Trouble for R Squared?

The big Follicular Lymphoma news from the past week or so has been the report from the phase III RELEVANCE trial, which looked at R-squared (Rituxan + Revlimid/Lenalidomide), plus R-squared maintenance) and compared it to Rituxan + chemo (CHOP, CVP, or Bendamustine) plus Rituxan Maintenance. The patients in this trial did not have any previous treatments for FL.

This is the first trial to do a direct comparison between FL patients who are getting traditional chemotherapy and patients who are getting a treatment that does not include chemo.

The first reports find that the R-squared was not superior to the chemo. There was no difference in Progression Free Survival -- the R-Squared did not extend the time that it took for patients' FL to get worse. There was also no difference in the percentage of patients who had a response.

The reactions to this have been kind of mixed -- and kind of fascinating.

A lot of the reports that I had seen about this are from business websites (like this one). The company that  makes Revlimid/Lenalidomide is one of the sponsors of the RELEVANCE trial, and made the announcement. Their stock price fell and their outlook was downgraded. Basically, investors think they aren't going to make as much money off of Lenalidomide as they had hoped.

But the medical and oncology websites are more hopeful (like this one -- OncLive is always great about exploring things from lots of different sides). So while there is some disappointment about the results, there is a lot of positive that is coming from it, too.

The lead researcher for the trial, Dr. Gilles Salles, said "This is the first phase III trial to evaluate a chemotherapy-free regimen to the established standard of care in patients with previously untreated follicular lymphoma and represents a landmark study in this disease setting. We look forward to further analyzing and presenting these important data at a future medical congress."


So that's the first positive here. For all of the talk of the future of treatment being chemo-free, this is the first trial that has actually done a direct comparison. Half of the patients got R-squared and half got R + chemo.  Other trials look at non-chemo treatments, but they compare them to previous trials that are already finished. This one took the same group of patients, making sure they are easier to compare, and divided them up. That's important. Direct comparisons are the best way of testing treatments.

But the other important thing that Dr. Salles said was that they will continue to analyze the data and will present it at future conferences. This was just the initial look at the numbers.

What else will they look for? Dr. John Leonard is quoted in the OncLive article: “Follicular lymphoma patients frequently choose less effective treatments—like rituximab alone versus rituximab/chemo—based on perceived quality of life advantage. R2 might be a choice made by some patients, even if less effective. The details of efficacy, toxicity, and qualify of life are key here.”

In other words, maybe the R-squared won't be as effective as the chemo, but it has fewer or less harsh side effects, making it possible to live a more normal life. Quality of Life is a big issue for Dr. Leonard, who recognizes that many of us could be living with FL for a very long time. What makes a treatment "effective" isn't just that it has met an endpoint like OS or PFS or CR, but that it helps us live our lives -- on our own terms, whatever they may be.

And so, I added the question mark to the title of this post. Is there trouble for R-Squared? Yes, in some ways, since it didn't do what it was hoping to do. But that doesn't necessarily mean it's a failure, and it doesn't necessarily mean it won't be approved.

It's also important to keep in mind that the RELEVANCE trial is for R-squared in untreated patients. Another trial, the MAGNIFY trial, is looking at R-squared in FL patients who have already had at least one treatment. They received R-Squared, and then maintenance with either R-Squared or just Rituxan. Unlike the RELEVANCE trial, the MAGNIFY trial did not do a direct comparison with another treatment.

And then there's the AUGMENT trial, which does do a direct comparison -- R-Squared versus Rituxan alone -- for patients who have had at least one treatment.

Both of those other trials seem to be doing well. So R-Squared isn't going away completely.

But it will be interesting to see how the RELEVANCE trial is analyzed, and what the reaction to it will be when the results are presented (maybe at ASCO or Lugano next spring/summer?). Just how important will Quality of Life end up being in the analysis?

Stay tuned.

Merry Christmas

I want to wish a Merry Christmas to all of you who celebrate the holiday.

And if you don't, I wish you a joyful day all the same.

Two years ago, I sent a wish for some inner peace for all of us. We could all use it -- not just at this time of year, but all the time.

Last year, I wished us some outer peace. We lived in a world way back then (a whole year ago) where there was so much that divided us. I'm not sure it's much better a year later. So I hope we can all do just a little bit this year to try to understand others, especially the ones that we disagree with.

I was trying to think of a Christmas wish for this year. It feels like I should be wishing for more of the same. We could all still use some peace.

On Saturday, I heard some good news. Someone I love will get the opportunity for a new beginning. And I started to think about some other people I know who could use a new beginning, too. It turns out there are lots of them.

So while I hope everyone finds some peace, I also know that finding peace sometimes means accepting the situation you find yourself in. And that's important.

But a new beginning is different. It means changing your situation.

For those of us with Follicular Lymphoma, acceptance is a big deal. Inner peace means we have wrapped our heads around the idea that we might be in this situation for a while.

But sometimes that can also mean that we wait for the next thing to happen.  Usually the next bad thing to happen. It's hard to start over when you're just waiting.

I can remember, early on after my diagnosis, having an opportunity come up at work, and turning it down, thinking "If I'm in the middle of this thing, and I need to get treatment, I'll have to give it up and that will ruin it all." I did that a couple of times. And then one day I thought about it. Don't bother with the special project at work, because you might not be able to finish it. But then, maybe don't bother with some of the regular work stuff, because you might not be able to finish that, either. And then I started thinking about all of the stuff that I shouldn't bother doing because I might not be able to finish them. In the end, I found that I shouldn't bother getting out of bed, because I might not finish the day.

And I saw how ridiculous that was.

Peace can mean acceptance. But acceptance can mean giving up, and being at peace with that decision. And that isn't always a good thing.

So this is my wish this year, whether or not you celebrate Christmas. When you are ready, I hope you find a way to make a new beginning. However big or small.

Enjoy the day, everyone. And thanks, as always, for reading.

The Importance of Exercise for Lymphoma Patients

I'm still cleaning out my files of links from ASH, and getting around to the things I saved before ASH. I'm backed up a lot.

I found one item from October on how exercise helps cancer patients, and then another from ASH on how exercise helps Lymphoma patients specifically.

The general cancer article from October discussed how good exercise is for cancer survivors. It reduces fatigue and improves physical function -- and "lean body mass to fat mass ratio," so we look better, too. They recommend "150 minutes of moderate or 75 minutes of vigorous aerobic activity per week, and 2 days per week of resistance training (e.g., with exercise bands or light weights)."

That shouldn't be too tough, right? Take a 30 minute walk 5 times a week. You even get to skip two days.

The Lymphoma research describes a session at ASH. It found that physical exercise may actually contribute to longer survival for lymphoma patients. Lymphoma survivors who increased their physical activity had a higher Overall Survival than those who decreased activity.  The researchers believe there should be more active attempts to encourage exercise in Lymphoma patients.

I recently looked back at some of my very early blog posts, and I saw how many of them involved running. I used to be a runner. Not so much any more. My knees aren't happy with me when I try. But I do try to get to the gym 3 days a week to work up a sweat, and I've tried to walk more (my phone helps me measure how many steps I have taken for the day, and I aim for 10,000, but I'm happy if I hit 8,000 on days when I can't be as active as I'd like).

I'm not going to claim that my being active has kept me alive this long. But I will say that I feel better and happier when I am being active. And I also think it's important to stress that it's really not too tough to get to that 150 minutes of moderate exercise each week.

But I also know that, for some of us, it's hard to be as active as we would like. It's worth talking to your doctor about what you can do to be active and get moving. If generally feeling better wasn't reason enough, then maybe the chance at a higher Overall Survival rate might be the incentive.

(One more thing -- one of the researchers for this study was Dr. Carrie Thompson. She was also the lead researcher on the Quality of Life study I wrote about a couple weeks ago. I'm happy that research like this is taking place. As much as I crave research reports that look at new treatments, I also know that we actually have to live our lives, day to day. I appreciate solid research that gives us some direction on how to extend our lives while we enjoy the time that we have. Dr. Thompson is quickly becoming one of those Lymphoma Rock Stars that I like to follow.)

Since we're coming so close to the beginning of a new year, when we traditionally resolve to make changes for the better, I hope you'll all think about small ways that you can be more active. Start slow -- no one is suggesting that you plan on running a marathon. But a 10 minute walk around the block after dinner would be a good place to start.

Atezolizumab Combo for Follicular Lymphoma

As I have said, now that ASH is over, I've been looking at the ASH follow-ups out there -- either commentaries on some of the FL research that was presented, or descriptions of some of the interesting research that I missed the first time around.

Here's another one that I missed -- a presentation on the combination of Atezolizumab (also known as Tecentriq), Obinutuzumab (also known as Gazyva), and Bendamustine (also known as Treanda).

Bendamustine has been well-known in the FL community for a while. It's a traditional chemotherapy that has been shown to be effective and well-tolerated. Obinutuzumab is a little newer. It's a monoclonal antibody that targets B cells (like Rituxan, which has been around much longer).

Atezolizumab is less well-known to people with FL, but it's better known to the wider cancer community. It was approved by the FDA in the last couple of years for certain types of kidney and lung cancer. Like Rituxan and Obinutuzumab, it is a monoclonal antibody. It works by targeting PD-L1, or Programmed Death Ligand 1. Just as Rituxan targets the CD20 protein on a cell's surface, Atezolizumab targets the PD-L1 protein. By blocking PD-L1, the immune system is able to send signals that the cancer cells are invaders and should be attacked.

According to the presentation at ASH, 42 FL patients were given the combination. 35 of those patients then had maintenance with Atezolizumab and Obinutuzumab. Most of the patients had not received treatment before.

The results were pretty good -- 85% Overall Response Rate, with 75% Complete and 10% partial. (The Response rates were calculated a few different ways; these numbers are the most conservative of them.)

There were, of course, side effects, with all 42 patients experience Adverse Effects of some kind (and over half of them experiencing grade 3 or 4, the highest AEs).

This combination  makes sense. There have been some attempts at using Atezolizumab on its own in Lymphoma, but they haven't been very successful. The three different treatments mean the cancer cells are being targeted in 3 different ways. An approach like that makes sense.

However, as we have seen in combination treatments, sometimes different treatments interact in ways that create problems that aren't there when they are used on their own. It seems like this combination has that potential. The lead researcher, Dr. Anas Younes, noted that long-term follow-up will be necessary to see if the risks of the combination is worth the results.

Dr. Younes describes the study in a video for OncLive. Definitely early, but something worth keeping an eye on.

CAR-T Follow-Up

Well, ASH is over, and that means it's time for the press releases from researchers and analyses from experts about what mattered most. I'll keep an eye on it and report back on the good stuff.

One of the outcomes from ASH that has gotten some attention was the updated numbers on CAR-T therapy.

If you've been reading the blog for a while, you are familiar with CAR-T, or Chimeric Antigen Receptor T cell therapy. It's a very recent, very promising treatment that involves removing T cells (a kind of immune cell that usually attacks invaders) from a patient, changing them in a way that makes them recognize cancer cells as invaders, putting them back into the patient, and allowing them to do their job. CAR-T has shown some real promise for Follicular Lymphoma.

You can read more about CAR-T from two readers, Ben and Bill, who run the CAR-T and Follicular Non-Hodgkin's Lymphoma blog. Bill sent me a couple of emails with links (thanks, Bill) -- for a presentation at ASH, and a publication in the New England Journal of Medicine, with updated data on CAR-T treatments in lymphoma, including Follicular Lymphoma. (Ben is a CAR-T patient, as is Bill's wife.)

The NEJM article looks at 111 patients with "refractory large B-cell lymphoma after the failure of conventional therapy." Basically, they haven't been able to get a response with the things they have tried. And that group of large B-cell Lymphoma patients includes patients with Transformed Follicular Lymphoma.

Of the 111 patients, 110 were able to have T cells changed, and 101 of them were able to have them administered.

The Overall Response Rate was 82%, with a Complete Response of 54%. With a Median Follow-Up of 15.4 months, 42% of patients who had a response continued to have one, and 40% of patients who had a Complete Response continued to have one.


Out of this larger group, 16 patients had Transformed Follicular Lymphoma. They were analyzed as part of a slightly larger group of 24 patients (the rest had another type of Lymphoma). In that group of 24, 20 of them had a Response (17 had a Complete Response), and 2 more had Stable Disease.

One of the concerns about CAR-T treatments are the side effects, which can be especially harsh. In the NEJM study, every patient had at least one adverse event. These included neurologic problems and Cytokine Release Syndrome, though they seemed to be controlled, and the treatments to control the symptoms did not seem to have an impact on the treatment. (I get the sense that CAR-T researchers are better prepared for these problems, though I don't want to downplay how serious they are.)

The most important thing to come out of the study is the treatment's durability -- it lasts a while. People who had a response right away continue to have a response.

It seems like CAR-T treatments remain as promising as we had hoped (so far). It will be interesting to see the next long-term follow-up to see if the responses remain as durable as they have been.

ASH Preview: Quality of Life

The ASH conference is going on this weekend, but I have one more preview. It's a presentation scheduled for tomorrow (Monday, Dec 11): "Changes in Quality of Life in Indolent Non-Hodgkin Lymphoma 3 Years after Diagnosis." Since it hasn't happened yet, it's still technically a preview.

I am indebted to Dr. John Leonard for pointing this one out to me. When I searched for ASH abstracts for FL, this one didn't show up, since it covers "indolent lymphomas," which, of course, includes Follicular.

Dr. Leonard is active on Twitter, and in the days leading up to ASH, he tweets "Leonard's List" -- the 10 presentations he is most excited about. This one is #1 on The List. His comment on Twitter when he named this one as his #1 was this (I'm translating a little bit from Twitter-ese -- I know many FL patients are on the older side, and this kind of this is difficult for you to understand):

Since a large percentage/most indolent NHL patients will live a normal lifespan, here Quality of Life is a key issue/goal in long-term management. The study has important insights for Quality of Life course, reassures patients that Quality of Life likely won't deteriorate despite diagnosis, and patients seem to have psycho-social adaptation.

(Actually, I know most of you could have figured it out, even at your age. I was more concerned with how it would translate for my non-English-speaking friends.)

I appreciate his giving the top spot on his influential list to something that focuses on Quality of Life. As much as we all appreciate research that moves toward a cure (or at least a longer Overall Survival), we need to live with the disease, and the quality of that life can be an afterthought.

So QOL becomes an important factor. There are two approaches to FL research these days. One school of thought says we should go for a cure. But the other approach is to treat FL like a chronic disease, something that will always be with us, but can be managed through medication. I personally am open to either approach. But if I am going to treat FL like a chronic disease, then whatever treatment I receive must take Quality of Life into account.. There's no point in staying alive as long as the general population if I'm going to be miserable doing it.

For this presentation, the researchers acknowledge that Quality of Life can be affected by the disease itself, by side effects from treatments, and from the "psychosocial effects of living with an incurable cancer." (I'll say it again -- Follicular Lymphoma is an emotional disease as much as a physical one.)

Patients with Indolent (slow-growing) Non-Hodgkins Lymphoma (including Follicular) were included in the study. Their QOL was measured at Baseline (from what I can tell, within 9 months of diagnosis) and then 3 years later. QOL was measured using a survey called Functional Assessment of Cancer Therapy-General scale (FACT-G). You can see the survey here. It asks patients to measure their responses to fairly simple statements in 4 areas: physical, social/family, emotional, and functional well-being. So statements for "emotional well-being," for example, include things like "I feel sad" and "I am losing hope in the fight against my illness." Patients respond with how they have felt in the last 7 days.They were also asked to complete a "a single item Linear Analogue Self-Assessment (LASA) for measuring overall QOL."

1050 patients were included in the research (32% of them had grade 1 or 2 FL). At the 3 year follow-up, 577 patients (55%) had received treatment, 42 (4%) transformed, and 53 had an event (progression of disease, re-treatment, or death).

Interesting results:
Emotional Well-being significantly improved over 3 years.
Social/family Well-being  significantly decreased.
Functional Well-being, physical Well-being, and overall Quality of Life were not significantly different. 
The results were similar whether patients got treatment, or they watched-and-waited. 

In patients with an event during the 3 years, emotional Well-being had a significant improvement, but overall QOL decreased.

In patients without an event, improvements were reported in functional Well-being, physical Well-being, emotional Well-being, and overall QOL, but social/family Well-being went down.  

In their conclusion, the researchers say that the increase in emotional Well-being is a sign of "psychosocial adaptation by the patient." In other words, we learn how to deal with it.

I think that's probably true. We don't have much choice to adapt, so we adapt. We are, on the whole, very strong people. Sure, we have our bad days, but we get out of bed and get stuff done. That's just the way it is.  

It's hard to think back to where I was 3 years after I was diagnosed. I was a year past Rituxan treatments. I think I felt pretty good. It always helps to get a pretty clean scan. I was still running, so my physical Well-being was great.  I had support from family and friends. My day-to-day life was OK -- I was still working and playing with my kids. It all matches up for me.

What I found kind of surprising (though as I think about it, it shouldn't be surprising) is that the Social/family Well-being went down. 

As I think about it, this, sadly, makes sense. I hear lots of stories from people whose relationships were changed by cancer. family and friends stopped calling, probably because they didn't know what to say. That happens a lot, no matter what kind of cancer.

But people with FL and other indolent blood cancers face a different set of challenges, I think. 

When we get a diagnosis, lots of people come to our side. They want to help. And then -- nothing happens. Many of us watch and wait. The heat from the diagnosis starts to die down. Some people might feel a little betrayed. That cancer diagnosis had everyone worried, and now you don't even need treatment? Even worse than the people who don't know what to say are the ones who went on the emotional roller coaster ride with you, and got off before the ride started up again.

Are think there are two big lessons here.

The first is for patients. For many of us, we learn how to deal with the emotions that come with the diagnosis. We are, as I said, a strong group of people. We find ways to deal with it, and we do our best. For some us, though, we don't get the social help that we'd like. The lesson is that it's really important to find a social outlet. If family and friends can't help, then some group that understands what you are going through is crucial. Maybe that's a support group at the hospital you are being treated at. Or an online group (which is what worked for me). A Facebook group. Some bunch of people who can hear what you have to say and respond with "Yeah, I felt that way, too." 

The second lesson is for doctors. The physical check-up should be easy. The emotional check-up doesn't always come with the office visit, but it's just as important. And maybe doctors aren't comfortable with that, or aren't trained in that. But having some kind of resources available at hand would be helpful. Just a quick, "How are you feeling, emotionally?" might bring great results. Sometimes just being asked is a wonderful thing.

But the biggest take-away here is that researchers are paying attention to Quality of Life. That's a great thing. Certainly worthy of being #1 on any list.

More on Rituxan Maintenance

I had planned on writing about something else today, but Mylegacy left a comment with questions last night on my last post. I put the comment off to the side and got back to writing, but the Cancer Nerd got the best of me and I started doing some research, and I found the whole thing fascinating, so I'm just going to answer it here.

At least, I'm going to try to answer it. This is a good time to remind everyone that I am not an oncologist or a cancer researcher or a biologist. I'm just a patient who reads a lot.

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Here is Mylegacy's comment:

What follows is/are a/several convoluted question(s). I do not know enough to say what follows as a statement of fact. IF I've missed the boat - PLEASE give me the smack down I'll deserve!

I understand that most of us who die with our "incurable" guest will do so from "infection." Most likely pneumonia or other respiratory illnesses. We will not succumb to FL, as such, but to the failure of our - by the time we're near dying - badly damaged white B cells being unable to guide the T cells to the pneumonia in great enough numbers, and in a short enough time frame, for our immune system to save us. Is what I have just written there correct(ish)?

IF SO: Then that is why I'm opposed to R maintenance. R is an indiscriminate killer of white B cells (is it not?). Cancer, or no cancer, R kills them. The ONLY reason it is safe(ish) is because it DOES NOT kill white B STEM cells. These "Baby B cell factories" continue to produce new B cells in our bone marrow.

However - over time IF you use R maintenance - who are reducing B cells and you end up with mostly new(ish) immature B cells. Our immune systems suffer - those of us who will die, will do so from the infections our mostly "baby/immature" B cells can not destroy. Our adult, mature, effective B cells have been decimated over time.

I've only had one 6 month R/B dance so far but just now (6 months after my final 2 day adventure) I'm in the 19th day of a cold. I'm 71, had a few colds in my time, but NEVER have I had one last this long. I'm beginning to think I understand what my future might look like. To make this journey even more interesting - I've already had pneumonia once about 15 years ago.

Intuitively, why wouldn't B maintenance (just killing Cancer cells) make more sense than reducing generations of adult B cells and diminish our bodies immune system being able to find and identify the bad guys for or T cells to kill? 

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OK, lots to respond to. (And it's just a response. I don't think I've given anyone a "smack down" since I was on the wrestling team in high school....)

We'll start with how we die -- that's the thing that caught my eye first.

I'm not a big fan of talking about death (I'm sure not too many of us are), though it's certainly in the back of our minds as cancer patients (and maybe the front).

I think the description of FL patients dying of infection is accurate for some patients, but I'm not sure I'd commit to "most" patients.

And before we go any farther, I want to remind everyone about what I wrote a couple of weeks ago about Overall Survival. Death is always part of the equation for cancer, but the median OS for FL patients is close to 20 years, and statistics don't say anything about individuals. Keep reminding yourself of that.

There has actually not been a lot of research on how FL patients die, though earlier in the year, there was a presentation at the Lugano Conference called "Cause of Death in Follicular Lymphoma in the Rituximab Era: A Pooled Analysis of French and US Cohorts." There were 1643 patients in the study, who were diagnosed from 2001 onward. The median OS for the patients was about 80% at 10 years.

The median follow-up for the patients was about 85 months, or about 7 years. In that time, the OS was about 83% -- 283 of 1643 patients had died.

(Let's repeat that, since we're talking about death here -- 83% of the FL patients in this study lived.)

Of those 283 patients, 49% of them died of Lymphoma. Another 15% died of treatment-related causes, including infection, heart problems, and Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) -- basically side effects of the treatment, whatever the treatment was. Another 12% developed and died from a different cancer, and a final 12% didn't have a cause of death listed for the study.

Of that 49% (about 140 of the 1643 patients) who died of Lymphoma, about 55% of them died from Transformed FL.

Now, even though "infection" is listed as part of that 15% treatment-related cause, Mylegacy's comment seems to be including "infection" in a broader way, one that would make it part of the "Lymphoma" cause. It certainly is the case that for some cancer patients, a weakened immune system leads to infection, including pneumonia. But that's not the case for everyone.

I think the important thing here is to understand that 1) Follicular Lymphoma doesn't kill everyone who has it -- it's a fairly small percentage, and 2) the cause of death varies.

That's important to make clear, given the second part of the comment.

Rituxan Maintenance does indeed kill mature B cells. But I don't think the immune system works in such a way that we end up with only immature B cells as our only defense. For one thing, not all B cells express CD20. And for those that do, not all of them are killed by Rituxan.

Stepping back a little -- Follicular Lymphoma is a B cell lymphoma. It affects a particular type of white blood cell called a B cell. B cells go through a a series of steps before they are "mature" -- able to do their job of finding invaders in the blood. If you want an explanation of how B cells develop, this video does a decent job of explaining. B cells start out in the bone marrow, and over time become differentiated -- the body sends signals that let the stem cell know which type of blood cells they need to develop into. So they develop into a form of B cell that is able to accept an antigen -- the thing that lets them fight a specific type of invader.

In the scenario described in the comment, Rituxan would wipe out all of those later-stage B cells that are able to accept an antigen, leaving only B cells that can't fight off invaders.

I don't think it works that way. Bone marrow produces new stem cells all the time. (I read somewhere that it is several million every day, but I can't find that source again.) Some of those cells will move on down the chain that eventually leads them to develop into mature B cells. The point is, the body has a supply of them ready to go when signals come that an invader needs to be fought. It's an ongoing process.

Rituxan goes after those B cells -- they have a protein on their surface called CD20 that Rituxan attaches to. It goes after them whether they are cancerous or not. That is certainly true. And while people are taking Rituxan, they are, for that reason, more susceptible to infection.Their B cell counts are lowered. But it's important to note that Rituxan doesn't wipe out the entire immune system. Some B cells remain in the blood, and stem cells go untouched, and they keep differentiating into B cells. 

The next question is, how long is the patient affected by this?

Well, Rituxan works slowly. It can take a couple of months for it to really start to bring the size of tumors down. And then Rituxan's effects can go for up to 6 months. It could be a full year before the immune system is back to "normal" again.

(By the way, I'm getting a  lot of what I'm giving here from the Lymphomation.org page on Rituxan. They're my go-to for all things Lymphoma-related.)

With Rituxan Maintenance, that period could extend for up to a year after the maintenance is finished (so if we're talking about the standard 2 year maintenance, then you'd have a good 3 years before the Rituxan's effects were finished.)

Next important question: are there any long-term negative effects from Rituxan?

Yes, for some patients. Again, Lymphomation.org helps us here, citing some studies that show that "Late Onset Neutropenia" is a side effect for 5% to 27% of patients who received Rituxan. For as much as a year after treatment, patients can have abnormally low levels of neutraphils, a type of white blood cell. I haven't seen anything to suggest that it's a chronic condition brought on by Rituxan. My understanding is that it is treatable.

So, again, the important point here is, Rituxan does a good job of taking out cancerous B cells, and does result in some side effects, including making patients more prone to infection. But those don't seem to be long-term. The idea that Rituxan Maintenance might have a negative effect on our immune systems over the long term just doesn't seem to be the case.

And further evidence about a lack of long-term side effects comes from the study that Mylegacy was commenting on. Both the maintenance group and the non-maintenance group in that study had about the same median Overall Survival rate -- about 80% after 10 years. If there was a negative long-term result from Ritiuxan Maintenance, I assume we would see a difference there, with a lower OS for the maintenance group.

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So let's sum all of this up.

Rituxan Maintenance is controversial. Given how it works -- finding and killing off B cells, whether they are cancerous or not, and lasting for up to a year -- it makes sense that it prolongs Progression Free Survival, when compared to patients who had a similar initial treatment but no Maintenance. 

However, while it does increase the risk for infection (given that it weakens the immune system), there does not seem to be a long-term negative affect. Patients who had maintenance after immunochemotherapy had the same Overall Survival rate as those who didn't have maintenance. The controversy comes when you ask whether the short-term risks are worth it, given the same long-term result in OS. Lots of different answers to that question.

Now, as far as causes of death, there's no question that infection (in some form) is a cause of death for some FL patients (as it is for other cancers). Many different treatments affect our immune systems -- including Rituxan.

But long term? The evidence that I found does not suggest that Rituxan or Rituxan Maintenance plays a role in long-term infections. If anything, experts agree that Rituxan has extended Overall Survival. Since the beginning of the "Rituxan Era" in the late 1990's, OS for Follicular Lymphoma has about doubled. 

And as for the last question in the comment -- why wouldn't Bendamustine Maintenance work better? Well, Bendamustine is a chemotherapy, and its side effects would probably cause much more damage through repeated use over the long term than Rituxan would. But the point is well-taken -- treatments that target the cancer cells, and not healthy cells as well, make a lot more sense.

And that's exactly what more recently-developed treatments are trying to do. We know so much more about the genetics of cancer cells now than we ever did, enough to know how to find particular biomarkers -- clues that let us know which cells need to be killed and which can be left alone, and which treatments can find distinguish between them. 

That's the future. And partly the present. Lots of treatments in different stages of development that will find cancer cells and get rid of them as needed. Researchers are still working on those.

But until that's all perfected, we could do a lot worse than Rituxan.

Thanks for the comment, Mylegacy. I hope that answered your questions. And I'll close out by saying, once again, that I'm not an oncologist or other expert in this area. I'm confident in the numbers I give, and what they have to say, but I know I oversimplified the biology. If anyone has a better explanation for all of this, please let us know.