ASCO: Too Many Inhibitors?

There are still a few things to talk about from the ASCO conference, but I saw an article this morning that I found really interesting. It basically says something that I have been wondering about for a couple of years -- are there too many inhibitors out there? Do we really need any more?

The article is called "Post-ASCO News Alert: Mei Pharma’s Phase II zandelisib in r/r follicular lymphoma draws expert pause on clinical value; side-effect edge doubtful," and it was posted today in Clinical Trial Arena. It isn't really reporting on research so much as questioning why the research is happening.

The article features some lymphoma experts discussing the results of clinical trials for Zandelisib. There were three presentations at ASCO this year that discussed results of Zandelisib. The results were good. But the question is, according to the article, are the better -- more effective or safer than the four other PI3K inhibitors that have already been approved for use on Relapsed or Refractory Follicular Lymphoma. Those are Idelalisib, approved by the FDA in 2014, Copanlisib in 2017, Duvelisib in 2018, and Umbralisib in February 2021.

The reason that four of the same kind of treatment have already been approved is because they are all slightly different. While they all inhibit the same process that is necessary for a cancer cell to survive, there are actually a few different variations of that process, because there are a few different variations of one of the proteins involved. They are the same in many ways, but different in some ways, too. 

So far, from what I can tell, the differences don't seem to make all that much of a difference. In other words, there isn't one inhibitor that whose difference makes it stand out all that much from the others. I'm sure the makers of the different inhibitors would disagree, but I don't see any consensus on one being "the best."

And that's the issue with Zandelisib. Is there enough evidence from trials to show that it will be more effective, or safer, than the other options already available? Those experts in the article don't seem to think so.

It's a tough situation for a pharma company, I'm sure. If they've already spent millions developing a treatment, they'll probably want to see it approved so they can make some sales and make back some of that money. Or maybe they think their treatment can help some people that otherwise wouldn't be helped. (If you're cynical, you might not believe that last one, but the people I have met who work for pharma companies do seem genuinely interested in helping others.)

The problem, though, with having so many treatments that do the same thing, without being hugely different from one another, is that it creates confusion for patients, who have too many choices (and maybe for some doctors, too). Worse, in my opinion, is that all of the money that went into developing a treatment that duplicates other treatments could have gone to developing some new approach.

But that's hard to know from the start. I've been a grant reader for cancer research (more on that soon!), and seeing a scientist describe early research is exciting. There's lots of hope and promise that this research project might be The One. And maybe it isn't until much later in the process when it becomes clear that The One is really just Another One. Still helpful to some people. Just not what everyone was hoping for. 

So I found the article interesting at first because it expressed my frustration -- there seems to be a lot of duplication in cancer treatment. Lots of inhibitors, lots of Rituxan biosimilars, etc. But then, as I thought more about it, it reminded me of how difficult it must be to try to create a new treatment, especially when you know that a bunch of other people are working on a similar project, and might do it faster than you. But it also makes me appreciate that we do have choices, and in the end, that's a good thing.

Looking at all of the presentations at ASCO on Follicular Lymphoma, it's still exciting to think that one of them might be The One some day. Here's hoping that some new treatment still in development gets to patients soon, and dies the job better and safer (and maybe longer) than everyone else.

ASCO: Copanlisib and Rituxan

There was a lot of CAR-T news coming out of ASCO -- much more than I have shared. And most of what I have shared is related to CAR-T in some way.

But one of the other big trends that I saw had to do with inhibitors -- treatments that inhibit cancer cells from growing and staying alive. For any cell to stay alive, there is a long path of reactions that need to take place -- genes telling enzymes and proteins to tell other enzymes and proteins to do certain tings, or stop doing certain things. Cancer happens when some part of that path goes wrong, and things that were supposed to stop don't stop, or things that were supposed to happen don't happen. Inhibitors are designed to stop something form happening, so the pathway gets blocked, and the cancer cell dies.

There are four inhibitors approved for use with Follicualr Lymphoma: Umbralisib (approved earlier this year), Idelalisib, Duvalisib, and Copanlisib (which I wrote about January). All are PI3K inhibitors (meaning they try to stop the same path, though by targeting slightly different things in that path), and all have been approved for different FL populations. 

A lot of the research on PI3K inhibitors has looked at their usefulness as part of combination therapies -- mixing the inhibitor with something else. Combinations of all kinds are important treatment options for FL, and they recognize how complex a disease it is -- cancer cells are tricky, and probably need more than one to get at them in order to be successful. Combinations are often more effective than the individual parts.

The problem, of course, is safety. Two different treatments might get at cancer cells in different ways (making them potentially twice as effective), but they also each come with their own side effects (making them potentially twice as dangerous). Like any treatment, the PI3K inhibitor combinations have to show that their improved effectiveness is balanced by their safety.

The ASCO presentation called "Copanlisib + rituximab versus rituximab + placebo in patients with relapsed follicular (FL) or marginal zone lymphoma (MZL): Subset analysis from the phase III CHRONOS-3 trial" seems to show just that. 

The presentation reports on results from a phase 3 clinical trial called CHRONOS-3 that looks at Copanlisib and Rituxan by comparing them to Rituxan and a placebo (in other words, comparing them to just Rituxan on its own). 

The title calls this a "subset analysis." That means the research are reporting on a smaller group within the larger group of patients who are in the trial. In this case, the smaller group includes patients with indolent NHL, including Follicular Lymphoma patients, as well as Marginal Zone Lymphoma patients. (In case you're curious, the others not included in this presentation were patients with small lymphocytic lymphoma and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia.)

The effectiveness was very good.  The Overall Response Rate for the C + R group was 82.4% (including a 37.6% Complete Response), and for the Rituxan group it was 50.8% (with an 18.3% CR). The median Progression Free Survival was 22.2 months for C + R and 15.4 months for R.

More importantly, safety was also good, though (maybe not suprisingly) the C + R group had more side effects, with the most common grade 3 or worse (that is, serious) being hyperglycemia (56.4%), hypertension (39.7%), and diarrhea (4.9%). The C + R group had more serious side effects (47.2%) than the R group (18.5%). And 2% of C + R patients had a grade 5 side effects (the most serious) versus 0.7% in the R group.

Given the way things are described in this presentation, it seems like the Copanlisib + Rituxan combination is probably going to be marketed as a treatment for patients who have already tried at least a couple of other more aggressive treatments, especially those who might not physically be able to handle something more aggressive and harder on the body. The makers of Copanlisib filed for FDA approval for relapsed indolent NHL (including FL), so if it is approved, it would cover a wider range than the one I mention. But that seems to be what it's being aimed at. (They are also seeking approval from the European Medicines Agency, but only for Marginal Zone Lymphoma, not FL -- not sure why.)

As I said, this was one of many presentations on inhibitors. I'm sure we'll see more approval applications for them in the months and years to come.

ASCO: CRSPR and T-cells

As I said before, ASCO is fascinating to me because it doesn't just tell us where we've been (by looking back at how successful treatments have been over the past few years). But it's also fascinating because it gives us a glimpse of the future.

I've been looking at phase 1 clinical trials in the ASCO abstracts. As you may know, before a treatment can be approved, it goes through three different stages of clinical trials, each involving more patients. It can (and usually does) take years for a treatment to be studied enough to know that it is effective and safe. 

Phase 1 typically involve a small number of patients, and focus on safety and "dose escalation" -- figuring out how much of a treatment to give to patients to that it is safe while being as effective as possible. Too much of something might kill more cancer cells, but also create more side effects that harm the patient so much that the effectiveness isn't worth it.

One of the interesting phase 1 studies I looked at was described in a presentation called "A phase 1 dose escalation and cohort expansion study of the safety and efficacy of allogeneic CRISPR-Cas9–engineered T cells (CTX110) in patients (Pts) with relapsed or refractory (R/R) B-cell malignancies (CARBON)."

This one is so new that it doesn't even have results yet. The presentation is a description of what they plan to do in the phase 1 study called CARBON.

The study will involve mostly Diffuse Large B Cell Lymphoma patients, but will also include Follicular Lymphoma Grade 3b patients, since FL 3b is often considered almost a separate, aggressive lymphoma, different enough from indolent FL that they're not even the same disease anymore.

What made me so interested in this presentation was its use of CRSPR technology. That's a pretty new technology, and worth some explaining. It's controversial in many ways, but exciting in many ways, too.

The idea for the study comes from what the researchers see as one of the weaknesses of CAR-T -- its use of autologous T cells (that is, taking T cells from the patient and changing them before putting them back). The problems include cost (it takes a lot of work to change the T cells), time (it can take a couple of weeks to take out the cells, change them, grow them into large enough numbers to be effective, and then put them back in the patient), and T cell failure (they don't do what they were supposed to, which is find and kill the cancer cells).

Another possible option would be allogeneic CAR-T treatment. Instead of taking cells from the patient, the cells are taken from someone else. They can be grown into huge numbers and kept available for use by any patient. So instead of waiting two weeks, the treatment could start almost immediately. And since they don't need to be specially made for each patient, they can be made more inexpensively. 

The problem with using someone else's cells is that our bodies don't like to have stuff in them that doesn't belong there. This is what happens with Stem Cell or Bone Marrow Transplants. An autologous transplant involves removing a patient's stem cells, wiping out the immune system with aggressive chemo, and then putting the stem cells back in so they can grow quickly into immune cells and protect the patient. Auto SCT is usually safe but not always as effective as allogeneic SCT, which involves someone else's stem cells (often a relative). But the patient's body might reject the stem cells, since they see them as not belonging, the same way they'd see a bacteria or virus. It can be dangerous.

So if using another person's T cells for CAR-T has some advantages, how do you get past the potential problems?

CRSPR technology might help.

CRSPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. Basically, CRSPR involves finding a segment of DNA in a cell, and then "editing" it by removing that segment and replacing it with another one. 

Think of it this way. There's a small segment of DNA that controls the color of our eyes. Suppose we wanted our baby to have beautiful blue eyes, a tribute to Frank Sinatra. In theory, CRSPR technology could be used to find and remove that segment of DNA, and replace it so the baby had blue eyes. 

That's the very controversial part of CRSPR technology, and there are huge ethical issues surrounding it. Used improperly, it could mean that some people are able to create people that are "perfect." That's not good. Lots and lots of problems there.

But not all uses of CRSPR are so potentially sinister. And that includes the one described here.

For the CARBON trial, researchers are working with previous studies to show that certain segments of DNA can cause problems with allogeneic transplants. By using CRSPR technology, they hope to change T cells by cutting out those problematic parts of the DNA and replacing them with DNA sequences that won't cause those problems. There won't be any use of CRSPR to change the patient receiving the cells. 

The trial will involve patients with aggressive lymphomas, including FL 3b. They will be screened, then given a chemo regiment to wipe out most of the cancer cells, and then given CRSPR-manipulated T cells to wipe out the rest of them. And since T cells stay in the body and multiply when needed, if the cancer cells come back, the T cells will be there to go after them again. Patients will be followed for 5 years to see how well the treatment continues to work.

Will it work? I'm not sure. It will be interesting to see if there are positive results in the years to come. The researchers are continuing to recruit patients.

But the bigger lesson here, I think, is that CRSPR technology is going to become a big part of cancer research in the years to come. You might remember that last last fall and winter, I was a patient representative for a couple of programs that gave money to cancer researchers for their projects. There were several projects involving CRSPR technology in those programs (not necessarily for FL). We might not see results immediately, and they might not be for Follicular Lymphoma, but I think it's going to change things for a lot of cancer patients in the future.

ASCO: More CAR-T Results

As you know, because you pay attention to such things, CAR-T is a big deal in the world of lymphoma. I would say the big CAR-T news from ASCO for Follicular Lymphoma patients was the presentation on Kymriah (also known as tisagenlecleucel, or Tis-cel) and Relapsed/Refractory FL. We've known that CAR-T is effective for many FL patients. This research, from the phase 2 Elara Trial, also showed that it was much safer than Yescarta, the CAR-T treatment that has already been approved by the FDA for R/R FL. While 8% of Yescarta patients in the ZUMA-5 trial showed serious Cytokine Release Syndrome symptoms, none of the Elara patients did. That's major.

Still, the updated Yescarta (also known as Axi-cel) results at ASCO were also very good. They were reported in the presentation called "Interim analysis of ZUMA-5: A phase II study of axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory indolent non-Hodgkin lymphoma (R/R iNHL)." The trial included mostly FL patients, but also some with MZL, another indolent lymphoma.

Like Elana, the ZUMA-5 trial is a phase 2 trial. While Tis-cel had a better safety profile, Axi-cel did better with effectiveness -- 95% Overall Response Rate for FL patients (compared to 86% for Tis-cel), and 81% Complete Response for FL (compared to 66% for Axi-cel). 

After a median follow-up of 15 months, about 68% of the Axi-cel patients were still enjoying their Response. About 80% of those with a Complete Response were still responding.

I haven't seen a direct comparison of the two CAR-T types for R/R Follicular Lymphoma patients yet, but I'm guessing that one is coming soon. The question is inevitable -- which one is better?

I'm looking forward to an actual oncologist giving an opinion on this, but here's my guess on what that will be -- if you have talked to your doctor about treatment options, and you have the opportunity to get CAR-T, and only one is available to you, go with the one that is available. It will kind of be like a Covid vaccine -- both CAR-T types are effective and safe, one maybe a little more effective than the other, and one a little safer than the other. But both still good.

That's my guess, anyway.

CAR-T is still a while from being the only choice for FL. There's the issue of cost, which is significant. It's not 100% effective on every patient (though that number seems to be getting better all of the time). And it's potentially hard on the body, so it's possible that patients with other health issues might not be the best candidates for CAR-T.

But it's being studied a lot, and experts are very excited about the results of those studies. I really do think it's going to be a part of many of our futures, in some form.

My Apologies

I started to write this as a comment, in response to a comment by Paul on my first ASCO post. But as I write it, I'm thinking I should probably put it here where it's easier to see.

Let's start with Paul's comment:

My Doctor over at the City of Hope near Arcadia, CA was saying CAR-T was a possible cure to follicular lymphoma should mine relapsed and highly encouraged me to go that route. Told him I do not want to be the experiment. In your last blog, you stated a 95% chance of FL returning. I was disheartened yesterday seeing this. Was hoping for better odds. I do hope that CAR-T ends up being a cure for FL at some point. I am encouraged that an oncologist says 20 years or more a person can live with FL. I'm still trying to see how. If first line on average last about 3-3.5 years, and 2nd lines and beyond usually are less effective, a person can be doused with so much toxicity not sure how they make it that long. Thank you for all the great information you provide.

Paul B. 

And now my response, because there are a things to reply to here.

Hi Paul.
First off, I should apologize to everyone. I didn't do a great job with that post. If you read Rodrigo's comment, you saw that I might have messed up the numbers (though I still think I read them correctly and they were revised before I published the post). And here, with the "95% return" comment -- I could have stated that better. Not a great post. Just too much of a rush job. Life has been getting in the way lately.

So let me refine what I said, and maybe add a little more detail.

I'll blame the abstract a little bit for this, because it's not very clear, though I'll blame myself most for not pointing out that it was unclear. The abstract says " We selected pts aged ≥18 years, with an initial FL diagnosis (ICD-9-CM: 202.0x; ICD-10-CM: C82.0x) between January 2011 and July 2020, who had received ≥1 line of therapy (LOT) for FL (follow-up ended September 2020)." Later on, it says "Most pts received up to 2 LOTs (n=2258 [94.8%])." (My emphasis, not the researchers'.)

That's two times saying the same thing, but in two different ways:

 Patients had greater than or equal to 1 line of therapy = Most patients received up to 2 lines of therapy  = most patients had either one or two rounds of treatment. 

As I read that, I took it to mean most patients had two lines of therapy. I'm less confident that the statistics say that, though I'm still not sure exactly how many patients had just one line of therapy. 

More importantly, to respond to Paul's concern, I think the sample of patients studied is skewed toward those who were diagnosed closer to 2010. That's important for a couple of reasons.

First, I think this is skewed because of the treatments being discussed. The most popular are fairly old school treatments: Benda, CHOP, Rituxan. There isn't much Obinutuzumab, and R-squared and CAR-T aren't even mentioned. Now, it's a necessary thing -- to collect as much data as possible, researchers have to go back a few years. But doing so gives equal weight to patients, treatments, and practices that are 10 years old. That matters -- the FDA has approved 14 treatments for FL since 2010. Each year of this study means looking at patients who had fewer treatment optionss available, and most treatments show some increase in effectiveness over what has already been available (others show better safety, or are completely new types of treatment).

So a retrospective study like this is going to have some limitations built in. As much as it claims to show "where we are" (and I used that language myself), it's more like "where we've been" -- not what's happening right now, but what happened 10 years ago, 9 years ago, 8 years ago, etc. That's not the same thing.

There are still plenty of patients getting B-R and R-CHOP, but more and more are getting CAR-T, Rituxan biosimilars, Obinutuzumab, and R-squared. I say that based on my sense of what's happening in online discussion groups, where patients describe their treatments. Ideally I'd have numbers from 2020 that showed all of that. I don't have them, and I don't think they're available yet.

But here's the point: treatments are getting better. More effective and safer. More Effective means more time between treatments, and possibly enough time that there is a cure, or an "effective cure" (a patient dies with the disease at same age as the general population's median life expectancy. And Safer means the toxicity from newer treatments is less than with something like traditional chemotherapy. 

The problem is, we can't really know how much more effective and how much more safe until its measured over time, say 10 years. And by that point, the data is in some ways outdated. 

As Dr. C, the lymphoma specialist that I saw many years ago, warned me back then: Anything you see online is already out of date. 

And one quick aside -- CAR-T might very well cure some people. That's another thing we'll need time to know for sure.

So, to sum all of this up: Paul, I absolutely understand your worries, and I'm sorry that the things I wrote contributed to them. That's never my goal. I like to think I'm am hopeful but realistic,but most of all accurate, and I've thrown away of dozens of posts that I started by never finished because I wasn't completely sure about what I was saying. I should have taken the time to be as clear and accurate as I can be. I owe you all that much.

At the same time, I do still think there's plenty to be hopeful about. The abstract shows Time to Next Treatment for first line treatments is a median of 79.4 months -- about 6.5 years. For 2nd and later lines, it's about 3 years. (That's much higher than the 3.5 years you're giving the first line treatment, Paul.)

And remember, that's the median, which means half will be lower than that, but half will be higher. I'll give myself as an examle of the "half will be higher" -- 11+ years from Rituxan. Plenty of others have gotten that and more from B-R, R-CHOP, and a whole lot of other treatments. 

And then there's median Overall Survival, which hasn't even been reached yet for this study. 

I don't know if all of this makes anyone feel better, but it makes me feel better to remind myself of these things, and to make sure I'm being clear. 

I'll have more from ASCO soon. Take care, everyone.

ASCO: CAR-T and R/R Follicular Lymphoma

I'm still working my way through the ASCO materials. I didn't get to see as many of the sessions live as I would have liked. (I had a visit from a vaccinated relative whom I hadn't seen in a while. That was worth the trade-off. I miss people.)

As I said before, I'm still not sure there was anything from ASCO that was a kind of game-changer for Follicular Lymphoma. But there were some definite trends, and one of those was the attention being paid to CAR-T for Follicular Lymphoma. In fact, there were 32 different sessions devoted to CAR-T and FL. Some of them looked at CAR-T types that have already been used on FL, and some were on new types of CAR-T.

(It's probably worth reminding you that CAR-T isn't one specific treatment, the way Rituxan is one specific treatment. Instead, it's a larger category of treatments, like chemotherapy or immunotherapy with several different specific types of CAR-T available. They all work the same basic way, but with some important differences that make each one special.)

If there was one session about CAR-T and FL that got people buzzing the most, it was probably "Efficacy and safety of tisagenlecleucel (Tisa-cel) in adult patients (Pts) with relapsed/refractory follicular lymphoma (r/r FL): Primary analysis of the phase 2 Elara trial."

So far, there have been two main CAR-T treatments that have been approved for Follicular Lymphoma. Both were approved for aggressive FL types, especially transformed FL. And both have been in trials to test how effective and safe they might be for other types of FL, like indolent refractory/relapsed FL (slow-growing, but stopped responding to treatment), or as front-line treatment (the very first treatment for a patient). 

One of the two, Yescarta, was approved in the U.S. a few months ago for use on R/R Follicular Lymphoma. The approval was based on the ZUMA-5 trial, and showed an Overall Response Rate of 91%. Very good stuff.

The paper linked above described results for a study of the other CAR-T that has been approved for some FL patients (those with aggressive FL) -- Kymriah (also known as tisagenlecleucel, or Tis-cel). Kymriah was the first CAR-T approved for anything in the U.S. (in 2017), beating out Yescarta. But Yescarta beat Kymriah is getting approved for R/R FL. A nice rivalry going there, if it means better treatment for all of us.     

In the phase 2 Elara trial, described at ASCO, Kymriah was administered to 98 FL patients. The patients had received between 2 and 13 treatments, and 60% had progressed within 2 years of receiving immunochemotherapy. In the end, 94 patients were able to be evaluated, and there was an 86% Overall Response (with a 66% Complete Response). That's slightly lower than Yescarta, but still an excellent rate.

But here's where things take a turn in Kymriah's favor -- safety. 65% of patients experience serious side effects, generally nerve-related and blood-count-related (as is typical in blood cancer treatments). But while 49% had some kind of Cytokine Release Syndrome, none had a serious CRS reaction.

Let's look at that again. Cytokine Release Syndrome (or a Cytokine Storm) has been the major problem with CAR-T. Essentially, when the immune system is being overloaded, the way it does with CAR-T, when T cells flood the body, an inflammatory response begins. The body releases cytokines, which signal other immune cells to be released, and the result is a very large immune system reaction which can lead to organ failure. Early CAR-T trials resulted in a few deaths from CRS, though researchers learned to recognize it quickly and deal with it before it became too serious.

About 8% of FL patients in the ZUMA-5 trial for Yescarta had serious CRS. But in the Kymriah trial described at ASCO, no patients had serious CRS reactions. That's a pretty major difference between the two.

The question is, will that carry over into a larger group? Fewer than 100 patients were in the trial -- normal for a phase 2 trial. But not a huge number. Word is that the maker of Kymriah will ask for FDA approval for R/R Follicular Lymphoma based on these numbers, and my guess is that the approval will come quickly. But I'd be very interested in a follow-up (maybe at ASH in December, or ASCO next year?), to see if it really is as safe as this trial suggests. Even if those numbers go up to the 8% that Yescarta has, it will still be pretty great. But if there has been some tweak in the last 4 years that has made it even safer, that would be pretty amazing.

I'm going to look through some of the other CAR-T abstracts from ASCO for more good stuff. CAR-T is going to be with us for good. It will be interesting to see if new versions are more effective/safer than the older ones, can be made more inexpensively, or have some other features that will make CAR-T the standard treatment for all of us, no matter where we are in our treatment time line.

ASCO: Real World Treatment Patterns for Follicular Lymphoma

The ASCO conference starts in a few days, and I'm lucky enough to be able to attend (online), but I've been making my way through the abstracts so I can figure out which sessions will be worth attending.

But I did find one that I can write about without attending the actual session live. And I think it's a good one to begin with. ASCO presentations tell us a lot about our possible future; this one looks at where we are right now.

It's called "Real-world treatment patterns and outcomes in patients with follicular lymphoma in the United States."

The reason I find this so interesting is because it looks at our immediate past -- how Follicular Lymphoma patients have actually been treated over the last 10 years or so. We've seen so many exciting treatments go through clinical trials -- how many of them actually end up in patients' bodies?

The study looked at electronic records for patients from 280 cancer centers in the United States who received treatment between January 2011 and July 2020. The researchers looked at the records of 2383 patients (they didn't count patients with grade 3b and a few other special situations), and measured a whole bunch of things about treatment type and the success of the treatment. And this is important: they didn't count patients who didn't receive any treatment yet, so it doesn't measure active watch-and-waiters.

In that group (and it's a pretty large group), the median age at diagnosis was 66 years old -- very much in line with what we've always known about FL. (I was diagnosed at 40, making me an outlier.) 77.5% of the group had low-grade FL, meaning grade 1 or 2. Again, not a surprise, in my experience. And 75% had advanced stage FL (stage 3 or 4, again not a surprise). 

About 95% of patients in the study had received 2 or more treatments. I think that's important to note. I was told from the start that FL was something that would likely come back at some point (and I'm still assuming it will for me, even though it's been 11 years since I needed treatment). I hope that brings a little comfort to people who relapse -- 95% of the time, it's going to happen. It's probably good to be prepared for it, emotionally, and in terms of a treatment plan. 

As for which treatment were most common, these are the percentage of patients who received these treatments at some point, whether as first, second, or later treatments:

Rituxan + Bendamustine: 52.7%

Rituxan only: 34.1%

R-CHOP: 20.3%

R-CVP: 7.2%

Obinutuzumab + Bendmustine: 3.2%. 

Once again, none of this is surprising to me, given that the study started looking at patients from 2011. Obinutuzumab really started picking up as a Rituxan alternative in the last couple of years, for example, and Rituxan has been around so long (since 1997) that most doctors are probably just in the habit of using it, so they will continue to do so.

 In fact, that attitude probably explains a lot of treatment decisions.

 As for patients who receive a 3rd treatment, it is more common for newer treatments to be used at that point:

R-Squared (or Obinutuzumab + Lenalidomide): 2.3% overall and 19.2% of 3rd line treatments

Inhibitors of all kinds: 1.6% overall, 21.6% of third-line treatments.

Again, to me, this is not surprising. I do like to look at videos and articles from oncologists who talk about how they typically treat FL patients (like this one from a couple of weeks ago), and that pattern holds -- for a fairly aggressive FL, try R-B first, reserving R-CHOP for possible transformation. Then maybe try a different imunochemo, and then try one of the new non-chemo alternatives like those above.

So, as I said, I think this is interesting because it tells us where we are right now -- what kinds of patterns there are in the way FL patients are treated. A lot of that is influenced by things like NCCN guidelines, which make recommendations for treatment patterns. In my experience (having had 5 oncologists myself, and talking to many of you), it seems like a generalist oncologist is likely to follow NCCN guidelines pretty closely, while a lymphoma specialist seems more likely to try something a little different, and maybe recommend a clinical trial. That's not true of every oncologist, but it does seem to be a pattern. My guess is that the same holds true in other countries -- a national health service will recommend a certain pattern of treatments.

 I think if it's possible, it's worth getting a second opinion from a specialist after an oncologist has made a treatment recommendation. It seems to me that there are still some treatments out there (like RadioImmunoTherapy) that don't get much use, but which could be very effective for some patients. A specialist is likely to know if you are one of those patients.

It's also important to remember that is is a retrospective study -- literally a "looking backwards" study that covers almost 10 years. Newer treatments like inhibitors, R-Squared, and CAR-T (which isn't even mentioned) are all very new, and might very well become more popular in the next few years.

So here are the lessons (from me, a non-doctor who reads a lot about cancer):

Get second opinions when you can, from lymphoma specialists. They will know what is available and who it might be best for.

Participate in clinical trials when you can. New treatments and treatment combinations won't get used unless there is data to show how effective they are, and data will only come from clinical trials. If you have the option, give it serious consideration.

Finally, stay informed. The whole idea behind this blog is that it's important to stay informed -- that's why I write, to keep myself informed. I'm not a doctor, and you shouldn't take anything I say as medical advice. What I do hope is that you'll know enough to be able to have a good conversation with your doctor. You'll be able to ask the right questions. You'll be able to say, "I understand why you are recommending that, but what about this instead?" 

So that's where we are right now. I'm looking forward to more ASCO, so I can learn about where we might be going from here.