Sunday, April 28, 2024

2024 Social Health Awards

It's that time of year again -- voting for the Social Health Awards is now taking place.

The Social Health Awards as sponsored by Health Union, and they recognize online health advocates who represent patients with a wide range of health conditions. There are 10 categories for the awards, ranging from Rookie of the Year to Lifetime Achievement Award, recognizing efforts at caregiving, using social media, working as a team, etc. I have been blessed to have been nominated many times in the past (and thanks to those of you who have nominated me), and I was fortunate enough to have been a finalist twice. 

This year, I have been nominated in three categories (these are the descriptions from the awards website):

1) "Healthcare Collaborator: The Healthcare Collaborator category is for advocates who bridge the gaps between industry stakeholders and healthcare consumers. Whether speaking at conferences, consulting with healthcare companies, or using their experience to help change the healthcare industry, these Patient Leaders are impacting the healthcare landscape."

2) "Community Cultivator: A diagnosis can be life-changing, but fortunately, so can the support from an online community. The Community Cultivator category celebrates the online communities or forums that create an inviting space for newcomers while maintaining a safe place. Whether through online support groups, live events, or forum discussions, these leaders have mastered managing, moderating, and engaging their communities all to support others."

3) "Revolutionary Researcher: The Revolutionary Researcher category aims to celebrate the patients and caregivers who refuse to let medical jargon and data slow them down! The winner of this category stays up-to-date on the latest research, treatments, and clinical trials. This winner has a knack for transforming complex information into layman's terms for the greater community."

The nomination period is actually still going, and will continue until May 3.

But also happening now, and until May 3, is the voting.  

If you are interested in voting for me, you need to go to the voting page.  If you've done this in the past, the process is a little different this year. Instead of going to my profile and voting for me there, you need to go to the pull down menu for the category on the voting page. From there, scroll down the list of names until you find me: Bob McEachern (they should be alphabetical by first name, so look under "B.")

Be aware, though, that in order to vote, you need to provide an email address, and you'll be placed on Health Union's email list. That's not a bad thing -- check out their site Blood-Cancer.com, which I write for occasionally. Lots of good stuff there. But if you'd rather not share an email address and vote, that's fine. I appreciate your support in other ways, like reading the blog.

So thanks for considering voting for me in one or all three of the categories I've been nominated for. And thanks for reading.

 

Wednesday, April 24, 2024

Treatment Options for R/R Follicular Lymphoma (video series)

The ASCO Post, a kind of newspaper for oncologists, published a video series on treating relapsed/refractory Follicular Lymphoma. If you've been reading for a while, you know how much I enjoy watching video series like this one. I like listening to experts get excited about treatment options. 

For this series, the participants are Dr. Andrew M. Evens (Rutgers University), Dr. L. Elizabeth Budde (City of Hope Medical Center), and Dr. Carla Casulo (University of Rochester). What's especially interesting about this series is that instead of talking about treatments in general, they look at case studies of specific patients. That matters -- with a disease that can look really different for different people, it's interesting to see the kinds of factors that the oncologists consider when making treatment decisions. Of course, seeing the actual patient would be even better -- knowing their goals, their families, their histories, all of the things that make them people and not just "case studies." But even the few specific clinical details that are given are better in some ways than looking at statistics from a group of 100 patients in a clinical trial.

(By the way, each of the videos includes a transcript, in case you'd rather read or need to translate.)

The first video focuses on a patient who was diagnosed with grade 1/2 Follicular Lymphoma, and had successful treatment with Bendamustine and Rituxan. But the FL returned just 8 months later, making the patient POD24 (Progression of Disease within 24 months after receiving immuno-chemotherapy). About 20% of FL patients are POD24, and POD24 patients have a statistically lower survival rate than most FL patients. Reseachers have been payin special attention to this group, trying to identify biomarkers that could signal POD24 early on (right now, there's no clear way to predict it -- you just have to wait for it to happen).  The discussion in the video talks about what POD24 is, the types of treatments available, and whether Auto Stem cell Transplants (using the patient's own stem cells, not a donor's) is still happening these days (you don't hear much about SCT anymore).

The second video discusses a patient who had successful treatment with Rituxan, followed by Rituxan maintenance. This worked for about 4 years, but then he had some leg swelling that showed a return of the FL. More importantly, he had multiple comorbidities -- other serious health issues -- that needed to be taken into account when deciding on a second-line treatment. The conversation for this video focuses on the importance of biopsies and molecular testing to determine a stage and grade for FL that has returned, and how those comorbidities influence the treatment recommendation. (I'll let you guess which treatment they recommended, then watch the video and see if you are right. I was sort of right.)

Finally, the third video looks at a patient looks at a patient who was treated with R-CHOP (a chemotherapy), and then with B-R when he relapsed (a second chemotherapy), and then presented again with grade 3 FL. This is yet another different situation, as the patient is in a high risk category and has exhausted his chemo options. If you guessed that this third-line treatment decision comes down to choosing between CAR-T and bispecifics, then give yourself a gold star for paying attention to what's going on in the world of FL.

As I said, it's an interesting series, and the focus on actual individuals really emphasizes how different this disease can be. It highlights how important it is to have conversations with your oncologist. I'll speak for myself -- I consider myself lucky to not need treatment right now, and that has given me time to stay up on what my options are. Maybe more importantly, it's given me time to let my oncologist get to know me. When the time does come for additional treatment, it won't be a case of just looking at numbers. He'll have a sense (I hope) of what matters to me, what my treatment goals are, and who I am. I think that's important.

I hope you enjoy the series.

Thursday, April 18, 2024

Is Accelerated Approval Successful?

 I know that title is a little click-baity, but I couldn't come up with something short that really captured the complexity of this issue.

The Journal of the American Medical Association published a study last week that looked at treatments that were given Accelerated Approval in the last 10 years. It's called "Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval." The question they sought to answer (and this is quoted from the article) was "What is the clinical benefit of cancer drugs granted accelerated approval, and on what basis are they converted to regular approval?" In other words, how successful are cancer drugs that are given accelerated approval?

A little background, just so we're clear on what all of this means and why its important. The issue has been on my mind a lot lately, as a couple of posts that I wrote last month would indicate.

Most treatments that get approval from the FDA use the results of a phase 3 clinical trial to provide data for the application. Phase 1 trials are usually very small, and their main purpose is to show safety -- they help determine the best dose of the treatment to be effective while being safe. Phase 2 trials focus more on effectiveness, and use a larger number of patients to show that the treatment actually works. Phase 3 trials are, ideally, randomized and double-blind, meaning the new treatment is given to half of the patients in the trial, while the other half gets the old treatment (the "standard of care" -- the one that patients would usually receive). This allows for a direct comparison between the new and the old, so the FDA can see that the new is more effective and/or safer than the old. 

With accelerated approval, the makers of a treatment can apply to have their treatment approved after the phase 2 trial. Accelerated approval is usually given for treatment classes that are brand new, allowing a potentially life-saving treatment to get to patients faster then if they went through the full trial process. This benefits patients because a treatment might get to them sooner. And it certainly benefits the maker of the treatment because they can start making money (and recouping the money they put into research) sooner. 

But part of the deal is that the clinical trial process has to continue. A "confirmatory trial" has to happen to show that the good results from the smaller phase 2 trial will actually hold up over time. If the trial is successful, then the treatment gets full approval. If not, then the treatment is withdrawn.

The JAMA article, then, wants to know just how successful those accelerated approvals are -- how many actually go on to get full approval.

The authors looked back at the 129 cancer treatments that were given accelerated approval by the FDA between 2013 and 2017, and then looked at the 46 of them that had follow-up data after 5 years. The results were not great, in terms of how many showed an improvement in survival or quality of life -- only 20 of the 46 (or 43%).

Despite that, 29 of the 46 (63%) went on to get full approval. Another 10 (22%) were withdrawn, and 7 of the (15%) were still in the confirmatory trial process.

Looking at those 29 that did get full approval, only 7 of them (24%) were shown to improve both overall survival and quality of life. Another 7 improved overall survival but not quality of life, and 6 improved quality of life but not overall survival. The remaining 9 did not improve either one.

Those number are very important, which is why I'm sharing them, but I also have to point out some limitations here. I'm not able to access the full article, so I'm not sure how they measuring "quality of life." Overall survival is easy enough to measure, but quality of life is harder, and I'm not sure every study uses the kinds of patient-reported quality of life measurements that I'm familiar with. I guess that's how they measure safety, looking at the side effects that patients experienced? That would be the standard measurement in a clinical trial. If that;s the case, I really do not like referring to it as "quality of life." That completely ignores a whole lot of things that should be included in a measurement of the quality of life. 

Aside from that, Overall Survival is a complicated measurement, too. There are certainly cancers that are so aggressive that new treatments are successful when they add months to a patient's life. Then there are others, like Follicular Lymphoma, that have OS measured in years. The measurement can be so long that the median OS hasn't been reached in 5 years. That's actually very common in FL treatment trials, which is why they use Progression Free Survival as a measurement instead. So without looking at the full article, I can't tell if they are counting something like that as improving OS or not improving OS.

This is what I meant when I said it was all kind of complex.

Ultimately, though, I'm not sure those details matter.

The authors of the study provide this conclusion: "Most cancer drugs granted accelerated approval did not demonstrate benefit in overall survival or quality of life within 5 years of accelerated approval. Patients should be clearly informed about the cancer drugs that use the accelerated approval pathway and do not end up showing benefits in patient-centered clinical outcomes."

I would hope that any conversation about treatment with an oncologist would include that information, and that any oncologist would take that into consideration before recommending it to a patient. But I also know, based on the kind of enthusiasm that lots of oncologists had for PI3K inhibitors, that they aren't going to wait for full approval before using them, and that even a preliminary OK from the FDA is good enough. And probably should be.

So, I'll ask the question again that I ask in my title -- Is Accelerated Approval Successful? 

By some measures, No, it isn't. If more than half of accelerated approvals don't result in a better experience for patients, then it seems like the system failed. On the other hand, if the goal is to get new improvements to patients more quickly, than it's a success. And if a large number don't get full approval, then that IS a success. Arguably, the system works -- the treatments that aren't doing the job don't last. If the FDA gave them early approval and then just forgot about them, that would be a problem. But the follow-up makes sure that they are as god as the smaller trial showed.

Of course, "success" isn't just about how well the system works. It's about the patients who get the treatments. Every confirmatory trial that failed means a bunch of patients who didn't get the treatment they had hoped for. And that hurts to think about. From what I can tell, a lot of the treatments get accelerated approval because they offer something that available, standard-of-care treatments can't offer. Think about something like a bi-specific. It works on cancer cells in ways that no other treatment works. If the confirmatory trial involves mostly patients who have tried everything else they could, and they have hope for this new thing that might work in a different way, then that's a success. Clinical trials are necessary, and trials need participants. 

It's all so complex. 

In the end, I think Accelerated Approval has its place, and the authors are right -- being fully informed is key to it all. Talk to your oncologist about treatments, about clinical trials, and about anything else that concerns you. (But you knew that already, you smart, informed FL patients....)


Sunday, April 14, 2024

Great Debates: Alternatives to CAR-T

There's a really interesting speaker series that happens every year in New York City called "Great Debates and Updates in Hematological Malignancies." Basically, a bunch of famous oncologists get together, two of them pick sides of a debate about blood cancer, each one speaks for a while, some others comment on what they said, and they move on to the next debate.

It's probably a little bit misleading to call them "debates." I'm not sure they really expect there to be winners and losers. It's more like they are exploring together, looking at issues that don't have definite answers, and offering there thoughts. It's really an alternative format for the kinds of "update videos" that I like to post every now and then.

Follicular Lymphoma seems like a natural fit for something like this, since there really aren't any clear answers when it comes to our disease. Usually at ASH or ASCO every year, someone makes a presentation that looks at the last 10 years or so of FL diagnoses in a database, and how the patients were treated. And the treatment choices will be all over the place -- some watch and wait, some Rituxan, some traditional chemo (some of them Bendamustine and some R-CHOP), some R-squared, plus a bunch of treatments in clinical trials. You see what I'm getting at, I'm sure. There is still no clear treatment path for FL that everyone can agree on. That's partly because FL patients present differently, but also because all of those treatments work, so oncologists just go with what they've always used.

So there's lots to debate, if two oncologists are looking to have a friendly debate.

At this year's "Great Debates" (which happened about a week ago), the FL debate feature Dr. Peter Martin of Weill Cornell and Dr. Caron Jacobson or Dana Farber. The debate centered on Relapsed FL and CAR-T. Dr. Martin's presentation was called "CAR-T Cells Should Be Rarely Used in Relapsed Follicular Lymphoma," while Dr. Jacobson's was "CAR-T Cells Should Be More Often Used in Relapsed Follicular Lymphoma." Pretty straightforward.

Unfortunately, I don't have access to Dr. Jacobson's talk, but I do have an interview with Dr. Martin, where he summarizes what he said at "Great Debates." It's an interesting talk, and worth the 5 minutes it takes to view it (or read the transcript, both of which you can find here.)

I'll give you a summary. Dr. Martin's role in this debate is to argue in favor of "all of the other treatments" besides CAR-T, which seems to me to be the easier side to take. But he focuses in particular on 3 treatment options (and remember, these are for relapsed FL, not for first treatment). Traditional chemotherapy is not one of the options -- "we're al moving beyond that," he says.

The first of the three is R-Squared, or Rituxan + Revlimid (also known as Lenalidomide). In its favor is the fact that we have data from two large trials now, so we know a lot about side effects and effectiveness. As he says, R-squared will work for between 2 and 5 years on average, and it's well-tolerated.  A good option.

Second is Tazemetostat, an EZH2 inhibitor. It works especially on B cells, keeping them from growing, which makes it very well-suited to FL. About 20% of patients have a mutation in EZH2 that makes Tazemetostat a very good option, and it has very few serious side effects. For patients who have the particualr mutation, t can be very effective, especially given the low side effects.

Finally, and "most exciting," according to Dr. Martin, are the bi-specifics. He compares them especially to PI3K inhibitors, saying bi-specifics are geared toward the same population as those who tried the PI3K inhibitors, but the bi-specifics are twice as effective. They can be tricky to administer, and their most serious side effect is Cytokine Release Syndrome. But bi-specifics are also (like Rituxan) open to combinations with other treatments, which could increase effectiveness. 

It's interesting to me that this once again comes down to bi-specifics vs. CAR-T, but that's not a surprise.

What's most important is this statement from Dr. Martin: "I think we're at a very fortunate time in the history of follicular lymphoma to have a number of excellent options."

That's absolutely true, and the most important take away from this "great debate." We do have some excellent options, and more likely on the way.

I'm going to keep an eye out for Dr. Jacobson's talk on why CAR-T should be used more often. She's great, and I'm sure it will be worth sharing. 

But for now, we can remember that we have some other options, and they're very good.

Tuesday, April 9, 2024

Cannabis and Cancer

I saw an article a few days ago that caught my attention. It's from The Guardian, written by an oncologist from Australia, and it's called "Patients keep asking if they should take cannabis for their cancer. The answer is still no."

That title -- with it's "No" at the end -- reminded me of a sign that I saw once in a doctor's office. The doctor was a pain specialist, and I was there with a loved one. The sign said, in big letters, "If you are using marijuana for any reason, WE WILL NOT TREAT YOU!"

Those are both very strong statements from doctors, and they show clearly how against cannabis use some doctors are. 

I remember asking the second doctor (the one I had taken a loved one to see) why he was against marijuana use. "Are you using it?" he asked me and my loved one. "No," we said, which was true. "Good," he replied. And that was the end of the conversation.

That doesn't seem very helpful from a doctor, especially if they have such strong feelings about it. A sign like his should open a conversation, not shut it down. The whole interaction was, unfortunately, pretty typical of this doctor.

The first doctor, the one who wrote the article linked above, is a little less dramatic about the whole thing, and I think her article is worth reading. She also has strong beliefs, but is also clear about why (there is little evidence that cannabis helps with pain, nausea, sleep, or other cancer-related problems, at least in the research that she lays out). But she also links to the ASCO document that came out about a month ago, called "Cannabis and Cannabinoids in Adults With Cancer: ASCO Guideline."

The ASCO recommendation are pretty much what the author has to say, providing a "nonjudgmental" approach to patients, because patient use of cannabis has "outpaced the research." In other words, up to 40% of cancer patients are using it, whatever the research says.

And the problem is that there is so little research. Blame this on marijuana remaining a Schedule I substance in the United States, meaning it is considered to be among the most dangerous, addictive drugs we know. As a Schedule I substance, there are sever limits on the kinds of research tat can be done on it. It's been a catch-22 for a very long time -- there isn't enough research to show that it might have benefits for people, but there can't be more research because it's considered dangerous.

An FDA panel has suggested that it should be moved to a Schedule III substance, but so far that hasn't happened.  

I'm fond of ASCO, as you all probably know, and their guidelines make sense to me. 

There is no evidence that cannabis can cure any type of cancer. That might not be the case if and when it goes through more clinical trials, but for now, there's no evidence. I would never suggest cannabis in any form be used Alternative Medicine -- in place of an approved, tested treatment for cancer. I'm not a fan of Alternative Medicines. 

But Complementary or Integrative Medicine? That's a different story. There is some evidence that some patients do get some benefit from cannabis use, whether for nausea, pain, sleep, anxiety, or other issues. If they get some benefit, and they obtain the cannabis legally, then what's the problem? Even if the positive effects are psychological rather than physical, there's a benefit there. 

I hope oncologists are open to the conversation, and are clear about the ASCO guidelines and what they say -- cannabis is not a cure-all, and it can do some good, but doesn't work for everyone and does have some side effects that need to be considered. You can say that about any substance, and any Integrative practice. 

I can't offer any experience with this -- I've never used cannabis for anything related to cancer. But I'd be very interested to hear about some of your experience, especially if it's used under a doctor's care (and it probably should be, just as your doctor should know about anything you take, from blood pressure meds vitamin D). I'd like to know if it's really as popular as research suggests, and if it really does work for people.

Share your stories if you're up for it.

 

Thursday, April 4, 2024

CAR-T 2.0?

A small pharma company announced today that it was submitting an Investigational New Drug (IND) application to the FDA for what they are calling "CAR-T 2.0," a newer, better version of CAR-T (or so they hope).

The treatment is called SynKIR-310, and the phase 1 trial will be patients with relapsed/refractory B-cell Lymphomas, including Diffuse Large B Cell lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, and Marginal Zone Lymphoma.

Their treatment includes a couple of differences when compared to current CAR-T treatments. They call theirs KIR-CAR, the "KIR" being "Killer-Cell Immunoglobin-like Receptors."  These help to regulate a type of immune cell called a Natural Killer (NK) cell. NK cells are a type of lymphocyte, like B cells (which turn cancerous in FL) and T cells (which is what CAR-T uses). NK cells work differently than B and T cells, which need exposure to a threat before they can eliminate them. Basically, B and T cells have to learn that a threat (like a virus or a bacteria) is a threat. NK cells can recognize cells that are damaged by disease (like cancer) and eliminate them, and then send signals to other cells that there is a problem. 

KIR-CAR is also different in that it targets a different type of protein than CAR-T usually does. CAR-T usually attaches itself to the CD19 protein, while KIR-CAR will attach itself to something very similar. 

The upshot of this, if all goes according to plan, is that SynKIR-310 will allow T cells to not have to work as hard as they do with CAR-T, meaning it will be effective longer than current CAR-T is (for some patients, CAR-T is very durable, but for about half, it stops working after a year or so, if it worked at all).

I say "if all goes according to plan" because, of course, this is very new. It has been effective on animal models, but this IND application will mean it will be tried on humans for the first time in a trial. If you follow clinical trials over the long term, you now that a pretty small percentage will ultimately end up in the doctor's office. 

Still, this is worth mentioning because it is a really good example of the kind of innovative research that is happening to make CAR-T even more effective than it is. It would be wonderful if this trial was successful and it moved on to bigger tests. 

Early, but definitely one to keep an eye on.