FDA Approval for R-Squared

I know I promised ASCO stuff over a week ago (the conference started today). But there was some news today from the FDA that needs to be shared:

R-Squared has been approved for previously-treated Follicular Lymphoma (and Marginal Zone Lymphoma, but that's not the focus here).

R-Squared is, of course, a combination of Rituxan and Lenalidomide (also known as Revlimid). I've been reading about it for years, and seeing the excitement from researchers has been very cool.

It's always been a big deal because it's a non-chemotherapy option that works as well or better than chemo.

The approval comes from two clinical trials. The AUGMENT trial compared R-Squared with Rituxan. The median Progression-Free Survival for R2 was 39.4 months, with an 80% response rate, versus 14.1 months for Rituxan, with a 55% response rate.

The second trial was called MAGNIFY, and it did not have a direct comparison between R2 and another treatment. The response rate in this trial was 59%.

In the two trials combined, at least 20% of patients had side effects including neutropenia, fatigue, diarrhea, constipation, nausea, and cough. There is also a "Boxed Warning" (the most serious warning from the FDA) about the risk of embryo-fetal toxicity, hematologic toxicity, and venous and arterial thromboembolism, all of which could be fatal (but which are rare).

This approval is for patients who already had treatment. There is still the possibility that untreated patients might get R-Squared approval, too, based on the RELEVANCE trial. Still waiting for an application for FDA approval for untreated FL though there are some concerns to deal with before that happens.

But for now, this is excellent news. Another arrow in the quiver -- another option for FL patients.

Back to ASCO soon. The press releases for any Big News should be showing up starting tomorrow.

Milestones

My daughter graduated from high school yesterday. She's my youngest. My boys are 22 and 20, already in college.

When I was diagnosed, I didn't think I was going to see any of that.

My birthday comes in a couple of weeks. I'll be 52.

I wasn't sure I was going to see that, either.

It's hard to come to a milestone and not see it through the eyes of a cancer patient.

When I was diagnosed, I was 40 years old. My kids were 10, 8, and 6. I remember praying, Please give me five years. If they're 16, 14, and 12, maybe they'll be old enough to be OK. I went through my list of friends that I wanted to keep an eye on my sons. My wife could do plenty for my daughter, and she could take care of my sons, too. But I wanted someone who could be a role model for how to be a good man.

I remember, soon after I was diagnosed, thinking of an old friend who had married a wonderful woman, and who had gained a teenage son, whose own father had died when he was 11. The teenager was such a great kid. And I remembered that this teenager was getting social security checks until he turned 18 because he had a deceased parent. I can still feel the weight that was lifted off of me when I realized that my own kids might benefit from that, too, if something happened to me.


It's amazing to think about the kinds of things that go through our heads at a time like that. We imagine a future without us. (But without trying not to think too much about the details.)

And as we watch and wait, and get treatment, and do better, we move forward into that future. But we don't always look back. Better to live in the present than to think about what might have been.

(I'm arrogant enough that I don't want to imagine a world that doesn't have the joy of having me in it.)

I do think there's some value in looking back. It's always good to remember where you came from. Sometimes even looking back a few weeks is good. We should remind ourselves that we made it through difficult times, and we'll have the strength to make through the next difficult time, too.


But today, I'm looking to the future. My daughter will start college in September, at a school that she is very excited about. My oldest will graduate from college in September, and he's already looking to what will come next for him. My middle child has a couple of years left, but he's already finding his place and enjoying lots of success.

All of this means that my wife and I will be "empty nesters" in a few months (at least for parts of the year). And we're looking forward to that new part of our lives, too. My wife has been my rock since I was diagnosed (and before, of course). We're happy to see where life takes us next.

Lots of uncertainty, too -- with me, with my wife, with all of our kids. But we're used to that. Better to stay hopeful and be positive about it.

It's a good day.

ASCO: Most Effective First Treatment for FL?

ASCO Abstracts are here!

ASCO is the American Society of Clinical Oncology, an organization for cancer doctors who work directly with patients. Every year in late May/early June, they hold their annual conference. It's a big one, attended by thousands of people, so it's often where researchers and pharmaceutical companies will announce their big news, knowing it will get lots of attention.

A few weeks before the conference, ASCO published the abstracts of all of the presentations. It's an exciting time for cancer nerds, as we look through all of the summaries, trying to find the most interesting ones. And as I have been doing for a while, I want to share with you some of the things that are most exciting to me.

(To be clear -- it's the stuff that's exciting to ME. It's not necessarily the stuff that makes the news. So it's lots of Follicular Lymphoma research, of course, but also some general stuff about Quality of Life for cancer patients. Like, if I find something that says drinking scotch is good for cancer patients, you can be sure I will let you know about it.)

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Right off the bat, one of the first things I see in the list of Follicular Lymphoma abstracts is a session called "Efficacy of Frontline Treatment Regimens in Follicular Lymphoma: A Network Meta-Analysis of Phase III Randomized Controlled Trials."

It's a big question for FL patients -- when it comes time for treatment, which is the best one? Or, for those of us who already had treatment, was the one I had the best choice, or should i have had another one?

Really, the questions comes down to, which treatment is the best one?

I'd like to tell you that this research answers that question, but it doesn't really, for a couple of reasons. I'll get to those soon.

The researchers noted that, in the last few years, there has been a lot of change in front-line treatment for Follicular Lymphoma -- the first treatment that patients receive after diagnosis. Since I have been diagnosed, we've seen approvals for Bendamustine, Obinutuzumab, and Lenalidomide.

Clinical trials involving these treatments have led to the approvals for these treatments, and have also prvided lots of data about their effectiveness. The researchers looked at the data from seven trials (FOLL05, StiL NHL1, BRIGHT, PRIMA, GALLIUM, StiL NHL7, and RELEVANCE) and then compared the results to one another.

The trials were all phase 3 (the largest numnber of patients involved), and were all randomized controlled trials. This is important -- a randomized controlled trial means that a group of patients is divided into two smaller groups, with one getting the standard treatment and the other getting the newer one that's being tested. It's the best kind of trial, since it lets researchers do a direct comparison between two treatments.

The measurement they used was Progression-Free Survival  -- how long it took before the patient's disease got bad enough to need a new treatment. Ideally, they's use Overall Survival, but with FL, there's usually not enough difference in OS to matter -- no matter which treatment, patients usually stay alive for about the same amount of time. But PFS can be very different.

First, they compared everything to B-R, Bendamustine plus Rituxan.

Here's what they found:

R-CHOP had a lower PFS.

These treatments had a similar PFS:
R-CHOP with Rituxan Maintenance,
Obinutuzumab + CHOP + Obinutuzumab Maintenance
R-Squared + Rituxan Maintenance

These treatments has a better PFS:
B-R with Rituxan Maintenance
B-Obinutuzumab with O Maintenance.


Then they did the comparison to R-CHOP with Rituxan Maintenance.

O-CHOP with O Maintenance, and R-Squared with Rituxan Maintence, had similar PFS.

B-R with R Maintenance and B-Obinutuzumab with O Maintenance had a better PFS.

Their conclusion is, basically, that some kind of maintenance is usually better than no maintenance -- if the measurement you are looking at is PFS, and only PFS.


So why doesn't this answer that important question, Which treatment is the best one?

Well, first of all, this data is limited to a particular set of recent trials. It's great information, but it also leaves out a bunch of older treatments (like straight Rituxan and Stem Cell Transplants, among others) and a bunch of newer ones (lots of inhibitors and CAR-T, among others). The choices here are great, but they're not the only choices.

Second, the research also looks at Progression Free Survival as its only way of measuring success. But it doesn't say anything about something like Quality of Life. A treatment could give you a PFS of 10 years, but have side effects (maybe nerve damage, for example) that make your everyday life less happy than it might have been with a treatment that gave you a PFS of 5 years, but with fewer long-term side effects.

So "best" isn't the same for everyone. It's important for us as patients to think of our own life goals. For some, the "best" treatment is the one that results in the longest time between treatments, no matter what. For others, "best" might mean frequent maintenance treatments, and the anxiety and inconvenience that might go with them, but an otherwise "normal" physical life (whatever that means).

To me, the lesson is the same it's been for 11+ years:

Stay educated and informed. Keep an open dialogue with your doctor. Know what matters to you. Advocate for yourself, and make sure that the treatment you get is the one that lets you live the life you want to live.

I'm looking forward to going through the ASCO abstracts some more. The conference starts on May. It's usually around that time that press releases start to come out, as people brag about their research results and measure the reaction that their presentations got. In the weeks that follow, experts will give commentary about which research they thought was most important.

We'll see if there's any Follicular Lymphoma news in all of that bragging.

Be a PEST

There has been a lot of Follicular Lymphoma research out there lately. The ASCO conference (American Society for Clinical Oncology) is coming up in a couple of weeks, and researchers are starting to give some previews of what they will be presenting. So my plan today was to get a head start on some of that and right about it today.

But this morning, I came across a really nice article called "I Am Not A Cancer Survivor, I Am A P.E.S.T.," written by Katherine O'Brien, a patient advocate for Metastatic Breast Cancer.

Metastatic Breast Cancer is a very specific type of breast cancer. I've heard a MBC patient say it is almost a completely different type. It's a stage IV cancer, and it is incurable. Patients who have it will need treatment for the rest of their lives.

Sound familiar?

I really connected with Katherine O'Brien's piece.

She's on her way to the ASCO conference (yes, I'm jealous), and she got her name badge in the mail. Because ASCO is such a huge conference, with lots of people there from the cancer world, name badges have ribbons on them to identify everyone's role. So when you meet someone, you'll see their name, but also something like "presenter," so you'll know this is someone who is presenting their research.

Katherine O'Brien's badge says "Patient Advocate" and "Survivor."

Again -- sound familiar?

She has no problem with the "Patient Advocate" ribbon. That's what she does -- help support other patients.

But the "Survivor" thing? She has some issues.

The term "Survivor" is a controversial one. Lots of cancer patients don't like it. I'm OK with it, personally. There are times when it seems like just making it through the day is something worth celebrating. To me, that's survival.

But I certainly understand that some patients don't like it.

For Katherine O'Brien, her dislike of it is tied to her having an incurable cancer. It's hard to think of yourself as a survivor when you know there is another treatment down the road. "Survivor" implies that it's all done with you. You made it through -- you survived.

I get it.

I usually refer to myself as a "Follicular Lymphoma Patient." I'm still seeing an oncologist 2 or 3 times a year. I know it's not over.

I like Katherine O'Brien's discussion of coming up with a name for herself. She settled on PEST -- Pragmatically Embracing Successive Treatments.

I like that it also embraces her role as a patient advocate. Sometimes we need to be pests -- it's the only way to help people -- to not stop.

Read the full article. It's worth it. Lots to think about.

The important thing, though, is that however you choose to think about yourself -- patient, survivor, PEST, or something else -- it's a term that lets you be who you are, and who you want to be, and encourages you to live your life in a way that makes you do the things you want to do.

Sunshine, Vitamin D, and Lymphoma

Interesting research from the journal PLOS One on Lymphoma and Vitamin D: Can spending time in the sun keep you from getting Non-Hodgkin's Lymphoma?

Please notice that I'm asking that as a question. I'm not entirely sure the answer is Yes (though that is what the researchers conclude).

The study is called "Vitamin D Status and Risk of Non-Hodgkin Lymphoma: An Updated Meta-Analysis."

As the title says, this study is a meta-analysis. That means the researchers didn't conduct a study on patients, the way many studies are done. Instead, they looked at a whole bunch of other studies that other people had done, and then came to a conclusion about what all of those studies might tell us.

That has some advantages (there's a lot of data from a lot of patients at different times), but also some disadvantages (different studies might have been conducted in different ways, using different methods, maybe with patients that are not very much alike, so they are hard to compare. As the researchers make clear, many of the patients in the studies they looked at were caucasian, and from North America).

I think that's important to be clear about before we get into this. They did NOT take two large groups of patients, make sure they were similar, and then compare them. They basically did a Google search of medical journal articles that mentioned vitamin D, sunshine, lymphoma, and related keywords, and then compared the results that they found.

(But, also,to be clear, that doesn't mean that kind of study doesn't have some value, either.)

The study looked at 30 other studies, involving over 56,000 NHL patients, looking at exposure to sunshine, Vitamin D intake through diet or supplements, and Vitamin D levels in the blood.

They found that people with high sun exposure had a smaller risk of developing NHL and various subtypes (including FL). Taking vitamin D supplements or getting it through food (which is pretty hard to do) didn't have any effects. Supplements are OK, but the body doesn't absorb the Vitamin D as easily as it does with the vitamin D that gets created by sun exposure.

I know this is a popular topic for a lot of you. There is some evidence that Vitamin D levels are important in preventing lymphoma, and for keeping it in check. It's not enough evidence to have oncologists say it's something we must all do (and this meta-analysis doesn't say that, either). So I don't recommend sunbathing as a lymphoma treatment.

But, in the interest of full disclosure, I will say that I do take Vitamin D every day. And since someone is going to ask, I'll tell you that I take 5000mg a day. My doctor recommended Vitamin D years ago, and I used to take 1000mg in the summer (when I got more sun exposure) and 2000 in the winter (when I got less). Two years ago, my levels were low, so she recommended I go up to 3000 year-round. I went with 5000 because it was easier to take one pill that three 1000mg pills.

I live in the northern United States where the sun isn't as strong as other parts of the world. I am fair-skinned, and I don't spend a lot of time in direct sunlight, because I don't need to add skin cancer to my list of health issues.

So, to be clear: I don't think my Vitamin D levels have anything to do with my status as a Follicular Lymphoma patient. In other words, I don't think taking Vitamin D is the reason I haven't needed treatment for 9 years. I take it because I've read enough about the health benefits -- many of them, that don't include cancer -- and my doctor recommended it. It's an easy, and (for me) inexpensive thing to do, and that makes it worth the chance that it will help me.

As with everything, it's good to do some research, and then talk to your doctor about what you've found out. I'm not a doctor, so my experience should not be taken as medical advice.

It's also good to remember that there are no shortcuts to curing or controlling cancer, and a 25 cent pill or a day at the beach probably won't do that job.

But Fake Dr. Bob is happy to give you this prescription: on a sunny day, put on some sunscreen and a hat and sunglasses and spend a little time outside. Go for a walk. Weed your garden. Pick some fruit. Feel the warmth on your face. Remember and enjoy little things that make you appreciate being alive, even if it's just for a few minutes.

Mental Health Awareness Month

May is Mental Health Awareness Month.

I have said for a long time that Follicular Lymphoma is as much an emotional disease as it is a physical one. For many of us, we watch and wait before receiving treatment, sometimes for months or even years. For those months and years, we're not dealing with any physical symptoms.

But we have plenty of emotional symptoms -- fear, anxiety, worry, sadness. That's all part of our mental health. We shouldn't ignore that any more than we ignore our physical health. There's no sense in being physically "healthy" if we are mentally and emotionally "unhealthy."

I don't mean to suggest that people who don't watch and wait do not have emotional and mental needs, too. Quite the opposite.

This past week, I saw an interview with Alex Trebek, the host of the TV game show Jeopardy!. Trebek was diagnosed with stage 4 pancreatic cancer a few months ago, and is in treatment now. He says he goes through "surges of deep sadness" as he deals with his diagnosis and treatment.

His advice? "Trebek, 78, encouraged others undergoing chemotherapy to be open about moments of depression, even if they are unable to express the reasons behind the bouts of sadness."

Think about that for a second. People going through chemotherapy, and they can't explain why they are sad?

It seems pretty obvious why they'd be sad -- they're going through chemotherapy.

And yet, sometimes it's hard to put into words.

So this is your annual reminder to "be open," to talk to someone if you're feeling sad, or angry, or overwhelmed. Maybe it's because you're a cancer patient, or love someone who is. Maybe it's something else.

But there's no point in suffering in silence.

Maybe just talking about it to a friend or a loved one is enough to feel better.

Maybe just talking doesn't help, and you need someone more experienced, a professional, to help you through it. That's OK, too. Take the step.

But whatever you do, don't be afraid to take care of your emotional and mental health. It's just as important as your physical health.

I wish you all good health -- physical, emotional, and mental -- and the strength to take care of yourselves in any way you need to.

Polatuzumab for Follicular Lymphoma

A recent article in The Lancet Haematology reported the results of a phase 2 clinical trial for two Antibody–drug conjugates (or ADC).

An Antibody-drug conjugate is kind of a step up from monoclonal antibodies like Rituxan, because it uses what's great about a monoclonal antobody (it can seek out a protein on a cancer cell), but also adds something to the party. The "conjugate" is an add-on, in this case, a treatment that can mess with the cancer cell. So the antibody part of the conjugate finds the cancer cell, and then the targeted treatment part of the conjugate gets into the cell and does some work to kill the cell.

ADCs are a great idea, but also complicated. They have three parts that all need to work well: the antobody that targets the cell, the treatment that kills the cell, but also the link that holds them together. But if it does all work well, then ideally you have a very targeted treatment -- unilke traditional chemo, the treatment is delivered right to the cancer cell, rather than getting to lots of healthy cells as well.

The article is called "Polatuzumab Vedotin or Pinatuzumab Vedotin Plus Rituximab in Patients with Relapsed or Refractory Non-Hodgkin Lymphoma: Final Results from a Phase 2 Randomised Study (ROMULUS)."

In the study, researchers compared two ADCs plus Rituxan, with half of the patients getting the ADC called Polatuzuman Vedotin and the other half Pinatuzumab Vedotin. To make it easier, the authors very kindly call them R-Pola and R-Pina. Some patients in the study had Follicualr Lymphoma, and some had Diffuse Large B Cell Lymphoma, FL's more aggressive cousin. All of the patients were Relapsed or Refractory -- their last treatment had stopped working.

R--Pola worked better than R-Pina.

42 patients with DLBCL received R-Pina, with 60% achieving a response, with 26% a Complete Response. 39 had R-Pola, with 54% getting a response (26% a CR).
For the Follicular Lymphoma group, 62% had a response to R-Pina (5% a CR). For R-Pola, 70% had a response, with 45% getting a CR.

Side effects were common for all groups, with 62% of the FL group getting fairly serious side effects from R-Pina, 50% for R-Pola. Side effects included infections, nerve issues, and blood cell problems.

In the end, the researchers are recommending further research on R-Pola, but not R-Pina. The responses lasted longer for R-Pola, and the seriousness of side effects seemed to outweigh the benefits for R-Pina.

So we can probably expect to see more from Polatuzumab Vedotin. The antibody part of ADC works by targeting CD79b, a protein that is found on B-cell lymphocytes. (Rituxan targets CD22, in case you wated a comparison). The anti-cancer part of the ADC is called Monomethyl auristatin E, or MMAE. It's an antimitotic, which means it stops mitosis, the process that cells use to divide and create more cells. So it keeps the cancer cell from growing into more cancer cells.

 Polatuzumab Vedotin was given Priority Review designation a couple of months ago when used in combination with Bendamustine and Rituxan for Relapsed or Refractory DLBCL. It's in a bunch of other clinical trails, in various combinations, against a few different types of blood cancers. We'll be hearing more about it soon, I'm sure.

Definitely one to keep an eye on.