Idelalisib Under Review

News out of Europe today:

The European Medicines Agency (or EMA, which is sort of like the FDA in the United States) announced that they were going to review Idelalisib, base on some problems from a couple of trials. One of the trials involves Follicualr Lymphoma.

Before we get to the reason, let's make sure this is clear: The EMA says that anyone who has been taking Idelalisib without any problems should continue to take it if it's working. There are many, many people who are in that situation -- Idelalisib has been great for them, and they have had no unexpected side effects.

However, in three trials in Europe, patients with CLL and with indolent NHL (including Follicular Lymphoma) have been having problems with infections. Unfortunately, some of the "increased rate of serious adverse events" have included patient deaths. The maker of Idelalisib has halted the trials, though they point out that the trials are not using Idelalisib in the same way that they have already received approval for them (the trials are looking at combinations for CLL, and the FL trial involves disease conditions that are different from those that the patients had when it was approved for them).

The FDA has not taken similar steps. According to one article, "The US Food and Drug Administration (FDA) spokeswomen Angela Stark: 'FDA is also looking into this serious matter in relation to the deaths of the patients during the clinical studies.' She added: 'The safety of patients is a top priority and the FDA will communicate new safety-related information on Zydelig as it becomes available'."

Some important things to consider:

First, Idelalisib has been working very well for a lot of people. This does not mean the end of Idelalisib. That arrow stays in the quiver.

Second, I read about a dozen articles that discussed this situation, and they were pretty much all from a business perspective -- sites for people who are interested in investing in the company that makes Idelalisib. And they all say the same thing. I haven't seen (yet) anything from a medical or oncology site that gives any kind of analysis. I hesitated to even write about this just yet, but I saw more and more articles about it, and I figured I should look into it. I'm still looking.

The kind of language the articles use is interesting -- they say the trials involved Idelalisib being used in ways "that were not approved," almost liken they had uncovered a scandal. Of course they weren't approved -- that's the whole point of a trial.

So my take on it, for what it's worth, is that this situation bears watching. I don't think Idelalisib gets pulled any time soon. It will mean watching patients more closely to make sure they aren't more prone to infections than suspected (and I'm guessing the increased infections are coming from Idelalisib doing its job of destroying infection-fighting white blood cells to begin with).

No reason to give up hope just yet.

But there's no reason to think any treatment is a miracle that won't come with some challenges either.

Idelalisib / CAL-101 / GS-1101 News

Big news yesterday from Gilead, the maker of Idelalisib (also known as CAL-101 and GS-1101). It's not related to Idelalisib as a treatment for Follicular Lymphoma, but I think it's exciting and significant anyway.

Gilead announced that their phase 3 trial for Idelalisib in Chronic Lymphocytic Leukemia (CLL) patients will be stopped because it's going so well.

CLL is similar in some ways to Follicular Lymphoma, on that it affects B cells, and is generally slow-growing (in fact, while CLL is considered a leukemia, SLL, which is essentially the same disease but shows up differently, is considered an indolent lymphoma. To-may-toe, to-mah-toe.

As for the study, it focused on patients who had previously been treated, but were not good candidates for chemotherapy. Idelalisib, with fewer side effects, can be handled better than traditional chemo.

In the study, half of the patients received Idelalisib, and the other half received Rituxan. The preliminary results were so good, in terms of progression-free survival and safety, that Gilead was advised to stop the study. The advice came from an independent organization, not the FDA. The next step is for Gilead to negotiate with the FDA to see if they can get approval for Idelalisib. Maybe that will happen; maybe the FDA will ask that the study be continued.(I don't know if Gilead is considering that possibility, though they are continuing to treat the patients who are receiving Idelalisib).

From what I know of the FDA process (and I'm no expert), it seems like a slightly risky maneuver. There's no guarantee that they get early FDA approval. on the other hand, it seems like they could get conditional approval, and be asked to continue the study -- not so bad, either. They have a couple of things on their side: an independent agency making the recommendation, and the fact that there really isn't anything else out there for CLL patients who can't do traditional chemo. 

So why am I so excited about this, given that it isn't about Follicular Lymphoma?

Well, I'm excited because Idelalisib seems so promising for us -- it is in trials for Follicular Lymphoma as well, and looking good. Of course, despite the similarities between FL and CLL, they are totally different cancers, and nothing that helps one is guaranteed to help the other. But I feel good knowing that Idelalisib works for other cancers, too. Makes it seem more like the mechanism is really understood.

The other thing that seems exciting to me is that the FDA seems to be loosening up on its process a little. Not that I want them to approve things that aren't proven effective or safe, but I like the idea that they recognize that some results are just so good, and will be so helpful, that they are worth approving early. I like the idea that the FDA could consider something like that in the future for a promising Follicular Lymphoma treatment.

So, we can't pronounce Idelalisib as another arrow in the quiver just yet. But maybe the guy standing next to us at the archery range will get one soon, and we can at least shake his hand and feel good about that.

Idelalisib Approved for Follicular Lymphoma

The FDA announced yesterday that Idelalisib has been approved for treatment of three types of indolent NHL, including Follicular Lymphoma.

Also, it seems like the name is now being changed to Zydelig, to conform to the rule that all newly approved drugs have to have a Z or an X in their name, preferably both. Which stinks, because I finally learned how to spell Idelalisib without having to look it up every time.

This is excellent news. Idelalisib/Zydelig received Accelerated Approval for Follicular Lymphoma, for patients who have had at least two previous treatments. Accelerated Approval means that the approval was based on results of a phase 2 clinical trial, rather than a larger phase 3 trial (though the manufacturer will still need to conduct another trial to confirm the phase 2 results).The trial that resulted in the approval involved 123 patients with either FL or SLL (another indolent lymphoma) who were no longer being helped by Rituxan or traditional chemotherapy. The study found that 54% of Follicular Lymphoma patients responded to Idelalisib/Zydelig.

Idelalisib/Zydelig is an oral treatment, taken in pill form. It is a kinase inhibitor, targeting and stopping a protein that is responsible for cancer cells thriving and growing.

The FDA's announcement, however, makes very clear that there are some side effects associated with Idelalisib/Zydelig (there are always side effects). So while the treatment looks promising, it's still something that needs to be discussed seriously with an oncologist.

Two big take-aways from this, I think:

The first and most obvious is that we have another arrow in the quiver. Options are good, especially options that seem to work when Rituxan and chemo stop working.

The second is a little less direct, but just as important: the FDA is making serious attempts to get treatments to patients through "Breakthrough Status" and "Accelerated Approval" processes. Traditional approval for Idelalisib/Zydelig would have meant months or years of developing, recruiting, conducting, and reporting on a phase 3 study. I think the Accelerated Approval is as important as the approval itself. My guess is it won't be the last one we see in the next few years.

PI3K delta, a protein that is over-expressed in many B-cell malignancies and plays a role in the viability, proliferation and migration of these cancer cells - See more at: http://www.gilead.com/news/press-releases/2014/7/us-food-and-drug-administration-approves-gileads-zydelig-idelalisib-for-relapsed-chronic-lymphocytic-leukemia-follicular-lymphoma-and-small-lymphocytic-lymphoma#sthash.VDHyLFWM.dpuf

PI3K delta, a protein that is over-expressed in many B-cell malignancies and plays a role in the viability, proliferation and migration of these cancer cells - See more at: http://www.gilead.com/news/press-releases/2014/7/us-food-and-drug-administration-approves-gileads-zydelig-idelalisib-for-relapsed-chronic-lymphocytic-leukemia-follicular-lymphoma-and-small-lymphocytic-lymphoma#sthash.VDHyLFWM.dpuf

Even More on Idelalisib

Yesterday afternoon, Dr. Jeff Sharman posted a brief video on his blog explaining what has been going on with Idelalisib. Dr. Sharman is a specialist in CLL and NHL, and serves as medical director of hematology research for US Oncology.I've linked to his blog before; he does an excellent job of describing things for patients (who are the main audience for his blog).

I'm glad he posted the video (which was produced for Patient Power) -- I have my own speculations about what has been going on with Idelalisib over the past few days, and Dr. Sharman confirms some of my guesses, and adds a lot more information (from an expert, not just from a Cancer Nerd).

Dr. Sharman points out that there is a kind of mismatch between what we know about Idelalisib and what these new problems in trials have revealed. Why was this approved if it seems to causing infections and deaths?

As he explains, this has to do with the patients in the trials. The earlier trials involved patients who has already been treated for CLL and Follicular Lymphoma. These newer trials involved patients with untreated CLL or lightly treated FL. Since the kinase that is targeted by Idelalisib is important to immune regulation, it's possible that interfering with immune regulation early in the course of disease (say, with patients who have never been treated or were lightly treated) has a greater impact than it would on patients who are later in the course of the disease (who have had it for a while and have had a bunch of treatments already -- like those in the earlier trials that resulted in Idelalisib being approved).

Makes sense.

And so patients who were treated early in their disease, and had their immune systems affected a lot, would be more open to infections -- their immune systems can't handle certain types of viruses.

For Dr. Sharman, there is some value in these trials, even though it resulted in some very sad problems. Basically, we have a better idea of how this works -- it might be a treatment that is better suited to people who have already been heavily treated.

For people still in Idelalisib trials, or who are taking the treatment, it's worth talking to their oncologist and making sure they are being watched very closely for signs of infection. If it's working, and you're not having problems, chances are good you can stay on it.

That was a great video -- very helpful in seeing the Big Picture, especially since the FDA statement was kind of vague.

we may hear more about Idelalisib in the near future, but I think it's probably safe to say that it will remain approved and available for people who have already been treated for their Follicular Lymphoma.

The Problems with Accelerated Approvals

I've been doing a lot of reading lately about the FDA approval process and some of the things that make it problematic. There have been a couple of really interesting books published in the last year that look at this process from a couple of different angles. I may try to write about them soon. But the big theme that I find in all of my reading is that the when new treatments are up for approval, there is a delicate balance that needs to be achieved -- the safety of the treatment and its effectiveness for patients, the desire for doctors to help their patients but also to keep them safe, the need for drug companies to make a profit to justify doing research, etc. It's a very complex process.

So it was interesting to see an article in JAMA Internal Medicine a couple of weeks ago that highlighted some of these issues in ways that are similar to the books I have been reading. 

The article is called "Clinical Trials Portfolio and Regulatory History of Idelalisib in Indolent Non-Hodgkin Lymphoma."

Now, I will admit to a small obsession with Idelalisib and other PI3K inhibitors. It was about a year ago that they were pulled from the market, or voluntarily withdrawn. I wrote about this a few weeks ago. The problems came because of safety issues (more serious side effects, including patient deaths, than were expected). There were also problems with recruiting enough patients into the trials, probably because of the Covid pandemic (but also, I think, because there were at least 4 PI3K inhibitors competing for the same patients).

PI3K inhibitors fascinate me because they held so much promise (and maybe still do?), and got oncologists very excited about their possibilities. Their trial results were very good, and they worked against cancer in new ways that targeted the cancer cells while sparing many healthy cells (unlike the way chemotherapy works). 

As I've written before, several PI3K inhibitors (including Idelalisib) were given accelerated approval by the FDA. This meant that the companies could start selling the treatments, and doctors could start prescribing it, based on the results of small phase 2 clinical trials. The stipulation was that a larger phase 3 trial would be conducted to confirm the small phase 2 trial. The term "accelerated approval" is probably not completely accurate. It's more like "temporary approval." It allows the manufacturer to start earning some money on the treatment earlier than usual.

Here's the problem, as the JAMA article points out -- the issues with serious side effects were already clear, up to 6 years before the withdrawal from the market. The researchers who wrote the article looked the clinical trials involving Idelalisib. There were 31 of them. 20 of those involved indolent lymphoma (including Follicular Lymphoma). During the period after the accelerated approval, the results of 6 of those trials were available. These 6 trials were Randomized Clinical Trials, meaning they allowed a direct comparison between Idelalisib and another treatment. And in those trials, it was clear that Idelalisib had higher rates of serious side effects and patient deaths than the treatment it was being compared to.

The big problem here? It was six years later that Idealisib was withdrawn from the market, and in those 6 years, the manufacturer had $842 million in sales (though they declined over time, as problems became evident).

It's a tricky thing. Patients need new and better treatments, and businesses need incentive to spend money to develop them. Accelerated Approval from the FDA seemed to solve both problems -- promising treatments get to patients sooner, and businesses begin to make money sooner.

But, as the article's authors point out, there needs to be greater oversight during the process. It's not enough to complete the phase 3 trial and then ask for approval; there need to be steps along to way to make sure things are doing well, particularly in terms of patient safety. There isn't much incentive for a company to make trial results public after Accelerated Approval. That needs to change.

I hear lots of patient opinions about drug companies, and the kind of gray area we are all in. We need them, but we don't trust them -- I think that sums up a lot of our attitudes. Problems like this doesn't make us trust them any more, but it certainly makes us need them more.

My biggest fear with a situation like this is that it damages patient trust in other ways -- in the clinical trial process itself. If we are being asked to be a part of a trial, but problems are being "hidden," will that make fewer people want to be a part of them?

I hope that's not the case. I hope that anyone interested in a trial places their trust in the oncologist who they are working with -- someone who can explain the potential risks as well as the benefits, and pay close attention to each individual patient to make sure they are staying safe. (In the books I read about this process, that was very clear -- the oncologists working directly with patients made it a priority to protect those patients. They were kind of the heroes of the stories, even if they were in the background sometimes.)

And I hope none of you are turned off from being a part of a trial. They're the only way we find new treatments, as risky as they are, by their nature. 

Cancer is a complex thing -- within our bodies and outside of them. But like knowing all I can about my disease, I'd still rather learn about the process and know what I'm dealing with than be in the dark.

Idelalisib for Indolent/Follicular Lymphoma

Back in September, Gilead applied for FDA approval for Idelalisib for indolent lymphomas (including Follicular Lymphoma) that had stopped responding to Rituxan and to alkylating chemotherapy (including CHOP and Bendamustine). They based the application on phase 2 clinical trial results (which is early).

A couple of weeks ago, the FDA granted Idelalisib "Breakthrough Therapy" designation, meaning it has the potential to be a major advance over anything that is currently available. This ain't no fourth-generation Rituxan wannabe. This is Pulp Fiction at the Cannes Film Festival -- something very new.

The results from that phase 2 trial were published in The New England Journal of Medicine a week ago. That's important, because it means they have been peer-reviewed, with experts in the field looking over the data and the methods for collecting it, and giving their approval.

The Background section of the article is pretty interesting (and more informative than other things I've read about Idelalisib:

Idelalisib  targets something called Pl3K, a lipid kinase that helps to regulate growth and death in cells. Pl3K comes in four different types, and is present in most cells. The fourth type, known as delta, is especially present in  blood cells. Idelalisibwas created to target this particular form of Pl3K, so it is ideal for use with indolent lymphomas. It's a kinase inhibitor, which means it stops Pl3K from doing its evil job of keeping cancer cells alive when they would otherwise die.

The study was fairly small -- 125 patients -- but pretty successful.  I'm not going to get too much into methods and results (you can read on your own, all you people with two healthy shoulders), but basically, 90% of the patients had their lymph nodes shrink. the overall response rate was 57%, including 6% who had a complete response. (Not sure what the difference is between that 90% with shrunken nodes and the smaller number who were classified as "responding.") For what it's worth, the 72 Follicular Lymphoma patients in the study had a 54% response rate, which wasn't the bast, but which was decent. Maybe more important was that "responses were rapid and durable" as patients kept taking the Idelalisib. Side effects were common, though they seem manageable, and doesn't overlap with other treatments, so some combinations might be in the future.

Overall, a bunch of good news in the last month for indolent lymphoma patients. The FDA review will take place later this year; let's hope it's fast and positive, and we have another arrow in the quiver soon.

Update on Idelalisib Review

If you haven't read my previous post from yesterday (March 14), read that one first. This is an update to that post.

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UPDATE: Last night (Monday, March 14), the FDA issued a statement about Idelalisib; the manufacturer is shutting down 6 clinical trials involving patients with SLL, CLL, and indolent NHL. There statement is here (and available on their website):

FDA Alerts Healthcare Professionals About Clinical Trials with Zydelig (idelalisib) in Combination with other Cancer Medicines

The U.S. Food and Drug Administration is alerting health care professionals about reports of an increased rate of adverse events, including deaths, in clinical trials with the cancer medicine Zydelig (idelalisib) in combination with other cancer medicines.
Gilead Sciences, Inc. has confirmed that they are stopping six clinical trials in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma and indolent non-Hodgkin lymphomas. The FDA is reviewing the findings of the clinical trials and will communicate new information as necessary.
Health care professionals should be aware that Zydelig is not approved for previously untreated chronic lymphocytic leukemia.
Zydelig is currently approved by the FDA for the treatment of:

• Relapsed chronic lymphocytic leukemia, in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.
• Relapsed follicular B-cell non-Hodgkin lymphoma in patients who have received at least two prior systemic therapies.
• Relapsed small lymphocytic lymphoma in patients who have received at least two prior systemic therapies.

Patients should talk to their doctor if they have questions or concerns about Zydelig. The FDA urges health care professionals and patients to report adverse events involving Zydelig to the FDA MedWatch program.

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I'm still very curious to see what is happening here.

Clearly, the data presented enough of a problem to cause concern in both the U.S. and Europe, so something is up. The challenge, I guess, will be to determine what factor is the cause of the problem: the particular combination of treatments; the way the trials were designed, etc.

Here's my fear: Idelalisib was approved as a "breakthrough therapy" by the FDA, meaning  its approval was based on preliminary trial results -- sooner than most treatments are approved. Would the problems have been see if the Idelalisib went through a full, traditional review? Maybe. But preliminary results have to be followed up by more trials to confirm, so the Breakthrough designation doesn't mean that they get a free pass. It just mans that they get an earlier pass.

My fear, though, is that this will call into question the value of the Breakthrough designation program, which is designed to get treatments to patients sooner than they might have. That's a good thing.

But serious Adverse Effects are not good.

There are other PI3K inhibitors in trials now, too. It will be interesting to see if they get put under closer scrutiny, or if they can show that they are not dealing with the same Adverse Effects.

I'll be keeping a close eye on this situation. It could be a while before anything happens.

Idelalisib

The medical journal Blood published three articles recently on Idelalisib, formerly known as CAL 101 and as GS-1101. One dealt with the remarkable success that Idelalisib has shown on CLL; another on the somewhat less successful attempts to treat MCL; and a third that was moderately successful in treating indolent NHL, including Follicular Lymphoma. The results come from a phase I clinical trial.

Idelalisib is a kinase inhibitor (as you know if you've been paying attention to these things). It specifically targets the P13 enzyme, which B cells need to survive. So inhibiting or blocking it will kill off the cancer cells.

The indolent NHL group involved 64 patients, all of whom had already had at least one previous treatment (and some as many as 10). Because this was a phase 1 trial, it could be considered a big experiment, with researchers asking first, will it work?, and second, is it safe? As such, patients were given 8 different variations on how many (it is taken as a pill) and how much of the treatment taken.

The results were decent: 47% had a response, with one achieving a complete response. The median duration of response was a little more than 18 months, and side effects were for the most part mild to moderate.

While 47% doesn't seem all that astounding, it's important to remember that this is a phase 1 study, and that's good enough to justify a phase 2, which will be more refined than the general phase 1 study. It will likely involve a specific number and strength for the dose, based on what worked best. In addition, according to the lead researcher, given the number of previous treatments that the patients had, the results were pretty remarkable.

So we have further evidence that Idelalisib might be a keeper.We're going to hear a lot more about this treatment over the next year, I think.

Clinical Trial Stopped

Some bad news last week in The Lancet Haematology: a trial that looked at the combination of Idelalisib, Lenalidomide, and Rituxan was stopped because the side effects were just too much for patients (including some with Follicular Lymphoma). It's bad news, but not horrendous news, in my opinion.

The article is called "Safety and Tolerability of Idelalisib, Lenalidomide, and Rituximab in Relapsed and Refractory Lymphoma: The Alliance for Clinical Trials in Oncology A051201 and A051202 phase 1 Trials."

Basically, they took R-squared [Lenalidomide/Revlimid] and added Idelalisib to the mix. In theory, this should work. You have three agents that attack the cancer cells in different ways. If one or two don't do the job, then maybe the third one will.

The problem, of course, is that all three agents attack the cancer in different ways, they also all have side effects. Some are only found in one of the three agents, but some come from all three. And there's the problem.

There were 11 patients in the trial -- 8 of them had Follicular Lymphoma.(That's a very small number, but this is a phase 1 trial, so that's pretty typical). Over 28 days, patients were given Lenalidomide for 21 days, Idelalisib for all 28 days, and then had a Rituxan infusion once a week. Things seemed to go pretty well until patients received the Rituxan, and then symptoms of the side effects started to show up. The researchers stopped giving Rituxan, but a few patients continued to have symptoms. They decided at that point to stop the trial completely.

Specifically, the side effects were ALT elevation (a sign that the liver was being damaged) and rash for the Mantle Cell Lymphoma patients, and neutropenia (very low white blood cell count) and rash for the FL patients. (I know I don't talk about side effects enough when I discuss research -- I'm too focused on the positive -- but it's important to point them out here because it's the whole point of the article).

The researchers say that, obviously, this combination is too toxic to use. More broadly, they say that we need to bee more careful about the kinds of combinations that we attempt in fighting lymphoma.

A couple of observations, for what they are worth, from this non-expert:

First, I think our future as patients will continue to depend on combination treatments like this one. The whole idea just makes sense -- cancer cells seem to find ways around our ways of fighting them, so we need to keep finding new ways to fight. It's kind of like keeping mice out of your house -- you find the hole that they are coming in and block it, and then when they keep coming in, you look for another hole. Keep blocking the holes until they stop coming in.

(Unless the mice were used to help create Rituxan. Then they can come in any time they want....)

The trick, obviously, is going to be to find the right combinations -- the ones that are effective and safe. Every treatment is going to have side effects. We'll need to determine whether the side effects are worth it.

Second -- I sad this was bad news, but not horrendous news. What I mean is, this combination didn't work. But the three things that make up the combination do work. All as individual agents, and in other combinations (R-squared still gets lymphoma experts very excited, and Rituxan + Idelalisib is very effective in CLL -- no word on FL yet). It's easy to be alarmed at a headline and start to get worried about different agents, but there is still a lot to be hopeful about with these three, alone, together, and combined in other ways.

The real lesson here, though, is to thank the heroes who took part in the trial. Nothing happens without trials, and trials don't happen without patients who are willing to participate in them. So here's another reminder to think about being a participant, with another link to Lymphomation.org's page on Clinical Trials -- how to find them, how they work, why you should participate, and things to think about before you do. Good stuff.

So, bottom line -- a set-back for us, but I think something good will come from it in the end.

Idelalisib No Longer Available for Follicular Lymphoma (in the U.S.)

The maker of Idelalisib (also known as Zydelig) has announced that it will no longer offer the treatment in the U.S. for Follicular Lymphoma (and for Small Lymphocytic Leukemia).

According to the press release, the FDA's approval had been based on a phase 2 clinical trial. It was expected that a phase 3 trial (with a larger number of patients) would be conducted, and if the trial showed similar results (a 54% response for FL), then final approval would be given. Partly because of Covid, the company had problems recruiting patients for the trial. They decided that it was better to withdraw the treatment from the market for FL and SLL. 

Idelalisib has also been approved for Chronic Lymphocytic Leukemia (CLL) in the U.S, and it will remain available for patients with CLL. It will also remain available for FL patients in the E.U, the U.K., Canada, Australia, New Zealand, and Switzerland.

I say Covid is "partly" to blame because, from what I could tell, Idelalisib wasn't a very popular treatment. The sales for the first quarter of 2021 (January to March) was about $16 million. That's a lot of money, but not compared to Yescarta, the CAR-T treatment made by the same company, which had 1st quarter sales of $160 million. 

I don't think that's a coincidence. Certain treatments seem more and more to be the future of Follicular Lymphoma, and based on the excitement that I hear when I listen to Lymphoma experts, CAR-T (and lately, bi-specifics) are going to be the choice of doctors, especially for relapsed/refractory FL.

If all of this sounds familiar, it's because just over a month ago, the maker of Duvelisib also announced that it would be pulling its treatment from the U.S. market. Duvelisib and Idelalisib are both PI3K inhibitors. There were 4 available, and now there are two.

I have to say, I'm not entirely surprised. Last June, I wrote a post where I asked, are there too many inhibitors available for FL patients? All four (and another being featured at ASCO) did slightly different things. But it seems like there wasn't going to be room for all of them.

And that seems to be the case. Losing two options like this doesn't mean that they are bad treatments. If anything, it might mean that they are good treatments -- good enough that 5 different companies want to get in on the action. If an oncologist suggests one, either alone or in combination, it's probably still worth having that conversation.

It probably says more about the state of treatments overall for Follicular Lymphoma, rather than any one individual treatment.

I know I always get excited about approvals for new treatments -- or even about applications for new treatments. When one gets approved, I usually say it's "another arrow in our quiver" -- another option for treating our disease. (That's the phrase that the Lymphoma specialist used when I saw him about a week after I was diagnosed. It's stuck with me for 14 years.)

And I'll continue to get excited about new treatments being approved. But maybe we're at a point in Follicular Lymphoma research where the bar is being raised -- where the newer options (R-Squared, CAR-T, bi-specifics) are going to be so good that we'll see fewer new treatments being approved. Instead, we'll see better treatments being approved -- treatments with greater effectiveness, or fewer side effects, than what we have available now. 

If that's the case, then you won't hear me complain. I'll gladly write less if it means we have better options available to us. 

(I'll probably still write just as much.)

Something tells me this is going to be a very interesting year for FL patients. 

Follicular Lymphoma: Idelalisib / CAL 101

Gilead, the company that makes Idelalisib, has submitted an application to the FDA. They seek approval for Idelalisib for use in Indolent Lymphomas (which would include Follicular Lymphoma) in patients that have developed a resistance to Rituxan and alkylating agent chemotherapies (these would include both Cyclophosphamide, the "C" in CHOP and CVP, and Bendamustine). That covers a lot of common treatments. So, basically, if you had chemo and it stopped working, chances are pretty good that you'd be eligible for Idelalisib.

alkylating-agent-containing chemotherapyal

Idelalisib (which has also been called CAL-101 and GS-1101 at various times during its life) is a type of kinase inhibitor that blocks pathways necessary for B cells to survive. The FDA application is based mostly on results from a phase 2 trial that was reported on in June (I wrote about it here). The results were good: 125 patients, Follicular Lymphoma and other indolent lymphomas, with 53.6% achieving an overall response and 89% achieving some measure of lymph node shrinkage.

Curious, though, that they are applying based on phase 2 results; there's no indication from the press release that they are asking for accelerated approved. It's not unheard of to get approval after a phase 2, though phase 3 (which involve a larger base of patients) are more typical. I haven't seen anything on what their strategy is for "going up early," but I'm guessing it's something like "Why not? The worst they can do is say they want to see phase 3 results."

Perhaps, in its favor, is the fact that this will be the first treatment in its class to be approved. There are a whole bunch more behind it in the pipeline that work on a similar mechanism. Collectively, they really change the way we might think about treating Follicular Lymphoma.

I'm certainly hoping for a successful application. Another arrow in the quiver.

Infection Risk in FL Treatments

Interesting research published last week in the European Journal of Haematology. Not very happy, but important.

The article is called "High Risk of Infection in ‘Real-World’ Patients Receiving Ibrutinib, Idelalisib or Venetoclax for Mature B-cell Leukaemia/Lymphoma." 

The quick summary: what we know about a treatment's side effects comes from clinical trials. Once a treatment has been approved for a particular use, there seems to be less research on side effects, so what we know about them is what we learned from the trials. There might be more research on effectiveness that happens after the trials, but not a lot of side effects. 

And I understand that impulse. I have mentioned a bunch of times that I have to stop myself from focusing only on how effective a treatment is, and ignoring side effects. The numbers for effectiveness are more hopeful and happy. So I make sure to mention the side effects -- the "Adverse Events," as they are called in clinical trials. They're important. Effectiveness doesn't mean anything if a treatment does a lot of harm. As someone said to me once long ago, "You can put cancer cells in a test tube and add gasoline. The gasoline will kill the cancer cells, but do you really want to put gasoline into your body?" The point stuck with me.

So I find it very interesting when researchers go back and look at treatments after the clinical trials are all done. It's called "real world" research. A treatment might be approved based on the results of 500 patients in a phase 3 trial. And then maybe thousands more patients actually take the treatment, and the effectiveness and side effects don't match up exactly with what happened in the trial. Those 500 patients are an excellent sample, but not always completely accurate. 

And that's what this article is doing. It looks specifically at three treatments used for B Cell Lymphomas and Leukemias -- Ibrutinib, Idelalisib, and Venetoclax. And it found that patients had a greater risk of developing infections than the trial results suggested.

While these three particular treatments are used effectively for a bunch of different blood cancers, they have had mixed results for Follicular Lymphoma. Venetoclax and Ibrutinib have both been tried on their own for FL patients, and didn't do as good a job as they have done for other blood cancers like Chronic Lymphocytic Leukemia. But they do seem to work better as part of combinations (like the ViPOR combination of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid). 

Idelalisib is a different matter. It was given accelerated approval for Follicular Lymphoma based on phase 2 trial results, and then problems came up during the phase 3 trial that would confirm the smaller trials results. The company that makes Idelalisib withdrew the treatment from the market. The official reason was that they were having a hard time recruiting patients for the phase 3 trial due to Covid, but unofficially, it wasn't selling well, and the FDA was finding problems with other similar inhibitors. So to me, it's not a surprise that researchers would find more problems than the clinical trial found.

What this research found was that patients who received these three treatments developed infections at a greater rate than patients in the trials. In the small study (67 patients), 48% developed a severe infection. The median time to first infection was 5.4 months. All of that makes sense -- these treatments work by going after cancerous immune cells, but also normal immune cells, so patients are more prone to infections. 

More importantly, the researchers found that patients had more problems when they had high scores in ECOG (Eastern Cooperative Oncology Group) performance status and high CCI (Charlson Comorbidity Index) scores. Both of these tests are very common and also make sense, since they are based on traits that would show that  patient is more likely to have health problems. (You can learn more about ECOG scores here, and  CCI Scores here.)

The major point for me in all of this is to remember that all treatments have side effects, and if you're in the habit of reading about Lymphoma research (and that's probably a reason that you're here), you need to look at all of the results of research -- the bad stuff as well as the good stuff. And when it does come time to need treatment, and you have options, it's important to as the doctor about things like side effects. Quality of life matters -- maybe a less aggressive treatment with a shorter PFS is more important to you than a more aggressive one with a longer PFS, if the less aggressive one means fewer potential side effects. More questions to ask makes for a better experience.

More fun Lymphoma research coming soon. Take care of yourselves.

Follicular Lymphoma: Idelalisib

Kind of a quicky, because I'm busy with work:

A phase 2 study of  Idelalisib (formerly known as GS-1101) shows good results in patients of Follicular Lymphoma and other indolent (slow-growing) lymphomas.

The trial looked at 125 patients, focusing particularly on those who refractory to Rituxan and certain chemos. Those enrolled had a median of 4 previous treatments. (Basically, these are folks who are starting to notice the quiver is getting a little light on arrows, if I can use a comparison I'm fond of.) This is a fairly under-represented group, so it's nice to a see a trial that focuses on them.

Idelalisib is another kinase inhibitor --one of those newer treatments that targets pathways that are necessary for B cells to survive. As such, they tend to have fewer horrible side effects than traditional chemo (though are still some side effects).

In this trial, 53.6% of participants achieved a response, and it lasted just a shade under a year. 89% of patients achieved at least some shrinkage in lymph node size.

The study was led by Dr. Salles, who was featured in a video with Dr. Cheson that I posted just a few days ago, discussing this very treatment (and other topics). As Dr. Salles said then, these treatments work pretty decently on their own, and seem to also increase the effectiveness of more traditional chemo.

There are a few people in my support group who are being given Idelalisib. Not sure if they are in this trial, specifically, but they seem to be generally happy with the results.

I assume we'll be seeing more of this in the months and years to come.

Duvelisib Trial

OncLive has been producing some interesting videos lately, mostly of experts in oncology discussing recent developments in the field.

The most recent is a series of videos focusing on PI3 kinase inhibitors, featuring Dr. Ian Flinn and Dr. Jennifer Brown. You can watch all four videos in the series at the same link, though I'm mostly going to focus on Dr. Finn's discussion of Duvelisib.

First, some background (some of this is covered in the other videos in the series, and you can always  read about lots of targeted pathway treatments at Lymphomation.org).

Duvelisib is a type of Kinase Inhibitor. The other Kinase Inhibitors that get talked about a lot in Follicular Lymphpoma circles are Idelalisib and Ibrutinib. Duvelisib and Idelalisib are examples of PI3 Kinase Inhibitors, so it makes sense to look at them together (which the OncLive videos do).

In general, a protein kinase is a kind of enyzme that attaches to other proteins to allow them to help a cell function, by growing or dividing or doing its basic job. So a Kinase Inhibitor is a treatment that inhibits a Kinase from attaching to the those proteins. If you look at the Lymphomation link above, you'll see that inhibitors are part of a larger group of treatments called pathway targeting treatments -- a kinase allows the cell to perform an action, and when that action is done, it allows another action to happen, etc., etc., almost like a pathway. So if you cut off one of those actions, the rest of the pathway can't happen. Inhibit a kinase from attaching to a protein, and it messes up the rest of the cell's pathway. Do that to a cancer cell, and you keep the cancer from growing.

PI3 (short for Phosphoinositide 3) Kinase inhibitors focus on a specific part of a larger pathway known as the PI3K/AKT/mTOR pathway. Just like other pathway targeting treatments, messing with one part of this pathway will shut the whole thing down, and there are treatments that target AKT and mTOR in different stages of development. This pathway is important for a cancer cell being able to grow, feed itself, and copy itself, so messing it up will mean that the cell can't grow and divide and do the bad things that makes cancer so horrible.

But of course, nothing is easy when it comes to cancer.

In the body, proteins have different isoforms. This means when they get copied, they don't come out exactly the same. They might be pretty close to the same, but they aren't exact. This is actually a good thing, usually. It allows for protein diversity, and in evolution, diversity is a good thing.

Imagine it this way -- you make a batch of chocolate chip cookies. The first dozen come out a little crispy, so with the second batch, you take them out a minute sooner, so they are less crispy and more chewy. The third batch, you forgot about, so they stay in three minutes longer and are downright hard. Same recipe, three very different cookies. Fortunately, you have three kinds who drive you crazy by not agreeing on anything, and one likes chewy cookies, one likes crispy cookies, and one likes them hard so she can dunk them in milk. Same recipe, three different cookies, but three happy outcomes. No one complains about the cookies. Diversity is good.

Same with protein isoforms. One protein that gets copied, but with slight variations. They all came from the same source (or recipe) and they all do the same function (make your kids shut up because they aren't really hungry, just bored, because it's summer and they won't admit that they really do want to go back to school).

So, to get back to PI3 Kinase inhibitors. Naturally, they have different isoforms, known as p110 alpha, p110 beta, p110 gamma, and p110 delta. Without knowing that, someone could think they are targeting all PI3 kinase, but are really only targeting one isoform.

Fortunately, researchers are aware of the different isoforms. Idelalisib targets the p110 delta isoform, and Duvelisib both gamma and delta isoforms.


There are a bunch of other PI3 kinase inhibitors in different stages of testing, targeting differennt isoforms and different cancers, including a few more for Follicular Lymphoma.

Dr. Finn's video on Duvelisib discusses a particular phase I clinical trial that looked at single agent Duvelisib (it has been in other trials as a combination treatment with other agents). This trial looked at Duvelisib as a treatment for patients who had tried Rituxan and chemo and were no longer seeing any results from them. Early results for single-agent Duvelisib look great -- 70% Overall Response with "nearly one third" having a Complete Response.

The four videos focus in PI3 Kinase inhibitors, but they touch on lots of different treatments (Dr. Finn is excited about R squared). Worth watching.

Hope the background info helped.

Always nice to know we have some more potential arrows for our quivers.

ASCO: Idelalisib for Follicular Lymphoma

Closing out the review of ASCO with a look at a report of a phase II clinical trial for Idelalisib, the PI3Kδ inhibitor.

Idelalisib is also known as GS-1101 or CAL-101, and its job is to inhibit, or stop an enyzme that controls functions like cell growth, survival, and reproduction in cancer cells. Blocking that enzyme means stopping the cancer.


The clinical trial focused on Follicular Lymphoma patients who are heavily pre-treated, refractory to R+chemo (that is, Rituxan and chemotherapy have stopped working), specifically an alkylating agent, like what a patient would get in CHOP or Bendamustine. Basically, the trial looks at FL patients who have used up most of their options.

72 patients were involved in the trial. The results were great -- 57% of them saw their lymph nodes reduced in size by at least half.The Overall Response Rate was 56% (10 Complete Responses and 30 Partial Responses). The median response duration was 11 months overall, and 27 months for patients that had a Complete Response. Progression-free survival was 11 months, which doen't seem like a lot, but was "substantially longer" that the last treatment the patients had received (remember, this is a group that had pretty much run out of options).

So this is great news for us. A very specific arrow for a very specific quiver.  And, bigger picture -- it gives us an even better sense that kinase inhibitors, and other, newer targeted therapies, are working as well as we had hoped.

So, closing things out, ASCO wasn't about quantity for Follicular Lymphoma, but definitely about quality. I mentioned the study on Polatuzumab Vedotin in my post on Dr. Bruce Cheson's ASCO Preview, and the more I read about it, the more interesting it seems. And the R-Squared trials now underway look great, too.

Lots to keep an eye on for the future.

Copanlisib for Follicular Lymphoma

Last week (yes, I'm still catching up), the manufacturer of Copanlisib announced that it was expanding its clinical trials, with two new phase III trials for indolent lymphoma and one new phase II trial for DLBCL. This is good news (assuming enough people sign up for the trials, of course).

Lots to unpack here.

Copanlisib hasn't been in the news much, at least not the news that I have been reading.  First off, let us note that Copanlisib is a pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor. Kinase inhibitors are a type of treatment that has certainly been in the news lately for Follicular Lymphoma and other lymphomas. These are "pathway treatments" -- they don't attack the cancer cells directly, but block the pathways that help cancer cells develop, grow, and multiply. PI3K inhibitors work by blocking signalling pathways in cells. That is, before a cell can grow, it needs a signal from somewhere else down the pathway. Cancer cells get that signal, but keep on growing.  A PI3K inhibitor keeps that signal from reaching the cell. No signal, no growth. No growth, no cancer.

Now, there is another PI3K inhibitor already approved out there -- Idelalisib. From what I can tell, Idelalisib and Copanlisib will work through slightly different mechanisms, and will target slightly different pathways. Basically, kinases are proteins, and they come in different forms. Idelalisib targets the "delta" form of the protein, while Copanlisib shows activity against both the "delta" and "alpha" forms. So maybe there is a chance that they will work together, or compliment each other in some way.

Copanlisib has already shown some good activity in indolent lymphoma. At the ASH conference a few months ago, results from a phase II study showed that, in 33 patients with different types of NHL (including 16 with Follicular Lymphoma), all of whom had already been given several treatments, almost half had a response. For the Follicular Lymphoma patients, 1 had a Complete Response, 1 had an unconfirmed Complete Response, and 5 had Partial Responses, for an Overall Response of 47%. Not too bad.

Those same patients will be the target group for one of the phase III trials announced last week.

So, this is good news. Another potential arrow for the quiver, as they say -- another possible way of attacking this disease. But in a targeted manner.

Of course, we are still early in the process. As Karl from Lymphomation.org has pointed out before, we have lots of potential new treatments out there in various stages of the pipeline, and that is certainly something to cheer. But unless we get enough people who are willing to be a part of the clinical trials for those treatments, we won't really know just how effective they might be.

Options for Follicular Lymphoma

MedPageToday posted a nice piece a few days ago called "Expanding Options for Follicular Lymphoma Patients in Relapse: Studies of the Microenvironment and Immune System Spark Enthusiasm." MedPageToday is geared toward health care professionals, and this article isn't the type that reports on something new. Instead, it gives a nice summary of some of the developments in treatment options for Follicular Lymphoma patients.

And as much as love reading and writing about exciting stuff in the clinical pipeline, it's also really nice to read a basic article that describes what is available to us at the moment. It's great to see all of that good stuff in one place.

The article open with some information about Rituxan, and the recent research that shows that retreating with Rituxan at the first relapse is as effective as treating with chemo + Rituxan, or Rituxan Maintenance. It also mentions the great success that "R-Squared" (Rituxan + Revlimid) has shown in Follicular Lymphoma.


And then we get to the "expanding options" from the title:

Like Idelalisib (Zydelig), the PI3 Kinase Inhibitor. Over half of FL patients in a phase II trial had a response to Idelalisib, which prompted the FDA to approve its use for relapsed FL (again this is old news).  Interestingly, one expert says that most research on Idelalisib has focused on its effects on B cells, but he thinks there is an effect on T cells (which would help the body fight the cancer cells on its own). I look forward to seeing that research some day.

That same expert (Dr. Stephen Ansell from the Mayo Clinic) points to the disappointing results from Ibrutinib (Imbruvica), another inhibitor (this one targeting Bruton's Tyrosine Kinase, or BTK). Dr. Ansell hasn't given up hope yet, though, and he thinks Ibrutinib might work for Follicular Lymphoma by combining it with another "checkpoint" treatment (that is, not one that targets the cancer cells directly, but one that stops certain processes that the cancer cells need in order to function).

And then there are the potential treatments that will help the immune system fight off cancer on its own -- the awesome Immunotherapy treatments.

One big challenge with all of this: we might have, as the article puts it, "drugs in search of patients." In other words, we might have a bunch of treatments that seem to work, but no idea which FL patients they will work on, exactly.

So the next step is finding biomarkers -- some kind of genetic or cellular or other mark that we can identify on an individual patient, and then match up a treatment that works with that biomarker.

The other big challenge: trying to balance effectiveness of a treatment with quality of life, which has become increasingly more important. A treatment might have a high chance of working, or of working for a long time, but a patient might rather opt for a less aggressive treatment with lower chances of success, or that won't work as long, if it means fewer side effects. That's certainly an important consideration for me.

So many exciting options, but so many questions that remain.

Overall, though, I'll take those unanswered questions as long as those great researchers keep trying to find answers.

Lots to be happy and hopeful about.

Patient Power on Idelalisib/Zydelig for Follicular Lymphoma

Many thanks to Ann Erikson, who let me know that the good folks at Patient Power just posted a video discussing Idelalisib/Zydelig, and what the FDA approval means for patients with relapsed Follicular Lymphoma. I hadn't visited Patient Power in a while, so I'm glad someone else was on top of it. Ann found the video "very encouraging," and I would have to agree.

And it sounds like Dr. John Pagel, from Fred Hutchinson Cancer Center in Seattle, is also very encouraged. He is interviewed in the video by Andrew Schorr, who founded Patient Power (and who does so much to educate the cancer community).

Dr. Pagel describes Idelalisib/Zydelig as "patient friendly," fairly well-tolerated, and allowing for a relatively normal life.He calls it a "revolutionary approach."

He also is excited above the FDA's Accelerated Approval for the treatment (something I also thought was pretty significant).

Finally, and while I'm reluctant to say it, Dr. Pagel thinks a cure is not far off. "It's a great time to be a researcher," he says, and not the worst time to be a Follicular Lymphoma patient.

Thanks again, Ann.

Idelalisib: Implications

This is a few weeks old now, but it's a video of Dr. Bruce Cheson of Georgetown University, and most of you know how much I enjoy his videos.

Dr. Cheson discusses the announcement that some Idelalisib trials were being cancelled. As you can see, the usually entertaining Dr. Cheson starts out by saying "Today we have no music, we have no jokes. It is a serious discussion." And it is.

He discusses a second treatment that has had problems in its trials -- Acalabrutinib, which apparently has had success with CLL, but not with Follicular Lymphoma. I must confess, I don't know much about Acalabrutinib. It seems like it might be gone before it ever really got going enough for me to notice. It's a BTK inhibitor like Ibrutinib. That's about all I know.

The important message from Dr. Cheson comes at the end of the video. He was asked if the problems that these meant "the end for a chemo-free world." He says, "Absolutely not." There are treatments that work, and more being developed. As problems are being seen by researchers in trials, it's clear that future versions of these treatments will need to be more carefully developed and studied to try to take care of some of those problems.

Dr. Cheson has faith in the future, and that's good enough for me.

If you try to watch the video, you may be asked for a Medscape login. Medscape is great, and I recommend joining. But if you'd rather not, Dr. Cheson included a transcript of his video, which I have copied below.

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

Hello again. This is Bruce Cheson from Georgetown University Hospital and the Lombardi Comprehensive Cancer Center, speaking to you for Medscape Hematology. Today we have no music, we have no jokes. It is a serious discussion.
Last week, I was in the splendid city of Rome giving a couple of presentations at the Second Postgraduate Lymphoma Conference. I was invited by my good friend Pier Luigi Zinzani, and was asked to give two talks: (1) on Bruton tyrosine kinase (BTK) inhibitors in follicular lymphoma, and (2) on how we're getting to a chemo-free world in patients with follicular lymphoma. That's a particularly favorite topic of mine, because I think that's really the goal of treatment.
Unfortunately, [because of breaking news] I had to make some very last-minute adjustments to both of these presentations. Regarding the chemo-free world, we've had an increasing number of very exciting drugs over the past few years, and I was to talk about these various drugs and how we put them together. Then we get this announcement from Gilead Pharmaceuticals about their PI3 kinase inhibitor idelalisib, a very active drug for chronic lymphocytic leukemia (CLL) and indolent lymphomas.
There are a number of new safety signals with that drug that have halted a number of their clinical trials, particularly those in combination with other agents. There have been cases of serious toxicities and fatalities, particularly pneumocystis and cytomegalovirus (CMV) reactivation. These events tend to be more common and more severe when you combine the drug with other agents within the first 6 or so months of treatment, and in patients who are less heavily pretreated. The trials, particularly those looking at upfront therapy, are gone.
This [safety signal] is consistent with some other observations with this drug that the hepatotoxicity and the diarrhea also are more common in the upfront setting. The drug also seems to induce a neutropenia.
So yes, it's a pill, and yes, it's targeted therapy. But yes, there are adverse effects that now require close monitoring, and the company is recommending prophylaxis for pneumocystis and frequent monitoring for CMV—and if either of these events occurs, that's it for the drug for that patient.
The second event related to my talk on BTK inhibitors. There's a great new drug out there, acalabrutinib (ACP-196). Unfortunately, whereas it seems to be fabulous in CLL, [in] the trials from Acerta Pharma, [efforts to pursue indications for acalabrutinib in combination with other drugs] in follicular lymphoma and other indolent lymphomas, such as Waldenström macroglobulinemia, are now terminated, [but Acerta is still conducting single-agent studies in those disease entities because acalabrutinib is showing promising activity with minimal toxicity]. And the company states they want to focus on getting the drug approved in CLL [in personal communications to Dr Bruce Cheson, as reported March 31, 2016]. That's their main objective, and it's a laudable one, but it also suggests that perhaps the drug is not as active as we would like to have it be in follicular lymphoma and the other indolent histologies. Too bad.
Someone in the audience asked me, is that the end for the chemo-free world? I said absolutely not. We have lots of new drugs coming along, venetoclax and others, which still offer this possibility for our patients. It's just a question of being careful, of developing newer and less toxic second- and third-generation drugs, and putting them together in an intelligent and safe fashion. Even though we have a couple of these drugs on the market, they should only be put together in the context of a carefully monitored clinical trial.
Bruce Cheson, signing off for Medscape Hematology, and I look forward to speaking to you again in the near future. Thank you.

Intermediate Risk FL: One Patient's Treatment

Targeted Oncology has another short video series featuring an oncologist discussing one patient's treatment history. Like the one they did a couple of weeks ago about a patient with high risk Follicular Lymphoma, this one highlights a single patient's story. It's not supposed to be a description for how everyone in her condition should be treated, but it is interesting to see how an oncologist makes decisions.

This one features a patient with intermediate-risk FL, and the oncologist doing the describing is Dr. Peter Martin from Weill Cornell in New York City. The link will take you to the first video in the series; the others are linked to the right of the video box.

The patient is a 57 year old woman. A scan showed activity in lymph nodes near her collar bone and groin (stage 3), and a biopsy showed grade 2 FL. She also had low hemoglobin (which carries oxygen in red blood cells), making her intermediate risk.

Dr. Martin points out that the PET scan at diagnosis is valuable as a base line in case there is a suspicion of transformation later on. [That's one of those things that I like about the Targeted Oncology series -- the oncologists who do them are very good about explaining their reasoning, something our own doctors don't always do.]

The patient was treated with Bendamustine and Rituxan initially. Again Dr. Martin discusses soem of the reasoning; he considers GELF criteria, which inolves looking at "organomegalies [enlarged organs], cytopenias [low blood counts], elevated LDH [Lactic Acid Dehydrogenase, which shows possible tissue damage], and the size and number of lymph nodes [pretty sure we all know what that means]." In this patient's case, the cytopenias and fatigue were enough to say she needed to be treated early (low red blood cell count).

Dr. Martin also discusses the uses and limitations of FLIPI scores.

They might be useful in giving a  general idea of "where a patient is headed," but it doesn't say anything about an individual patient's survival or how they might react to treatment.

Again, Dr. Martin provides some reasoning behind the decision to go with B + R. Another option might be straight Rituxan. Interestingly, he says the patient's age and the fact that is probablly still working would be a factor in using Rituxan only -- minimal disruption to her Quality of Life. He also discusses other possibilities, like R-CHOP, as well as the possibility of using either Rituxan or Obinutuzumab maintenance.

Four years later, Dr. Martin saw the patient again. She was experiencing fatigue again, and a scan showed that the nodes near he groin were large again. There were no other signs of transformation, so he didn't do a biopsy. They tried R-Squared (Rituxan and Revlimid/Lenalidomide), which worked well.

Again, Dr. Martin discussed the reasoning for the decision. The patient wanted something that would put her in remission for a while, but without too intensive a treatment (again, seems like a Quality of Life issue). One thing to consider for R-squared is how long to keep it up. Dr. Martin's preference is to not use it any longer than necessary.

Two years later, the patient again needed treatment. There was more activity throughout her body, though the scan didn't show evidence of transformation. She was given Idelalisib, a PI3-kinase inhibitor. Once again, Dr. Martin discusses his reasoning for the choice -- one consideration was that the inhibitor works in ways that are different from the first two treatments, which makes sense, given that the other two types stopped working. The decision also had, again, Quality of Life considerations -- as Dr. Martin says, "Idelalisib is an oral therapy, so it’s easy to do. It requires some blood monitoring and some clinical monitoring after that. But it doesn’t require a lot of intravenous infusions, doesn’t cause hair loss, is relatively easy to administer, and is easy to take, and as long as we’re cognizant of the potential side effects and looking for them and being ready to act on them, it’s something that can be done relatively easily."


So, once again, an interesting description of one person's treatment, with a nice description of the reasoning behind all of the decisions. It won't be the same for everyone, since everyone's disease will act a little differently. But it does give us a lot to think about.


I'm hoping they do a series now on low-risk FL, and it's basically 25 minutes of the oncologist talking about how boring the office visits are since the patient is watching and waiting and they just talk about baseball instead (which is what mine were like).


No, really, there are plenty of decisions to be made even for low-grade FL -- whether to treat or watch and wait, which treatment to try, and certainly what kinds of Quality of Life factors are important to the patient.


I'm looking forward to that one.