median age was 64 years old. 

The Overall Response Rate was just under 78%, which is pretty great for an FL treatment -- 70.8% ORR for the R/R patients, 88.4% for the salvage patients, and 100% for the first treatment patients.

The media Overall Survival was just under 10 years for the whole group. (Remember, Overall Survival measures dying from any cause, not just something Lymphoma-related, and "median" means that half of the group lived less than the median number, but half lived more than the number.) The median OS was 6.5 years for the R/R group, 15.2 years for the salvage group, and 8.4 years for the first line group. The median time to next treatment was 7.4 years, and 18 patients developed a secondary cancer.  

In their conclusion, the researchers say that Zevalin still has a place in the treatment options for certain patients. That's probably true, especially considering it is about the same cost (maybe even a little cheaper) than something like Rituxan. But I also think it's very unlikely that it's going to suddenly get popular, given all of the other treatment options we have now.

It's always interesting to look back and think about what might have been. I certainly don't have any regrets about being treated with Rituxan instead of something else. But I also can't help but wonder what the path for other FL patients would have been if Zevalin had become more popular. It's not a perfect treatment, by any means, but it might have helped a lot more people than it was able to.

More ASH previews soon.

 

 

 

 

 

Immunotherapy

ASCOPost, an online publication from the American Society of Clinical Oncology, featured an interview a few weeks ago with Dr. David Porter, who is doing some interesting work in Immunotherapy, specifically with Leukemia patients. He talks about some of the advances in Immunotherapy that have come about in the last few years, and speculates about advances in the fairly near future.

Immunotherapy, basically, is the use of the body's own immune system to fight off cancer. Probably the best known Immunotherapy for Follicular Lymphoma patients is Rituxan, which works in several ways, all of which work with the immune system to kill off the cells. Cool video alert! 

As Dr. Porter makes clear, immunotherapy works because the treatment finds a target that is unique to the cell. (Rituxan finds CD20, which is present on B cells, the white blood cells that get all cancery.)

The challenge over the next 10 years, says Dr. Porter, will be in finding the targets on those cells.

I think that's less of a problem for Follicular Lymphoma. We've had some pretty great success with CD20. In addition to Rituxan, it is also the target for Zevalin and Bexxar, the RadioImmunoTherapies (I refuse to let Bexxar die, even if the current owner is going to stop manufacturing it), and the monoclonal antibody Ofatumumab. We also know that Follicular Lymphoma cells express CD10, CD19, and CD22. That's a bunch of targets, and already a bunch of treatments available and in the pipeline to go after them.

My guess is, given that we're ahead of a lot of other cancers when it comes to immunotherapy targets, our goals for the next few years will be 1) developing more and better immunotherapy agents. So far, nothing seems to beat out Rituxan enough to make us want to switch over. And with cheaper generic versions of Rituxan on the horizon, we're going to need something big; and 2) we're going to need to find some combinations of immunotherapies or other agents that show improvement over what we have (R + R, Rituxan + Revlimid, comes to mind).

(By the way, don't you love how I say "We," as in "We need to develop better treatments," like I'm in a lab coat looking through a microscope? I think it comes from it being baseball playoff season, as in, "We can't allow the Rays to win in the ninth like that again." Put me in, coach.)

Speaking of combinations, the other interesting comment that Dr. Porter made had to do with chemotherapy. It's not going anywhere, he says. I think he's right.

I've made snarky comments about clinical trials with CVP and Fludarabine, and how out-of-fashion they are, but my point isn't that they shouldn't be used anymore. It's that trials should be focusing precious resources on newer, more promising, focused treatments. (Which is actually the case -- I don't know of any brand new trials for older chemos, other than CHOP and its variants, or Bendamustine.)

Chemo is here to stay for a while, because it works, especially with refractory patients. Finding a good immunotherrap-chemo combo is the trick (R-CHOP and R-B certainly are proving effective). So is using immunotherapy agents to deliver targeted doses of chemo, rather than relying on the scattershot approach that traditional chemo takes.

So, while the interview wasn't focused on Follicular Lymphoma, it still provides some food for thought.

Promising RIT for Follicular Lymphoma?

There's a new cowboy in RITville.

(OK, that metaphor isn't my best. I'm on vacation.)

There's a new version of RIT that may be available at some point. Results from an early clinical trial look good.

RadioImmunoTherapy (RIT) is a fairly effective, but fairly underused type of treatment for NHL. Right now, there are two versions of RIT available, Bexxar and Zevalin. They are both effective, and have some differences between them that make the choice of one or the other better for some patients. (Lymphomation does an excellent job of comparing the two, which isn't surprising, because they do an excellent job at pretty much everything.) RIT works by providing radiation to lymphoma cells. Because blood cancer cells are moving targets, traditional radiation treatments don't work. So RIT treatments use something that can find and attach themselves to cancer cells (like Rituxan) and have that molecule carry a tiny dose of radiation, delivered directly to the cancer cell. Pretty cool system.


The current issue of the Journal of Nuclear Medicine reports on the results of a clinical trial for a version of RIT that uses luteum-177, added to Rituxan, as its delivery method. Lu 177 differs from the other RIT types because it doesn't penetrate tissue as deeply (and therefore won't travel too far beyond the targeted cancer cells, sparing more healthy cells).

The purpose of this trial was to determine the best dosage for this treatment, and it seems like they got decent results -- about 52% of patients got a response (29patients overall; 6 had a complete response and 9 had a partial response).

However, the results for the group of patients with Follicular Lymphoma were particularly good (it "appeared to have striking activity in follicular lymphoma," said the authors). of the 11 patients with FL, 9 had a response, for an 82% response rate. Excellent.

It's an early study, so it will need to go through more steps, and recruit more patients for tests. And then, there's the whole issue of whether or not it will be practical -- that is, whether or not it will run into the same problems as Zevalin and Bexxar, with their reimbursement and logistical problems. But maybe this will be the one that gets some attention and forces a re-evaluation of the uses of RIT.

Betalutin (RIT) Trial for FL Has Been Stopped

The company that makes the RadioImmunoTherapy (RIT) treatment called Betalutin has decided to stop its phase 2 trial for third line Follicular Lymphoma treatment. I'm a little sad about it.

Sad, but not really surprised -- I've been saying for a while that I thought Betalutin would face some challenges. RIT treatments just require too much work in the U.S. But what surprised me was that its most recent results showed good safety and decent effectiveness, but "decent" isn't good enough.

A little background, to remind you, since I haven't written about Betalutin in a while:

RadioImmunoTherapy treatments are kind of a combination of monoclonal antibodies (like Rituxan) and radiation therapy. Radiation is not common in Follicular Lymphoma and other blood cancers because it works best when the cancer cells stay still, as they do in solid tumors like lung cancer or colon cancer. Blood cancer cells move around through the blood constantly. A beam of radiation won't work. 

So what if you could take the radition directly to those moving cells? That's what RIT does. It takes something like Rituxan, which seeks out B cells by attaching itself to a protein on their surface, but it adds a little bit of radiation to the Rituxan. So you have a package of radiation delivered right to the cancer cell. 

In theory, it means fewer side effects, since the radiation goes directly to the cancer cell. And it means it's effective, for the same reason -- the treatment has a specific target. 

And RIT is indeed effective. In the past, two RIT treatments were approved by the FDA for FL -- Zevalin and Bexxar. However, in the U.S., rules for treating patients with RIT are complicated. Because it is radioactive, it requires special training, so regular oncologists can't give it patients (unlike traditional chemo or immunotherapies). With so many other effective options, most oncologists don't send patients to RIT specialists without some really compelling reason.

So RIT is use much less often than it should be, given how safe and effective it is. Bexxar wasn't used often enough to stay around, and it was discontinued in 2013. Zevalin is still around, and researchers continue to provide data that shows it is an excellent option (most recently in April). But it is still used much less frequently than it should be.

So, as I said, I'm not surprised that Betalutin isn't going to be an option for us (though the manufacturer is looking at other ways to offer it, maybe in combination with other treatments). Only about 33% of the 109 patients in the trial had a response that lasted more than 6 months. That's not great, especially when compared to CAR-T and bi-specifics. 

So why am I a little sad about this? It's personal, I guess. Zevalin was approved in 2009, the year after I was diagnosed. I think it was probably the first FL treatment to get FDA approval during the time I started really paying attention to that kind of thing. I know a couple of people who had Zevalin early on and who had great success -- over 15 years in remission. So I've always hoped that RIT would catch on.  But I can't imagine any one else will make an attempt to bring RIT to the market at this point. The field has moved on.

One last important point. It seems like I've been writing a lot lately about treatments have not been successful . That's true. But I don't think that means that more treatments are failing. If anything, it means that there are more high profile treatments that are being talked about early on in the trial process, and that I am writing about them. Remember, less than 10% of cancer treatments ever make it to a phase 3 trial. The great majority of them don't show enough effectiveness or safety in phase 2, phase 1, or (especially) pre-trial results to move forward.

My point is, there are still lots of treatments available to us, and lots more to come. 

I'll move on from my little bit of sadness. There is so much more to come to be excited about. And I'll keep sharing what I learn.

CHOP vs RIT: Long-Term Results for FL

Hot off the presses:

The Journal of Clinical Oncology just posted an abstract for "Continued Excellent Outcomes in Previously Untreated Patients With Follicular Lymphoma After Treatment With CHOP Plus Rituximab or CHOP Plus 131 I-Tositumomab: Long-Term Follow-Up of Phase III Randomized Study SWOG-S0016."

The article reports on a 10 year follow up of a randomized trial. Half of the 531 patients were given R-CHOP, and half were given CHOP + RIT, or RadioImmunoTherapy, in this case ¹³¹I-Tositumomab, also known as Bexxar.

(If you need a reminder: RIT is kind of a super-charged Rituxan. Imagine a dose of Rituxan, which seeks out the CD20 protein on FL cells. But now add a drop of radiation to each bit of Rituxan, so those cells get the radiation delivered right to them.)

Over 10 years, the Progression-Free Survival was 49%, and the Overall Survival was 78%. The CHOP-RIT group had a better PFS than the R-CHOP group (56% vs 42%).

But there was no significant difference in Overall Survival between the two groups.

There was no difference in the incidence if secondary malignancies or myelodysplastic syndrome (sometimes called pre-leukemia) or acute myeloid leukemia (an aggressive type of leukemia). But there was a higher incidence of death from MDS and AML in the RIT group.

 The researchers conclude that all of this points to Immunochemotherapy (R-CHOP in this case, but also R-Bendamustine and maybe CHOP or Benda + Obinutuzimab) remains the best choice for high-risk FL patients for a first treatment.

Two reasons for this:

First, there are the problems with RIT. Studies of RIT showed a great response -- about 70%. As this study shows, the response is not only broad, but durable -- patients can go a very long time without another treatment (the FL patient and advocate Betsy de Parry has gone over 15 years since her RIT treatment). But problems with payments and administration have made it underused (see the discussion of RIT at Lymphomation.org). It's so underused that Bexxar isn't even available anymore. It's a real shame.

And the other reason is the lack of difference in Overall Survival. If there is no difference in OS, there is no reason to go through the difficulties that come with administering RIT.

Two thoughts from me as I read this, for what they are worth:

1) It's pretty frustrating to read so many research reports that compare treatments, and have none of them show an Overall Survival benefit greater than the others. There has to be something out there that breaks through all of this. I don't know if it will be a single treatment or a combination, but I hope that something, at some point, breaks from the pack. Maybe it's already out there, in a clinical trial somewhere. It's a good reminder that we need to keep trials in mind when it comes to decisions about treatment -- there's no way to get new treatments without people to test them. (And since I have the Lymphomation.org page open, here's a link to their Clinical Trials page.)

2) It's also frustrating to see RIT be so successful, but see it so underused. I have a kind of emotional attachment to RIT. Another RIT, Zevalin, was approved a couple of years after I was diagnosed, and I remember being really excited about it. Over the next few years, I saw all the problems it was running into. Frustrating.

I talk a lot about "having more arrows in our quiver." That's the phrase that was used by the Lymphoma specialist that I saw a few days after I was diagnosed. He was talking about treatments available, and how each new treatment was another weapon available to us -- another arrow in the quiver. I've always thought that more arrows, more available treatments, was better for us. If the F;l comes back, there's something else to try.

I'm getting to the point where I don't want more -- I want better. I'd be pretty happy with fewer choices if those choices were personalized, and I knew they had a good shot at working for me, individually, based on the biomarkers that get found on my cells.

But that's a hope more than a reality, at least for now. I'll stay satisfied with my quiver full of arrows, trusting there's another one there when I need it.

In the meantime, I'll keep reading and reporting. And staying hopeful.

Zevalin and Follicular Lymphoma

The Journal of Clinical Oncology published an article earlier this month on the effectiveness of Zevalin. The article is called, quite simply, "90Yttrium-Ibritumomab Tiuxetan Consolidation of First Remission in Advanced-Stage Follicular Non-Hodgkin Lymphoma: Updated Results After a Median Follow-Up of 7.3 Years From the International, Randomized, Phase III First-Line Indolent Trial." 


I'll translate: "Using Zevalin as an immediate follow-up to successful first treatment for Follicular Lymphoma Patients: We've been doing this for over 7 years and it's working, blah blah blah."

Some background, first, because I haven't really discussed Zevalin recently, and I apparently have a bunch of new readers.

Zevalin, along with Bexxar, are known as RadioImmunoTherapy treatments (RIT). RIT is a pretty successful way of battling Follicular Lymphoma. It basically uses Rituxan, which seeks out the CD20 antibody on FL cells and attaches itself to them. but what makes Zevalin (and Bexxar) different is that they add a tiny bit of radiation to each molecule of Rituxan. Traditional radiation doesn't usually work in FL, because the cells are traveling through the blood stream. Since Rituxan seeks out individual FL cells, it can deposit that bit of radiation on the cell. Healthy cells are more likely to be spared.

Early studies of Zevalin were extremely positive: very effective, with fewer of the side effects of traditional radiation (since it's targeted). The FDA approved it as a consolidation therapy -- basically, something that could be used immediately after another treatment to make sure all the FL cells got killed off. There was a lot of talk a few years ago, after the FDA approval, that a three-way treatment strategy might be the way to attack Follicular Lymphoma: a chemo/Rituxan cocktail, with a Zevalin chaser. Chemo, Rituxan, and Zevalin work in three different ways, so maybe that approach will finally be the thing that fools the FL cells?

There's been less talk of that lately, as traditional chemo seems to be dying off as a future focus. And Zevalin never really got the traction it should have gotten, given how successful it was in early trials. There are a few reasons for this, and they have nothing to do with its actual effectiveness. Zevalin can't be administered in an oncologist's office; it has to be done by a special team of nuclear medicine specialists, given that it is radioactive. Plus, there's some kind of Medicare-reimbursement issue that I don't fully understand that discourages doctors from using it. So, basically, there are monetary and political issues that keep it from being used, even though Zevalin is an effective treatment.

And the JOC study does confirm that Zevalin is effective. This article is actually one of the few long-term studies Zevalin. It looked at 409 patients with advanced Follicular Lymphoma who had a full- or partial-response to their first treatment. Half were given no treatment, and half were given Zevalin as a follow-up. The patients who got Zevalin fared much better. After 7.3 years, 41% of those patients had not had any additional growth in their cancer. Only 22% of the non-Zevalin patients had similar results.

If you don't want to wade through the original article, Cure Today has a nice summary.

I like to think that results like this will spark more of an interest in Zevalin, though I get less optimistic about it as time goes on. Which is a shame, because the idea that we are treating with such a different mechanism than other treatments is really attractive. Maybe, as combinations of newer treatments are being tried out, someone will decide to return to Zevalin as a consolidation treatment, and we'll see some great things happen.

In the meantime, it remains another arrow in the quiver, and we can never have too many of them.

Treatments in the News

First, a musical update:
On Saturday, Peter played alto sax at the FMI All-State Band concert. This involved over 300 kids from Catholic schools around the state. Four bands played; Peter had auditioned and was placed in Symphonic Band, second highest of the four. He did a great job. It's rare for a fifth grader to make that band, so we're very proud of him.

The kids got their scores from the Connecticut Young Musicians Festival, where they all played piano. All three of them scored a 4 out of 5, so all of us are pleased. Catherine has been playing less than a year, so that score was great. And John and Peter both played some challenging pieces, so their scores were great, too.

Such talented children. I can't even read music, so I can take no credit for all of this.

*************************

I listened to a really interesting webcast on follicular NHL yesterday, with a doctor from Rochester, NY who is a specialist in this lymphoma. [I can't get the link to work, so I can't let you listen to it.]

He talks about some of the promising treatments for follicular NHL. Thought I'd share some of what he said:

The standard treatment for a long time was a chemotherapy called CHOP, which stands for four different drugs. In the last 10 years, it has been CHOP-R, which is CHOP plus Rituxin, a monoclonal antibody which works by seeking out a specific protein (CD20) that is present on the B-cells that are affected by certain lymphomas. Rituxin is also used on its own with some effectiveness. One of the great things about Rituxin is that is has almost none of the side effects that chemo has. This drug alone has almost doubled the survival rates for fNHL patients.

Rituxin has been used for about 10 years, and in that time, researchers have built on this technology in other ways. Two other drugs called Bexxar and Zevalin also target CD20 proteins. But the twist is that they have a tiny dose of radiation, so they zap the B-cells when they find them. This is a huge advance. Traditional radiation treatment targets individual tumors. Lymphomas are harder to use radiation on because the "tumors" are cells that travel through the blood -- nearly impossible to pin down. Bexxar and Zevalin allow the radiation to get to where they need to go. The treatmnent takes only a week (versus months for chemo). The downside is that, because it's radioactive, a special team needs to be assembled to administer it. No going to the office and letting an onc nurse do it. So they've been underutilized so far. Yale, however, has offered the treatment in the past.

Another drug being tested now is called Revlimid. It has been approved for use on patients with Multiple Myeloma, another blood cancer, a "first cousin" of follicular NHL. This one works in a different way than the monoclonal antibodies. There is some research that suggsts that certain abnormalities of the blood vessels may support cancer, a possible reason Multiple Myeloma (and perhaps indolent lymphomas like follicular) are so hard to wipe out. Revlimid targets the blood vessels, creating changes in them that may wipe out whatever property is getting in the way of killing off cancers.

Another Myeloma drug being tested on fNHL patients is Velcade. This takes yet another approach to the disease. It is a Proteozome inhibitor. As the webcast describes it, every cell has a "wastebasket" that collects waste products that occur when a cell takes in nourishment; the wastebasket is then emptied into the blood, where it gets expelled. Velcade shuts off the "emptying" feature of the wastebasket. All of the waste builds up in the cancer cell, and it eventually kills itself. It's kind of a poison that is already present in the cell.

Yet another group of drugs in development is called BCL2 inhibitors. BCL2 is a protein that keeps a cell from dying. When the cell runs out of the protein, it dies -- this is a normal thing. All cells die. In lymphoma cells, particularly in indolent lymphomas like follicular, there's too much BCL2, so the cell takes a long, long time to die (and it's really hard to kill off). The BCL2 inhibitor would tell the lymphoma cells to stop producing so much of the stuff, so they would either die a "normal" death, or be easier to kill off with Rituxin or some other agent. These drugs are in early trials, so probably 4 or 5 years away from approval. But this is most promising, if it all holds up as well as it has so far in early tests. The really cool part of this? It's a daily pill -- no chemo, no injections.

That's kind of the theme in lots of these potential treatments: unlike chemo and radiation, there are fewer, less harsh side effects. And more importantly, more options. Follicular NHL, as I've written once before, is the "Tarzan" cancer -- there are always more vines to grab on to, more treatments to try. Some treatments work for some people; other people won't stay in remission and need to try something else. But it usually grows so slowly, there's time to try other things.

The researcher being interviewed was very excited about it all, and I'm excited about it all, too. It's bringing out that inner scientist in me. Makes me wish I stayed pre-med for more than one semster....

My Buddy Z

....By which I mean Zevalin, the RIT (RadioImmunoTherapy) treatment that I've written about several times before. More good news about its effectiveness.


To review: "Liquid" cancers like NHL are hard to treat with radiation because the cancer cells don't hold still -- there's nothing to aim the radiation at. The development of Rituxin, an antibody that recognizes B cells (including the cancerous ones) and attaches to them, was a huge advance for lots of reasons (and even more reasons are popping up). Zevalin (and its cousin Bexxar) are basically radioactive Rituxin -- Zevalin attaches itself to the B cells and delivers a dose of radiation to them. It's a pain to administer (you need to assemble a team of nurses, radiologists, and nuclear medicine specialists to do it), but in theory, it's a great therapy, combining a couple of different types of treatment. But studies are trickling in to show that it's meeting that great theoretical promise.


The October issue of the Journal of Clinical Oncology includes an editorial from Oliver W. Press, a researcher from the Fred Hutchinson Cancer Research Center and University of Washington in Seattle. (He's a big name from a big research center).


In a nutshell, Press reviews a couple of recent clinical studies of Zevalin, and while he points out some problems with the ways the studies were conducted, he's very hopeful about the results, and thinks they signal a huge advance in treating indolent lymphomas like Follicular NHL.


As Press points out, Zevalin has been used up top this point as a "down the line" treatment -- when chemo stops working, you turn to RIT. It's been fairly successful when used this way.


However, a major new study looked at Zevalin as a first-line treatment. In other words, the study looked at people who were given Zevalin before they received any chemo or other treatments. The results were impressive: patients given either Zevalin by itself, or Zevalin combined with chemo, showed 90-100% response to the therapy, with up to 90% showing complete response (the lymphoma was wiped out, at least temporarily).

A second study that Press describes looked at using higher-than-normal doses of Zevalin after a shortened course of chemo (three doses instead of the usual six), and also came with encouraging results. The chemo wiped out a lot of the cancer cells, and the Zevalin took care of the rest. Combining the treatments means attacking in different ways, and increasing the chances that you'll hit more of the cancer.

This morning, I read about a third, similar study that looked at a patients with advanced follicular NHL (they were in the "bulky" stage, meaning their nodes were more than 10 centimeters, or about three inches), who were given a shortened course of chemo, followed by Zevalin, then followed by Rituxin. Similarly good results -- nearly 90% of patients were still in remission after two years. The study is ongoing.

It's all very encouraging, not just for the results themselves, but because they should inspire more people to try Zevalin (or Bexxar) and encourage researchers to keep tinkering with dosages, sequences, and follow-ups. I'm convinced RadioImmunoTherapy is going to play a bigger role in treatments soon, and we (the NHL community) are all going to be happy we gave it a chance.

Betalutin Update

The makers of Betalutin provided an update this week on their phase 2 clinical trial called PARADIGME. 

There wasn't much to report, which is I guess kind of the story. 

Some reminders about what Betalutin is:

Betalutin (also known as ¹⁷⁷Lu lilotomab satetraxetan) is a RadioImmunoTherapy (RIT) treatment being developed in Norway. RIT is kind of an exciting treatment, in my opinion. In general, RIT works by bringing radiation directly to lymphoma cells. Radiation can be very effective in treating cancer, though it works a lot better on solid tumors than liquid tumors like those in blood cancers, since blood cancer cells don't stay still. RIT works by attaching a tiny bit of radiation to something like a Rituxan molecule. The Rituxan finds the CD20 protein on the surface of the lymphoma cell, attaches itself to the cell, and then delivers the tiny bit of radiation directly to the cell. In theory, it's a great system -- fewer side effects because the radiation is delivered right to the cancer cells.

There have already been two RIT treatments approved for Follicular Lymphoma, and that approval happened years ago -- Zevalin and Bexxar. I was personally very excited at the idea of Zevalin when I was first diagnosed, because I had heard from a few people who had been given Zevalin and had very long remissions from it (even longer than my now almost 14 years). 

There are still some stories in the news about Zevalin, but no longer about Bexxar -- it was discontinued by the manufacturer because so few people used it. 

And that's the problem with RIT, at least in the United States. Very few people use it, despite it helping so many people. 

The reasons don't have much to do with effectiveness or safety, both of which are very good for Zevalin. Instead, they have more to do with rules for how it gets used. Because it is radioactive, any doctors administering Zevalin have to go through a large amount of training before they can be approved. That means regular oncologists won't be able to give the treatment, though they can refer patients to specialists who can give it. But with few doctors who have had that training, and lots of other options available, most oncologists just try a different treatment that they themselves can give to the patient. There has also been some question about how doctors are reimbursed for the treatment, creating enough of a hassle to just not use it. 

It's really too bad. I think RIT can offer an alternative that could help a lot of people, if it were easier to get to patients.

So the press release about Betalutin pointed out a different problem -- Covid-19 has made it harder to recruit patients into the trial. Like many FL treatments, one of the side effects of RIT is lowered immunity. That's not so good while Covid is around, especially with the new variant. 

The good news is, they have managed to recruit 106 patients, which is great for a phase 2b trial (their goal is 120). And they announced last August that they had made some changes to the trial that had helped it. Last February, they released data that showed good effectiveness and safety, with 65% of Relapsed/Refractory FL patients in the trial having a response, including 30% Complete Response.

So I'm hoping things continue to go well for Betalutin. I have an emotional attachment to RIT, given how excited I was about it many years ago. But I do think, even with a a rational head, RIT is a good approach to dealing with FL, and gives a different way of dealing with the problem. One of the studies that I was excited about many years ago was one that used RIT as a salvage treatment. That is, patients were given R-CHOP and then followed up with Zevalin, which cleaned up any cancer cells that Rituxan and chemo didn't get to. That approach made sense to me then, and still does -- it's the basic idea behind the combination treatments that are so popular these days. Cancer cells find ways to stay alive, so going after them in different ways (chemo + antibodies + radiation; or antibodies + inhibitors; or chemo + CAR-T) may catch those cells that the other treatments missed.  

And maybe some success from a new RIT will inspire change in the way it is administered in the U.S. and allow more people to get it. I don't know what the rules are in Europe and elsewhere, but maybe they are different enough that it would be easier to administer there.

I'm hoping maybe we'll get another update by ASCO. I'm looking forward to hearing more.

April 2

I was going to post something yesterday, but I didn't want to either (1) have what I said be misconstrued as an April Fool's joke, or (2) have to come up with a really good April Fool's joke on my own, which I just don't have the energy or the time for these days.

So you'll just have to get a straight and serious news report from me instead.

I have been extoling the virtues of RadioImmunoTherapy for almost two years now, and more great news keeps coming in.

The latest is that Bexxar (one type of RIT, along with Zevalin) is safe when used a second time. There had been some speculation that Bexxar might have long-term negative effects on bone marrow that would be even greater if used more than once. However, this does not seem to be the case. (I can't get a link to the article to work, so you'll have to take my word for it.)

This is important because many doctors are reluctant to try RIT on their patients, and those who are willing will sometimes hold off on using it until other treatments have failed, because they think it can't be used more than once.

This is unfortunate, because research shows that RIT is more effective for lots of patients when it is used early on in the course of treatment.

There's a very nice review of RIT and its effectiveness on Follicular NHL from the January issue of Community Oncology, called "Radioimmunotherapy: A promising treatment strategy for follicular lymphoma." It includes a nice summary of recent research on how well RIT works, including studies that show it works well early on, and in combination with more traditional chemotherapies.

No joke.

RIT for FL: Betalutin

I've been talking about Betalutin for a few months now -- since the ASH conference, I think -- so I suppose it's time I wrote about it, huh?

It's especially timely since we've seen good news with RadioIummnoTherapy (RIT) in the last couple of months, too, with research showing that it is effective and safe.

Just as a reminder -- RIT is a type of radiation therapy. Conventional radiation therapy is effective on some types of solid tumors. Not so much on most blood cancers, where the cancer cells are floating around to much to shoot at them with a beam of radiation. RIT solves that problem -- it attaches a tiny bit of radiation to an antibody (something like Rituxan) that seeks out and attaches itself to a protein on the cancer cell (Rituxan attaches to CD20). The result is, ideally, the benefits of radiation without the side effects, since the radiation doesn't travel too far beyond the cancer cell.

Betalutin is, of course, another type of RIT.

There have already been a couple of other RIT treatments approved in the U.S. -- Zevalin, which is still around, and Bexxar, which is no longer being made. (Why? More on that below.)

Betalutin in a little different from other RIT treatments. It stays in the body a little bit longer, so it can kill off more cells, and the radiation it releases doesn't travel as far, so it should spare more healthy cells nearby. Most importantly, Betalutin targets CD37, rather than CD20. So for patients who are refractory to Rituxan (that is, it has stopped working for them), Betalutin could be a more effective option.

Someone sent me a link for a really nice video explaining how Betalutin works. Watch it here.

Researchers presented data for Betalutin at ASH in December. In the phase I/II trial, 61 patients were given straight Lilotomab (the monoclonal antibody that targets CD37), and then Betalutin (Lilotomab plus the bits of radiation). The study has 4 different arms, with patients receiving different doses to test which one works best (this is common in early trials). One arm seems particularly effective for Follicualr Lymphoma patients, with 81% of the 21 FL patients showing a Response, 28% of them showing a Complete Response. (You can look at the ASH abstract link for more details of the study, including safety issues, which were pretty good.)

Updated data were presented at the ASH meeting (you can see some of the numbers here).

As always, there are a couple of things worth mentioning.

First, this is an early trial. Approval in the U.S. would not happen for a while, assuming a phase III trial goes as well. Given that the makers of Betalutin are targeting patients who are refractory to Rituxan, it seems like they have a good target population that needs treatments. But it will be a while before this is available.

Second, and maybe more important, is that RIT faces some barriers in the U.S. The rules for handling radioactive treatments are strict -- it cuts down on the number of doctors who can administer it. It's a big reason why Bexxar could never get a grip, and why Zevalin is so under-used, despite its effectiveness. The video I linked above does mention that Betalutin comes in a ready-to-use formulation. I don't know if that makes it easier to administer, or if those same limitations will apply.

(You might remember Lymphomation made an effort to advocate for lymphoma patients by getting Congress to change those rules. It's never too late to get in touch with members of Congress to educate them about our disease and its treatments.)

So, bottom line is, in my opinion, Betalutin could end up being an effective treatment option for FL patients who are refractory to Rituxan. And you know I'm always in favor of having more options for us. This could be especially true for patients in Europe and other parts of the world where there is more enthusiasm for RIT.

As for the U.S., it's going to be a tougher road, but not a completely closed one. Just bumpier.

Best Treatment Plan for Follicular NHL?

All right, the whole First Rituxan Infusion thing went well, but it's time to get back to work.


If you're new to Lympho Bob, or you've started reading again after an absence, then you should know that I'm a cancer research geek, and I like to provide links to new lymphoma research here. Family and friends seem to like to hear about new developments, because it gives them hope, and my fellow fNHLers who have found the blog seem to like being up-to-date on potential options.


I get these links from a couple of Facebook groups, from postings to my support group, and through my own research. Recently, someone in the support group posted an article from the journal The Oncologist from a year or so ago, called "Radiolabeled and Native Antibodies and the Prospect of Cure of Follicular Lymphoma." The full article is available here.


It's on the technical side, written for oncologists, but it was worth wading through. The article is a review of research on fNHL, looking especially at Rituxan and RadioImmunoTherapy (RIT -- Zevalin and Bexxar); those are the Radiolabeled (RIT) and Native (Rituxan) antibodies mentioned in the title. The basic conclusion of the article is that a combination of Rituxan (or some other native antibody), Zevalin or Bexxar, and some chemotherapy is probably the best currently available way to treat Follicular NHL. The big HOWEVER here is that the authors are speculating, based on previous research -- this isn't a report of new research. It amounts to a kind of "best practices" summary.

Rituxan, they say, has done wonders for the treatment of fNHL (which we already knew). And RIT has also been fantastic. What's great is that they work in two different ways. Combine either of them with chemo, which works in a third different way, and the results are even better. So maybe combining all three together in some way (Rituxan with the chemo, then conditioning with Rituxan before RIT) might the best shot we have at a cure, or at least a long-term remission for fNHL.


More importantly, both native antibodies and radiolabeled antibodies could fairly easily be improved. Rituxan is great, but fully-humanized antibodies (no more mouse fantasies!), or antibodies that target proteins besides CD-20, might mean even greater success. And RIT could be improved by playing with the ways the radioactivity is released (that's the real technical part of the article) and then giving repeat applications of it. Combine those improvements with chemo, and you have an even better chance at cure/long-term remission.

Or so they speculate.

A very interesting idea, and one that doesn't even consider the ways other improvements might help (like genetic testing helping to determine which of the chemo options might be best). Certainly something worth considering for an fNHL patient who is taking Rituxan and might be moving on the CVP, and who has an obsession with radiolabeled antibodies.....

RCHOP + RIT + Rituxan Maintenance in FL

There was a lot of comment a few weeks ago when I wrote about CHOP vs RIT, so I thought I'd add more to that conversation.

A couple of weeks ago, The Lancet Haematology released the article "R-CHOP, Radioimmunotherapy, and Maintenance Rituximab in Untreated Follicular Lymphoma (SWOG S0801): A Single-arm, Phase 2, Multicentre Study."

This study is a little different from the one I wrote about last month. That study was a much longer follow up, and compared CHOP + Maintenance to CHOP + RIT + Maintenance.

This study from Lancet Haematology is a single-arm study -- it isn't comparing two treatments directly, but instead looks at just one group of patients. It also looks at a much shorter follow-up period (just 3 years).

Still, it has some interesting things to say.

The participants were Follicular Lymphoma patients who had not had any treatment. They were given R-CHOP for 6 cycles, followed by RadioImmunoTherapy within 12 weeks after the last CHOP dose (in this case, the RIT was ¹³¹iodine tositumomab, or Bexxar), and then up to 4 years of Rituxan Maintenance (every 3 months).

The results were about what we expect from RIT -- Progression Free Survival at 3 years was 90%.

The researchers' interpretation of the results is where it gets interesting. They say there was "near universal responses" from the R-CHOP and RIT. However, 84 patients signed up for the trial, 73 completed the R-CHOP and RIT, 69 registered for the maintenance, and only 41 completed all 4 years.

That's a big drop. The researchers note that most of the people dropping out the study did so during the maintenance phase, and suggest that 4 years might be too long for a lot of patients. (Standard length for maintenance is usually 2 years, though that can vary for different patients.)

There was a decent list of side effects from this treatment as well, mostly related to nerve issues and blood count drops (which are fairly typical for these treatments). But there were also 7 cases of patients developing another cancer in that 3 years, with 4 of them resulting in death, with 9 patients overall with "possible treatment-related deaths" (it's hard to know for sure, for example,  if the patient who died from cardiac arrest had that result from CHOP, which can cause heart damage).

This seems, at first, like bad news for Rituxan Maintenance (which is still kind of controversial). I think, though, that it says something about extra long Maintenance, rather than Maintenance in general. And it's worth pointing out that, even though a lot of patients didn't complete the full 4 years of Maintenance, it's possible that not all of them did so for health reasons -- some might just not have been able to commit to 4 years of doctor's appointments, or got good news after 2 years and decided that was plenty. So 4 years might be too long, but it could be for a bunch of reasons.

As for the RIT, this strikes me as more evidence that it works. (This is a good time to remind you all that I'm not a doctor or a cancer researcher, just a patient who reads a lot.) It fits with other studies of CHOP + RIT, in terms of PFS and side effects (secondary cancers have been reported with other studies of RIT as well).

Like with the other study from a few weeks ago, it frustrates me that a treatment that seems to work so well is not used more. There is a newer RIT treatment being tested in Europe called Betalutin that has shown some success in trials. One trial protocol suggests that it could be tested in clinical trials in the U.S., but I'm not sure anyone has enrolled yet. I'm looking into that a little more -- maybe I'll write about it soon. (I have a bunch of other posts already on my list.)

So, perhaps mixed results from this one, but still some good news, and worth looking to see if it goes to a phase III trial (which would be hard, since Bexxar isn't available anymore) or there is a longer-term follow up.