ASCO: PET Scans vs Bone Marrow Biopsies

Looking at another ASCO presentation. This one looks into whether a PET scan can do a better job of detecting disease after treatment has been given to see if there was a complete response.

The presentation is called "Effect of FDG-PET–based bone marrow assessment on prognostic accuracy compared to conventional histologic evaluation in patients with follicular lymphoma: A subanalysis of the FIL FOLL12 trial."

The research comes from the phase 3 FIL FOLL 12 clinical trial. In the trial, 189 patients received a PET scan and then either Bendamustine + Rituxan or R-CHOP. After 6 rounds of treatment, patients received another PET scan as well as a Bone Marrow Biopsy. Patients who received a negative scan (no evidence of disease) were given Rituxan maintenance. Those who had a positive scan (some disease showed up), were given a second treatment, decided on by their oncologist. 

I think it's important to point out all of those details. It's a good reminder that, no matter what a clinical trial is trying to prove, patients are taken care of. There's a plan in place whether a patient's treatment is successful or not.

This particular ASCO presentation focused on those PET scans and whether or nor they could replace a Bone Marrow Biopsy (BMB).

My guess is that most of us have had a BMB. If you're lucky enough to not know what it is, a BMB is part of the standard bunch of tests that are given at diagnosis. A BMB involves having  sample of bone marrow removed from the patient's hip. If cancer cells are present in the bone marrow, it affects staging -- FL cells in the bone marrow mean the disease is at stage 4. That often (but not always) affects treatment timing and type. But it also depends on some other factors. Bone marrow is in the center of the bone, so it takes a little work to get it out. I won't get into details. It's not a fun procedure. 

So anything that keeps a patient from getting a BMB is a good thing.  

Researchers found, in compari g the results of the post-treatment PETs and BMBs, that not only did the PET scans do as good a job in identifying disease, it actually did a better job -- 8 patients who had no evidence of disease in the BMBs did have evidence of disease on their scans.   

Perhaps more importantly, the positive PET scan had longer-term implications. Patients with a positive BMB had a 33% Five Year Progression-Free Survival (PFS). That is, about a third of them went 5 years without seeing their disease progress. However, the patients with a positive PET scan and a negative BMB had a 74% Five Year PFS, and those with a negative BMB and negative PET had a 66% 5Year PFS. In other words, patients who had disease show up on their PET scans had their disease identified earlier, and were able to get it treated earlier.

My initial reaction to this was to be happy that patients might be able to avoid a Bone Marrow Biopsy. But then I was a little skeptical -- I'm not a fan of BMBs, but I'm ever less of a fan if PET scans, given how much radiation they result in. But I thought about it some more, and I'm OK with this. The research is looking at a very specific situation -- a PET scan before and after treatment along with a BMB after treatment. Patients are going to receive a PET scan before and after treatment anyway -- there's really no better way to measure if a treatment has been successful. I'd be a little more skeptical if they were suggesting that PET scans could be used for surveillance, maybe giving a patient a scan once year or something like that. That would be a bad idea. But in this context, measuring treatment success, it makes sense. 

This is another small study, in the sense that it isn't moving us forward in terms of treatment. But it might improve the Quality if Life for some patients, and that's a great thing, too.

More ASCO reviews to come.

 

ASCO Review: Off-the-Shelf CAR-T

 As I had assumed, now that the ASCO meeting is happening, I'm seeing more press releases and articles (and soon, some videos, I'm sure) about some of the presentations. I'll look at several over the next few weeks, but I thought this one was really interesting. Keep in mind, though, that it is a very small study and only one Follicular Lymphoma patient was included.

The title is "Safety and efficacy of Azer-cel, an allogeneic CD19 CAR T for the treatment of patients with relapsed/refractory non-Hodgkin lymphoma and chronic lymphocytic leukemia not previously exposed to autologous CAR T therapy."

If you've been following FL research for even a short time, you know about CAR-T. In this treatment, a patient had T cells removed from their blood and brought to a special laboratory. T cells are a type of immune cell. The immune system can't recognize cancer cells as something that doesn't belong there, so the T cells are changed in the lab so they do recognize the cancer cells. It can be a very effective treatment for many patients. (I wrote about the whole behind-the-scenes process last month.) 

One big problem with CAR-T is that it can be very expensive. I haven't seen any recent figures, but a few years ago, the cost was close to a half million US dollars. Which really isn't surprising, since each patient is basically getting a treatment made just for them. 

So one of the problems that newer versions of CAR-T are being created are trying to solve is how to bring the cost down. And one way of doing that is to create an "allogeneic" version -- one that uses someone else's T cells, so that one sample of cells can be grown and grown and used for many patients. It would create an "off-the-self" version of CAR-T.

This presentation discusses research that is attempting to do that. The specific CAR-T is called Azercabtagene Zapreleucel, or Azer-cel. The study is a phase 1b dose escalation clinical trial. Phase 1 studies are usually small, and the focus is on safety -- figuring out how much of a treatment will be effective before it starts to do more harm than good. That's what "dose escalation" means -- they increase the dose until they find out how much is too much.

This study involves only 19 patients with many different subtypes of Lymphoma. Five had Diffuse Large B-cell Lymphoma, five had Marginal Zone Lymphoma (MZL), four had CLL/Small  Lymphocytic Lymphoma, three had Primary Central Nervous System Lymphoma (PCNSL), one had Waldenstrom Macroglobulinemia (WM), and one had Follicular Lymphoma. All of them had Relapsed/Refractory disease, so they had received at least one prior treatment. 

The results were good, with 81% (13 of 16 who were evaluated) of the patients having a response, including  31% (5 of 16) achieving a Complete Response. The FL patient was one of the 5 who had a CR.

Phase 1 trials are usually focused on safety, though the abstract didn't give too much information about safety. ICANS occurred in 7 patients (37%), with 3 Grade 1-2 events, 3 Grade 3 events, and 1 Grade 4 event.  ICANS stands for Immune Effector Cell-Associated Neurotoxicity Syndrome, where immune cells can cross into the brain. Higher grade ICANS can be very serious. Another common side effect of CAR-T, Cytokine Release Syndrome, occurred in 79% of the patients (15 of them), though there were no grade 3 or grade 4 events.

The researchers conclusion is that Azer-cel is worth studying further, given that it was effective in multiple sub-types of Lymphoma, and the side effects were manageable. 

An off-the-shelf CAR-T would indeed be a very exciting new treatment. It's very early -- years from Azer-cel making it to the doctor's office -- and only 1 FL patient has been involved so far in the study. But this isn't the only off-the-shelf CAR-T being developed, and we might very well be moving closer to this being a reality.

More ASCO stuff soon.

 

ASCO: Barriers to Treatment in R/R FL

I'm continuing with my look at ASCO abstracts. In my last post, I mentioned that that you can sort the abstract search results by "Top Rated," so I looked at the "lowest rated" abstract then. I'm going about halfway down the list this time. I could look at the top of the list, but I'm guessing those will be discussed after the meeting is over, since they are likely to be about research that someone wants to brag about.

Is it just a coincidence that "top rated" abstracts tend to look at clinical trial results and other research on things like CAR-T and bispecifics, while the lower-rated abstracts tend to be about things like survivorship? Probably just a coincidence.

This abstract is called "Bridging gaps in relapsed/refractory follicular lymphoma care: Perceived barriers to treatment and clinical trial access." It looks at the special circumstances of patients who have Relapsed or Refractory disease -- that is, their last treatment stopped working after a while, or never worked at all.

It reports the results of a focus group of 25 people. A few words about what that means. If someone wanted to get the opinions abut Follicular Lymphoma from a group of people, they could do a survey (like this one from last year). The survey was answered by 337 patients from 25 countries. It's very valuable information -- all of them answered the same questions, which makes it easy to compare answers. You get a wide range of opinions.

A focus group involves a lot fewer people. Instead of filling in an online survey, a focus group is usually in person (or maybe by Zoom). The format allows the person leading the group to ask follow-up questions. And since the participants are listening to one another's answers, it often results in conversation. Both types of gathering information -- surveys and focus groups -- are valuable. But they do different things. Surveys result in breadth, focus groups result in depth.

So this group of 25 people provides some good information. They were actually divided into two focus groups included patients with Relapsed or Refractory Follicular Lymphoma, caregivers, and patient advocacy representatives. The other was made up of " multidisciplinary healthcare professionals (HCP) involved in R/R FL care in the U.S." Six HCPs and twp patients also had interviews to go into further depth about the subjects that came up in the larger groups.

Not surprisingly, there was some overlap in the outcomes from the two groups. Also not surprisingly, there were some places where they didn't agree.

The Health Care Professionals thought a few things were very important for R/R FL patients. The first was Individualized Treatment Sequencing. FL is a heterogeneous disease -- it acts a little differently for each of us, so each of us needs an individual plan for treatment. They also valued assessment for transformation, making sure patients were following closely for any signs of transformation to a more aggressive lymphoma. They also valued newer treatments when they seemed appropriate, and the need for clinical trials. They also emphasized SDM -- Shared Decision Making, where patients have some input into which treatments they would receive. 

Patients also valued many of those things. However, patients said there were varying degrees of Shard Decision Making -- some felt empowered to make decisions, while others were given limited options. The patients also said that emotional support was inconsistent, and often they only received it when the patient or the caregiver made an effort to find it. (I assume this emotional support is something formal, like access to a therapist.) Patients also valued clinical trials, but noted "limited information for refractory disease" and unequal access to trials, though some (again) were able to gain access when they made the effort to get it. Patients also pointed to how they could have a better experience with Shared Decisions Making -- by trusting relationships with HCPs, getting better access to accurate information, and engaging with patient organizations for peer support.

The researchers conclude that while Shared Decision Making is a priority for both groups, there is a need for more intentional strategies to make it happen -- better communication, patient education, and structural support.

The good thing from research like this is that is encourages more of the work to be done by the HCPs, the hospitals and cancer centers, and other people and organizations from that end of the spectrum. In other words, the people who have knowledge need to find better ways to share that knowledge with patients. They think they are, and most are doing their best. But "intentional strategies" are important -- creating formal processes to make it happen all the time, not just when a patient or caregiver asks for it. 

That said, "intentional strategies" take time to create. And oncology tends to be habit forming -- even if a new way of supporting patients is available, sometimes doctors need a push to make it part of their routine. 

So it's still going to be important for us as patients to educate ourselves, be proactive, and make sure we are getting what we need.  

The ASCO conference starts in a coupe of days, so I expect some nice press releases and video analyses to start showing up soon. I'll be sure to share the good stuff with you when I find it.

 

ASCO Abstracts Are Here! (plus, Survivorship!)

Huzzah!

ASCO has published their abstracts! It's like Cancer Nerd Christmas!

If you have no idea what I'm talking about, ASCO is the American Society of Clinical Oncology. It's the largest professional group for oncologists in the United States. Every year in late May or early June, they have their annual meeting. It's the largest gathering of oncologists in the U.S., and it's where many researchers present their work -- results from phase 1, 2, and 3 clinical trials, theoretical work, research on cancer biology that might lead to clinical trials. This year, the meeting is taking place May 29 to June 2. 

About a week or two before the meeting, ASCO releases the abstracts -- the summaries for all of the presentations.  The people who go to the meetings use the abstracts to decide which presentations they want to hear and see, so they can more details. I have never been to an ASCO meeting -- it always comes at the worst time of year for my job. (The other major meeting for blood cancer research, ASH, comes in December, at the second worst time of year for my job. When I retire, I'm going to go to all of these cool meetings.)

The ASCO Abstracts were released yesterday, so I can finally see all of the cool new research that is being presented. Like I said -- it's Cancer Nerd Christmas.

I did a quick search on the Abstracts page for Follicular Lymphoma, and 29 presentations came up. That's a little less than in the past, and a few more may show up, but there are definitely a few that are worth paying attention to.

Over the next few weeks, I'll write about some of the abstracts tat look particularly interesting. And while the conference is happening, and in the days after it is finished, there will be lots of press releases and video commentary about the presentations that are most significant, so I'll write about those, too. It's usually about a month or so of ASCO news from here. It's all very exciting.

So I might as well start with an abstract right now: "e24130: Living after lymphoma: A retrospective study of survivorship outcomes from a tertiary cancer centre in rural India."

On the abstracts page, you can sort the results in a few different ways, but the default for me was "Top Rated." I don't know who is rating the abstracts or how they are rated, but I thought it would be interesting to go down the very bottom and see which one was apparently rated last (whatever that means).

And so we have "Living after lymphoma: A retrospective study of survivorship outcomes from a tertiary cancer centre in rural India."

If you've been reading for a while, you've picked up that the idea of "survivorship" is becoming much more important to me lately. Many cancer patients complain that they get excellent care when they are diagnosed and in treatment, but after all of that is over, when they are "finished," nobody seems to care. So there are many cancer centers that have Survivorship Clinics that help cancer survivors deal with the long-term physical, emotional, and mental challenges that come when cancer is "finished."

So this particular title, with "survivorship" as part of it, certainly caught my eye.

It looks at 100 Lymphoma patients in a cancer center in rural India who were diagnosed between 2012 and 2022. They were diagnosed with several different Lymphomas, including Diffuse Large B-cell Lymphoma (45%), Follicular Lymphoma (17%), Hodgkin Lymphoma (20%), and others (18%). Almost all were treated with some kind of chemotherapy (97%). Other treatments included radiotherapy (20%) and autologous Stem Cell Transplant (9%). The researchers collected information about the patients, including "demographics, disease characteristics, treatment exposures, metabolic parameters, endocrine function, bone health, cardiovascular events, secondary malignancies, and psychosocial outcomes."

They found a wide range of long-term issues that the patients had to deal with: Metabolic complications like obesity (40.4%), hypertension (31%), high cholesterol or triglycerides (56%), diabetes (31.1%),  hypothyroidism (8.4%) and vitamin D insufficiency or deficiency (76.5%).

Other health issues included osteopenia (37%) and osteoporosis (23%). In addition, "Two patients developed new-onset left ventricular dysfunction, three experienced cerebrovascular events, and two developed premature cataracts before the age of 50. Two patients developed tuberculosis post-treatment. Second primary malignancies occurred in two patients." Finally, "Psychosocial impact was notable, with five patients remaining unmarried and one experiencing marital disruption attributed to fear of recurrence and social stigma."

The researchers conclude that greater survivorship care is needed for patients in rural India.

I'd say that is probably true no matter where we live.

I look at that list of issues, and almost half of them apply to me as well. So I'm not sure it's a problem confined to rural India. One difference might be that I may have better access to treatment of those long-term health issues. My heart-related issues are under control because I take a handful of pills every day. 

But I have to say, I see very little research on the long-term side effects of cancer treatment. Or maybe I should label them "very long-term side effects." After that 5 year mark, there isn't much attention being paid.

I guess the attitude is "Hey, you're alive after 5 years. Of course you'll have some health issues from treatment. And there is only so much time and money available for research, so we need to put our focus elsewhere." That's true, but if nothing else, more attention paid to very long-term side effects might mean more attention is paid to Survivorship and to the resources that are already available and under-used. (Read about research on survivorship services from a couple of years ago.)

I think I'd feel better if this presenttaion wasn't at the bottom of the "Top Rated" list." 

Wasn't that a good one to start with? Lympho Bob is feeling a little salty, as the kids say. 

I'll be sure to look at the top of the "Top Rated" list soon. I'm sure it will be much more exciting, and I'll have more positive things to say.

It's still a great Cancer Nerd Christmas, and I'm ready to open some more presents. 

Tazemetostat: Official FDA Alert

The big news in my inbox this week was the official FDA Alert for Tazemetostat. 

Tazemetostat had been voluntarily pulled from the market a couple of months ago by its manufacturer after results from a trial showed that there were concerns about patients developing new cancers. The news from the FDA gives more detail about that.

Tazemetostat had been given accelerated approval by the FDA, based on results from a phase 2 trial. It is an EZH2 Inhibitor, meaning it stops or inhibits an enzyme called EZH2, controlled by the EZH2 gene, which is part of process in calls that keeps them from dying as they normally would. About 20% of Follicular Lymphoma patients are effected by this issue with EZH2, and Tazemetostat was the first treatment that specifically targeted EZH2. That was enough to have the FDA give accelerated approval, which means patients could start taking Tazemetostat outside of a trial while the larger phase 3 trial went on to confirm the results of the phase 2 trial. 

But even  when they grated accelerated approval, the FDA was aware of potential issues with secondary cancers. About 1.7% of patients in the trial had developed a new cancer.

The FDA's alert gets into more detail about this. During the phase 3 trial, the rate of new cancers went much higher, with 18 of 318 patients (about 5.7%) developing new cancers, some as soon as 7.5 months after they began treatment, though most developed them 1-3 years after beginning treatment. 

Most of the new cancwrs were Myelodysplastic Syndrome and Acute Myeloid Leukemia, though there were some other blood cancers as well. 

The phase 3 trial isn't taking new patients, but it will remain open so doctors can follow up on long-term side effects of the patients in the trial.

Obviously, there is lots of bad news all around, but most especially for the patients in the trial who developed new cancers. The rest of the patients in the trial will also have to deal with the uncertainty of long-term side effects. And the rest of us have one less treatment to rely on.

The good news, if we can still see good news, is that things were handled as well as they could be, with the trial sponsors shutting it down as soon as they could, and then making sure they are following up with the patients in the trial and making sure they are taken care of. Let's all hope they are doing OK.

I think it's very important to state, though, that this doesn't mean we shouldn't take part in clinical trials. 

It's a natural reaction to read something like this and get nervous about serious side effects. But that's going to be the case no matter what treatment we end up taking. It's worth a conversation with your oncologist about whether or not a trial is right for your situation. I talk about trials with my oncologist at least every other visit, so I know what 's available.

Trials are the only way new treatments can become available. There is no other way. I remember very early on, soon after I had been diagnosed, someone in the online support group that I belonged to said that patients who agreed to be a part of a clinical trial are "heroes." I agree. 

If you are still concerned about clinical trials, or even if you just have questions about them, the Follicular Lymphoma Foundation has a webinar coming up on Tuesday, May 26, called "What No-one tells you about clinical trials and why it matters for your care."  It's going to be an excellent webinar. Click on the link to read more about it and register. 

More coming soon. Those ASCO abstracts must be just about ripe. 

 

R-Squared: 10 Year Follow-Up

The medical journal Blood published the results of a 10 year follow-up of R-Squared. The results aren't surprising (they are positive), but it's the larger content that it more interesting to me.

The article is called "Lenalidomide plus rituximab for previously untreated advanced follicular lymphoma: the 10-year RELEVANCE trial analysis."  As a reminder: R-squared is the shirt name for the combination of Rituxan and Revlimid (also known as Lenalidomide). R-squared was the first non-chemotherapy treatment that was shown to be as effective as traditional immunochemotherapy (like R-CHOP or R-Bendamustine), though it had a different set of side effects that were just as serious. The AUGMENT trial and the MAGNIFY trial led to R-Squared being approved for FL patients who had already received treatment. 

The RELEVANCE trial involved patients who had yet not received any treatment.  The original trial was large -- 1030 patients. More importantly, it is a two-arm study, so it shows a direct comparison between patient receiving R-Squared and those receiving immunochemotherapy. In 2022, I wrote about a 6 year follow-up study.  As I said then, "The results of the study showed that R-Squared remained just as effective after 6 years as it had been up to that point. The Progression-Free Survival (showing that the disease didn't get worse after 6 years) was 60% for R-Squared and 59% for R-chemo. Overall Survival was 89% for both groups. The transformation rate (the slow-growing FL turned into a fast-growing cancer) per year was 0.68% for R-Squared and 0.45% for R-chemo, and secondary primary malignancies (patients developed a new, different cancer) was 11% for R-Squared and 13% for R-chemo. There are some other statistical comparisons as well, but they all say the same thing -- R-Squared is as effective as R-chemo, and as safe."

So would R-Squared hold up as well after 10 years? Yes it does.

The median Progression Free Survival after 10 years was 110.6 months for the R-Squared group and 102.8 months for the Immunochemotherapy group.  The rate of patients with a 10 year PFS was 46.4% for R-Squared and 46.6% for chemo. Almost identical. The median Overall Survival and the median Time to Next Treatment were not yet reached in either group. (Remember that the "median" means the middle of a group, so if the median wasn't reached, it means that more than half of the group has survived and has not yet needed treatment after 10 years). The 10 year Overall Survival rate was 82.4% for the R-Squared group and 81.1% for the chemo group. The 10 year Time to Next Treatment rates were 62.2% and 66.3%. Only 9 cases of transformation occurred (3 with R-Squared and 6 with chemo). 

Comparing the 6 year follow and the 10 year follow up, it's not surprising that numbers went down after 4 more years, but more importantly, the numbers comparing the two treatments were very similar. As the researchers say, R-Squared continues to be an alternative to immunochemotherapy for untreated FL patients.  

The researchers also said this was 10 year follow-up was always part of the plan for the study, and that it would be their final analysis.

Here's what I mean when I say it's interesting in a larger context.

A few months ago, researchers published a 15 year follow-up of R-CHOP and used some statistical analysis to show that about 40% of patients in the study were probably cured. One of the big outcomes of that article was the idea that we now have a new benchmark -- other long-term studies are going to be challenged to do the same kind of statistical analysis to determine what their cure rate was. In other words, the RELEVANCE study shows that after 10 years, there isn't a whole lot of difference between R-Squared and immunochemotherapy, in terms of effectiveness. But can R-Squared match the 40% cure?

We're not getting that information here (or in the 15 year follow-up of R-Squared in the MDACC trial that was published in February) because that wasn't part of their plan. I don't know enough about statistical analysis of clinical trials to know if a biostatistician can come in later on and look at the data for a trial and make that same kind of call. But it will be really interesting to see if that kind of analysis starts showing up at conferences like ASCO and ASH and in medical journals. I'm certainly all in favor of it. I have a complicated relationship with the word "cure" after 18 years, but more studies that use that analysis and use that word might change my mind.

In the meantime, though, it's great to see long-term data of any kind to show that we have some choices. Given our own individual circumstances, there's more than one treatment available for us that will give us a chance at a good, long Overall Survival. That's some very happy news.

Odronextamab Versus the Real World

The medical journal Leukemia and Lymphoma recently published an article about the bispecific Odronextamab called "Comparative effectiveness of odronextamab monotherapy versus real-world systemic therapies in R/R follicular lymphoma." It says good things about Odronextamab, though it's the methods for the research that I find most interesting.

Odronextamab is a bispecific. If you need a reminder, bispecifics are kind of like monoclonal antibodies like Rituxan, in that they seek out a protein (CD20) on a cancer cell. But a bispecific also seeks out a protein (CD3 for Odronextamab) on a T cell (an immune cell). So it attaches to the cancer cell on ne end, and on the immune cell that can eliminate it on the other end. Bispecifics are one of those newer treatments that oncologists get very excited about (including my own oncologist). 

Odronextamab was approved for use in Europe in 2024, though it has not yet been approved for use in the United States. 

The study described in this article is interesting because of its methodology - the way it gathers and analyzes data.  

Some more background: Clinical trials are considered most effective when they are randomized, two-arm studies. What this means is, the people running the trial will decide on criteria for the trial (which previous treatments the trial participants have received, or maybe certain health conditions). The idea is to make sure that everyone in the trial is as alike as possible, so they can be compared to one another easily. As patients sign up for the trial, they are randomly placed into two groups (the two "arms" of the study). One group receives the new treatment that is being tested. The other group receives the "standard of care" -- the treatment that they would have probably received if there was no trial, a treatment that is accepted as being the most effective available. (In Follicular Lymphoma, that's complicated, because there a whole bunch of treatments that are effective for different patients.) But the idea is, you have two groups of very similar patients, receiving two different treatments, so they can be compared easily. It's the best way to argue that one treatment is better than another.

But randomized, two-arm studies are large and expensive and take lots of time. So some clinical trials are one-arm studies instead -- everyone gets the new treatment.But then when it comes time to argue that this new treatment is better than the others, it's harder to do so, because there isn't a group already set to compare it to. So the researchers have to find a study that is kind of close, that was done sometime in the past, and compare it to that study. The problem is, it won't be an exact comparison, because unlike a two-arm study, that older study might have had different criteria. One-arm studies like this aren't considered as reliable (though there are plenty of approvals of new treatments based on one-arm studies, especially accelerated approvals).

The study in this article did something a little bit different. Instead of comparing the results of an Odronextamab trial (ELM-2, which looked at 128 patients with Relapsed/Refractory FL), it kind of created its own second arm.  The researchers looked through electronic records to find patients who were treated at cancer centers similar to those in the ELM-2 study, who were R/R, and who were "real world," meaning they weren't part of another clinical trial. "Real world" research like this is less restrictive -- no criteria that exclude certain patients. 

A small digression to help explain things. Are any of you baseball fans who love statistics?  There's a baseball statistic called WAR, or Wins Above Replacement. It looks at a whole lot of statistics for an individual player, and then compares them to the average statistics for a player who would replace them if they had to leave the team. So WAR says "This player is valuable, because if he wasn't on the team and someone else was, the team would have lost 5 more games per year." It's all very theoretical, based on statistics. But it tries to show how things would be different under different circumstances.

This study seems to do the same thing. It's saying "Odronextamab is valuable because if it was available instead of these other treatments, this is how many more patients would have been successfully treated."

The "real world" patients' records were put together in something called the FLORA study. There were 88 patients who had received a total of 100 lines of treatment. Remember, these patients weren't part of a two-arm study, they were just regular FL patients whose records were examined years after they received treatment, which they received between 2015 and 2020. They received a wide range of treatments, mostly chemotherapy and immuno-chemotherapy, but also monoclonal antibodies, BCL-2 inhibitors, Stemm Cell Transplants, radiation, and some others. 

The researchers found that, compared to the real world group, patients in the Odronextamab study did better. The Overall Response Rate was 80.5% for Odronextamab vs 52.7% for the real world group. The Complete Response Rate was 73.4% vs 33.6%. Median Progression Free Survival was 20.7 months vs 11.5 months. Time to Next Treatment was 40.4 months vs. 9.7 months. 

The researchers recognzie that there are limitations with this research. For one thing, because it looks at patients from 2015 to 2020, it doesn't include any patients who received newer treatments like CAR-T or the other bispecifics that are now available. That might make things turn out differently. And, of course, because they are "real world" patients, they may have had health issues that would have made them ineligible for the ELM-2 trial. It's not really a fair comparison.

But the main ideas are still there. Odronextamab is an effective treatment for many patients, and safe enough to have already received European approval. And just like the theoretical statistical "Wins Above Replacement" in baseball, it's possible that some of the patients in the FLORA study would have had better outcomes with Odronextamab.

It's a very interesting study. I don't think it would hold up as a way to win FDA approval, but it does illustrate how effective Odronextamab is, and how great a need there is for more effective treatments for R/R FL.

I'm still looking out for news about Odronextamab being approved by the FDA. Maybe we'll get some updated news at ASCO in a few weeks.