Two Excellent R-Squared Studies for Follicular Lymphoma

It seems to me that the combination treatment that has gotten the most excitement from researchers in the last 5 years has been R-squared -- Rituxan + Revlimid (also known as Lenalidomide). Even when research results seem kind of mediocre to me, researchers comment on how great R-Squared is.

And now there are a couple more reasons for them to be excited. Both came from research that was presented this month at the 2017 International Conference on Malignant Lymphoma in Luagano, Switzerland.

The first study looked at R-Squared in Follicular Lymphoma patients who had not had any previous treatments. Results were excellent, with 95% of the 66 patients getting a response, and 72% of them getting a Complete Response. More importantly, The 5 year Progression Free Survival rate was 70%.

Seems like something that worth getting excited about.

The other study looked at a different population -- FL patients who had been heavily treated, with some of the 160 Follicular Lymphoma patients in the study having already received up to 9 previous treatments.

2017 International Conference on Malignant Lymphoma210

For this study, patients received R-Squared, and were then given maintenance of either straight Rituxan, or more R-Squared.

Results were, again, very strong, especially since this group was either double refractory to immunochemotherapy (both Rituxan and traditional chemo had stopped working), or had "high risk" FL, or had relapsed early (within 2 years after diagnosis and first treatment).

Of the 50 FL patients who were double refractory, the Overall Response was 45%, with a 21% Complete Response rate. The 1 year PFS for this group was 65%.

Of the 52 FL patients who relapsed early, the Overall Response was 47%, also with a 21% Complete Response rate. The 1 year PFS for this group was 49%.

Of the 60 FL patients who were considered High Risk, the Overall Response was 66%, and the 1 year PFS for this group was 70%.

This second study was a phase III clinical trial, which means it could be ready for FDA approval soon.

It is worth noting that, for all the excitement R-Square creates, it has not been approved yet by the FDA for any Follicular Lymphoma patients. there have been concerns about Lenalidomide/Revlimid's toxicity for a while. In this second study, there were several side effects, including several types of low white blood cell counts that could lead to higher risk of infection, fever, and blood clots. 

But overall, these studies seem to add to the happy feelings that lymphoma researchers have about the combination.  Another arrow in the quiver -- perhaps soon.

[Note: I usually give links to the conference abstracts for something like this, but I'm having trouble accessing them, so you're getting links to reports about them instead.]

The 1-year progression-free survival (PFS) rate was 70% with rituximab and lenalidomide. In the double refractory and early relapse groups, the 1-year PFS rates were 65% and 49%, respectively. In the early relapse group, the 1-year PFS was similar in those who received frontline rituximab/chemotherapy (n = 39; 52%) and those received a non-rituximab chemotherapy regimen (n = 13; 44%). In high-risk patients, the 1-year PFS rate was 70%.

The 1-year progression-free survival (PFS) rate was 70% with rituximab and lenalidomide. In the double refractory and early relapse groups, the 1-year PFS rates were 65% and 49%, respectively. In the early relapse group, the 1-year PFS was similar in those who received frontline rituximab/chemotherapy (n = 39; 52%) and those received a non-rituximab chemotherapy regimen (n = 13; 44%). In high-risk patients, the 1-year PFS rate was 70%

CAR-T Videos

There's a whole lot of really good stuff coming out of three important meetings for blood cancer specialists this month. I've already written a lot about presentations at ASCO, and there are also two great meetings happening in Europe.

Unfortunately, I'm in the middle of dealing with a small flood in my basement, and I haven't been able to read and write as much as I'd like, so I'm going to give you a couple of videos instead.

I'm seeing lots of very excited oncologists talk about all of this on Twitter, and I have to say, the thing that is generating the most excitement is CAR-T. Early results are excellent, and updated results are still very strong.

The first video is a long one (about 17 minutes), and features Prof. Stephen Schuster, a lead researcher on CAR-T. He explains in a lot of detail how CAR-T works, if you're looking for a fairly easy-to-understand summary.  The link comes from the blog CAR-T and Follicular Non-Hodgkin's Lymphoma, which features updated links to research and commentary about CAR-T. It's put together by Ben, an FL patient who had great success with CAR-T, and Will, whose wife also has had success with the treatment. Both of them are regular commenters here. If you're looking for an excellent source of information about CAR-T and FL, that's the place to go.

The second video present some of the same information as Dr. Schuster's, but in much shorter form. It features Dr. Jeremy Slade Abramson, who has done some research on CAR-T as well.

It's easy to see whay lymphoma researchers are so excited about this treatment.

Enjoy. I'll get back to some more of the good news about Follicular Lymphoma soon.

Good News for Transformation in FL?

We barely get to catch our breath from ASCO, and we now we have the International Conference on Malignant Lymphoma in Lugano, Switzerland. Lots of good stuff coming out of there for Follicular Lymphoma.

One of those presentations is called "The Risk of Trasformation of Follicular Lymphoma "Transformed" by Rituximab: The ARISTOTLE Study Promoted by the European Lymphoma Institute."

As the title suggests, this very large study showed a much smaller risk of Transformation than previous studies, and it gives the credit to Rituxan (Rituximab/Mabthera).

I assume most of you know what "Transformation" is, since it always seems to be tucked away in our minds somewhere, ready to jump out and scare us when we have a fever or notice a new bump somewhere. But here's a reminder anyway. Follicular Lymphoma is, as a specialist told me long ago, a "genetically unstable" disease. If we are lucky, it take an indolent course, growing slowly and not interfering too much in our lives. But sometimes, it transforms -- it turns into a different kind of cancer, one that is more aggressive. (It usually turns into Diffuse Large B Cell Lymphoma, but it can become other types, too.)

Transformed FL needs to be caught and treated early -- better results come that way. There have been some improvements in the last few years in treating Transformed FL, but it's still a scary idea for most of us. And what makes it scarier is that it seems so common, if you believe the numbers. I have seen some statistics that say up to 50% of FL patients will transform. I've also seen some that say 35%, 30% or 20%. Different studies seem to give us different figures. The good news is that in the 9 years I've been paying attention, the numbers have been trending down. The most recent I have seen say that somewhere between 15% and 20% of FL patients will transform.

That's what makes this study so remarkable. The numbers are sliced up in different ways, but they all show that rate of transformation is under 10%.

This was a retrospective study -- it looks back at patients who were diagnosed with FL between 1997 and 2013. It looked at 7342 patients -- a VERY large number. It defined transformation as the first event after initial therapy; transformation had to be the first reason the patient needed a second treatment. The median time to transformation was 19 months.

Here are the numbers:
The 5 year risk of transformation was 5.5%.
The 10 year risk was 7.2%.

For patients who had Rituxan as part of their treatment, the 10 year risk was 6.2%. For those who didn't have Rituxan, it was 9%.

Breaking it down a little more, for those who did have Rituxan, the 10 year risk was 6% if they only had Rituxan as part of their initial treatment. It was 3.8% if they also had Rituxan Maintenance.

Those are darn good numbers all around, whatever the treatment was. All under 10%, which is a whole lot better than what we've seen, We should be happy about this -- and maybe just a little less worried as patients.

HOWEVER.....

You'll notice the question mark in my title. I do think it's good news, but as a patient, I still have some questions.

One of the things that the researchers point out in the abstract is that the statistics for transformation are hard to pin down because they are really hard to compare to one another. As they say, "the incidence of HT have wavered over the past several decades, due to the adoption of different diagnostic methods, definition of transformation, duration of follow-up, and type of treatment." In other words, the studies are different enough from one another that it's hard to say that the numbers from transformation are getting better because the studies might now be comparing the same things.

In this study, for example, transformation is defined as only the first event after initial therapy. As I read it, that means anyone who watched and waited, and then transformed before they were treated, would not be included here. And anyone who had a second treatment, and then transformed, would also not be included here. So if we're looking for an overall picture of how many transform, then this might not be accurate.

Another important issue that I have seen mentioned in discussing this study -- there is not any connection yet to clinical practice. In other words, don't think that Rituxan Maintenance will keep you from transforming. The researchers don't make that conclusion; they make the broader point that Rituxan (in whatever form) seems to have a positive effect on transformation.

So follow their lead. Worry just a little less about transforming. It might not really be 3.8% or 6%, but it's got to be a lot closer to them than to 50%. And that's pretty nice.

ASCO: R-B vs R-CHOP

One more from ASCO: a long-term follow-up of a study of Bendamustine + Rituxan vs. CHOP + Rituxan for indolent NHL patients. The B-R patients did better in almost all measures.

(Let's be clear here -- this study looks at indolent NHL, so Follicular Lymphoma is included, but the results aren't just about FL, and the abstract doesn't separate them out.)

The really important part of this study (known as the StiL NHL 1 Study) is that it compares the two treatments over 9 years. The researchers reported on the results of this study at the 5 year mark, and now they are showing updated results, with estimates for 10 years.

One important point -- the Overall Survival rate for both treatments is just about the same, at least by statistical measures. The estimated 10 year survival for the B-R group was 71%, and for CHOP is was 66%. A small difference, but not a statistical difference. Taking one over the other won't result in (statistically) living longer.

But for other measures, Bendamustine came out on top.


The median Time to Next Treatment (TTNT) was 56 months (almost 5 years) for the CHOP group, but the median hadn't yet been reached for the Bendamustine group. (The median is the number right in the middle -- half are more and half are less. So less half of the patients in the Bendamustine group had received a second treatment.)

The Bendamustine patients also had fewer second-line treatments (which makes sense, given the TTNT) -- 32%, while 51% of CHOP patients received a second treatment.

As for side effects, one measure is secondary malignancies -- how many patients developed a new cancer. Bendamustine does a little better there, too -- 36 patients, while 39 CHOP patients developed secondary malignancies.

For me (and my non-expert opinion), it seems like R-Bendamustine is a very good choice. (It really didn't take an expert to see that.) It's great to see long-term results that back up the short-term results.

But at the same time, it's important to remember that R-CHOP absolutely has a place in our treatment plan. My oncologist had planned to save CHOP in case of transformation, and that's still the way I think of it, given the fairly indolent course that my Follicular Lymphoma has taken. I know lots of folks who have had CHOP as a first-line treatment, and that's great, too. The point is, it's a still an excellent tool for us all.

It makes me wonder what long-term results will look like for some other exciting treatments, too.

I'm looking forward to seeing those.

ASCO: The Emotional Psychology of Cancer

As I said in the last post, there were some non-Follicular Lymphoma sessions at ASCO that I thought were really interesting. At least three talked about studies that looked at ways to reduce cancer patients' fears.

I said it last time, and I'll keep saying it -- Follicular Lymphoma is as much an emotional disease as a physical disease. Emotions play a huge role in an cancer type, for any cancer patient. But Follicular Lymphoma can be just a little different. For a lot of us, we don't have any physical symptoms. All we have are the emotional ones. Like fear that we are missing the physical ones. Worry that our watching and waiting is making things worse. Even guilt that we might not be dealing with a cancer that is as bad as some others. There's a lot going on in our heads and our hearts, and it's easy for doctors and others to assume that a lack of physical symptoms means there's a lack of emotional ones, too.

There were (at least) three sessions that looked at cancer patients' emotional psychology, and used rigorous scientific study to find ways to reduce their negative emotions.

The first looked at The Conquer Fear study. Conquer Fear is the name of a program that tried to teach cancer patients to reduce their Fear of Recurrence -- fear that their cancer would come back. It use techniques like attention training and detached mindfulness to get patients to be less afraid of their cancer coming back. The study had some patients use the Conquer Fear methods and others use relaxation techniques. The Conquer Fear patients had less anxiety about recurrence.

A second presentation described the CALM study. In this study, cancer patients had individual sessions over 3-6 months that had them explore things like communication with their health care providers, changes in themselves and their relationships, their sense of meaning and purpose, and their sense of mortality.This study, too, had a control group, but this one didn't get any emotional training. The CALM intervention patients showed less fear and greater ability to adapt.

A third presentation discussed something called STREAM, a web-based stress management tool for patients who were newly diagnosed. Patients would write online about their stress and receive feedback (also online) from a psychologist. Again, the group getting the intervention was compared to a group that did not get it. And again, those getting the intervention showed more positive ways of dealing with their cancer.

I don't think it matters which of the three studies did the best job. They all did different things, with slightly different groups of cancer patients.

The important thing is that they were all successful, and they all taught a similar lesson -- finding a way to work with your negative emotions is so very important for cancer patients. And that's true at whatever stage of this journey we are on.

And it's especially important for those of us with Follicular Lymphoma. We are told that, for most of us, our disease is incurable. That has to add a whole different layer of anxiety for us -- it certainly does for me.

I've told my story many times, but I'll give you a short version. When I was diagnosed, things were a whirlwind for a week or two. When they finally slowed down, I went into a deep, dark place. I was worried about my wife and small children. I'd break into tears every half hour or so. And I kept it all inside. When I finally started talking to my wife, things got better. And when I found a support group online, and could share with people who knew what I was going through, it got better still.

Recognize the emotional part of our disease. Find ways to deal with those symptoms, just as you would find ways to deal with the physical ones.

And if no one else seems to understand, feel free to write to me. I'm happy to listen.

ASCO: Symptom Monitoring

Well, ASCO is over now, which means pharma companies, universities, and other folks will be sending out press releases to  brag about their big successes at the conference. (And some of them are big success -- some really great news about prostate cancer that I'm seeing online.)

Unfortunately, there were no big blockbuster presentations about Follicular Lymphoma this year. Certainly some good news -- which I have been writing about, and will write a little more about soon. But nothing that has people outside of the Lymphoma community getting all crazy about.

But there were a few sessions that I have seen get discussed online that seem like they could have some implications for Follicular Lymphoma patients, and I want to share my thoughts about them.

The first one has to do with symptoms monitoring.

In this study, patients with advanced cancers were given access to an online program that would let them report any new symptoms. They were asked to report once a week, though they could report things sooner than that if they had problems. Nurses would check the program and provide advice to the patient, sometimes offering an intervention that would help if it was a normal, expected symptom, and sometimes having the patient report to the office as soon as possible, if the symptom seemed abnormal, or a potential sign of the cancer getting worse.

The study involved 776 patients at Sloan Kettering in New York. Researchers found that patients who used this online system extended their survival by about 6 months. That's longer than some actual treatments are found to help. Patients were also able to stay on a treatment for longer than they might have been, because nurses were better aware of their side effects and could help them deal with them more quickly.

The lead researcher on the study appeared in a video at ASCO to explain more about the how it worked.

I can't help thinking about how this would affect Follicular Lymphoma patients.

Many of us are able to watch and wait before we need treatment. Many more able to do the same after treatment. A key part of watching and waiting is looking for symptoms. And for many of us who have an indolent form of FL, growing slowly, we can go a while between oncologists' visits -- 3 months, 6 months, up to a year. If we are in the mindset that things don't need to be reported because we are months away from a visit, we might be more willing to overlook things.

That situation I described is where I am at right now, almost 10 years out since my diagnosis. But I can think of a couple of other situations where a tool like this might be helpful, with some variations.

For patients who are actively going through treatment, reporting side effects would be great, as was mentioned in the study. But also reporting other symptoms, like new swollen nodes, would help alert doctors that treatment needed to change to something more aggressive. (I like to think patients would do that even without an online tool, but I also know patients can sometimes be a little hesitant to "bother" a doctor, and maybe the tool would give them permission to do so.)

The other way this could be helpful would be with fairly new patients. I think back to when I was first diagnosed, and began watching and waiting. Every little bump, every bruise, every ache -- I thought all of it was a sign that my symptoms were getting worse. None of them really were. (I remembering cutting a vacation short because of a sharp pain in my upper leg. I panicked my entire family for what was really just a running injury.) I could see patients in the early stages after diagnosis using that tool and getting reassurance that they were OK.

But that would require something extra from the doctor's office -- some real understanding of the psychology of Follicular Lymphoma patients, which I believe is just a little different from other cancer patients. I've said it lots of times here, and I'll say it again -- Follicular Lymphoma is an emotional disease as much as a physical disease, and doctors need to recognize that.

So if someone newly diagnosed with Follicular Lymphoma, and on watch and wait, was to use this tool, I would hope that the nurses and doctors checking on it would be extra patient with us. They would need to understand that people who hold off on treatment are doubling up on their worries, and act accordingly -- calming our fears and taking our concerns seriously.

(The great majority of oncology nurses and doctors that I have met would do this. But I could see some offices not suing it because of the "extra work" it might bring on. And it would be worth emphasizing those emotional issues in any training that they might receive.)

It would be great if this tool became available for all cancer patients. But even if it doesn't, there's a lesson we can all learn:

Talk to your doctors. Tell them what's going on. 80% of symptoms are found by patients. Not doctors, not blood tests, not scans. But the patients themselves. Even if you don't have a cool online program to help, talk to your doctor.

(Not that I needed to remind any of you about that......)

National Cancer Survivors Day

Happy National Cancer Survivors Day!

In the U.S., today we celebrate cancer survivors -- and that mans anyone who has ever heard the words "You have cancer," and is still around today.

On my diagnosiversary every year in January, I always like to do something a little special -- skip work and go to a movie with my wife, take a long walk, bake a cake. And my wife, every year, tells me that it's a little strange to celebrate the day. And every year, I remind her that we're not celebrating the day I was diagnosed, we're celebrating every day since then.

And that's what Cancer Survivors Day is all about. It's a celebration of life.

And for me, that means 3,429 days worth celebrating.

Enjoy the day. Celebrate life.