Jamie Reno

I want to take a quick break from ASCO and EHA to write about Jamie Reno, who died in April. 

I used to write about some people as Lymphoma Rock Stars -- people who did great things for the Lymphoma community, whether they were doctors, researchers, patients, or something else. Jamie was a Lymphoma Rock Star.

I didn't find out he had died until a couple of days ago. Jamie was a long-time journalist, and his most recent job was as editor of Breaking Cancer News, which I wrote about a couple of years ago.  The folks at BCN sent out an email to their mailing list, with a really nice tribute to him, two months after he had died. From what I can tell, his family wanted to keep things kind of quiet, and there wasn't much about it online. I looked at the Living with Follicular Lymphoma Facebook page to see if there was any news there, but there wasn't. There was nothing on the discussion board/support group that helped me so much 18 years ago. I thought maybe some old-timers there might have heard something. But there wasn't anything.

I'm not criticizing the family's decision in any way. As patients, we deal with our cancer in the way that makes most sense to us. And as family's, we mourn our loved ones in the way that makes most sense. I've been in the unfortunate position to have to decide how to mourn both of my parents' deaths from cancer. 

But at the same time, Jamie Reno really was a Lymphoma Rock Star, and I feel like there should be something said about that. I never met him, didn't know him, but he was definitely a presence in my life as a Follicular Lymphoma patient.

In 2008, when I was diagnosed, if you googled Follicular Lymphoma, one of the first things that came up was Jamie Reno's book Hope Begins in the Dark. It's a collection of 50 stories from Lymphoma patients and survivors. He was a life-long journalist, writing for Newsweek for 23 years, and winning a National Magazine Award as part of the Newsweek team that wrote about 9-11. He was a cancer survivor himself. He was diagnosed with an aggressive form of FL when he was 34, and went through CHOP. He was in remission for over 2 years, and when it came back, he tried Bexxar, a RadioImmunoTherapy. It gave him 28 years of remission. At some point, he left Newsweek and devoted himself to writing about cancer. In addition to Hope Begins in the Dark, he also wrote a book called Snowman on the Pitcher's Mound, about a 10 year old boy whose mom is diagnosed with cancer. The mom character's experience with cancer kind of parallels Jamie Reno's experience with relapsing and receiving RIT.

He was a musician, too, managed to get some great musicians to play on a CD that he put out.  

With all of the stories he helped to tell about cancer, it seems like his needs to be told to the people who haven't heard it before.

Death is always hard. Even the death of someone we never met can break of a small piece of us.

But maybe that little piece that is gone can be replaced by hope. That was certainly a message that Jamie Reno seemed to want to pass along. The email that I got from Breaking Cancer News talked about how much he emphasized the "good news" about cancer -- breakthroughs in treatment, positive stories about survival and courage, and the importance of hope.

The title of his book, "hope begins in the dark," echoes a quote from the writer Anne Lamott. I honestly don't know if she said it first, or if it came from somewhere else, but here's what she said: "Hope begins in the dark, the stubborn hope that if you just show up and try to do the right thing, the dawn will come. You wait and watch and work: you don't give up."

That's a fitting message for cancer patients, and especially for those of us living with Follicular Lymphoma, who do plenty of watching and waiting and working and not giving up.

Our stories matter. As I said, much of my FL experience had Jamie Reno's story lingering over it, in very good ways. It always helps to have a model, someone who has been there and has done OK, someone who has been in the dark and found a way out.

I try to be that for other FL patients. Now you know why.   

 

EHA: Epcoritamab and R-Squared

A reader asked me a couple of weeks ago if I reviewed presentations from the EHA Congress, the annual meeting of the European Hematology Association. It's the European equivalent of the ASH meeting in the United States. It happens soon after the ASCO conference. I have written about some EHA presentations in the past, but as I told him, I sometimes have trouble accessing their abstracts. So it hasn't been something I have done on a consistent basis. EHA has some excellent research. But it's always been a matter of access.

This year, I figured out how to look at EHA abstracts. And I had some incentive -- I got many notices about a particular presentation, "CLINICALLY RELEVANT SUBGROUP ANALYSIS FROM THE RANDOMIZED PHASE 3 EPCORE FL-1 TRIAL: TREATMENT (TX) EFFECT OF EPCORITAMAB WITH LENALIDOMIDE AND RITUXIMAB (R²) IN R/R FOLLICULAR LYMPHOMA (FL)." 

The presentation is an update on the EPCORE FL -1 clinical trial. I wrote about this a few months ago. 

First, some background. Epcoritamab is a bispecific, meaning it has two mechanisms working. On one side, it attaches to a protein on the surface of the cancerous B cell, and then also attaches to a protein on a T cell, an immune cell. In this way a bispecific uses the body's immune system to treat the cancer.

The EPCORE FL-1 trial is a phase 3 trial involving 488 patients with relapsed or refractory Follicular Lymphoma. Half of the patients received R-Squared (Lenalidomide + Rituxan) and the other half received R-Squared + Epcoritamab. The earlier results from late last year, with a median follow-up of 14.8 months, showed an Overall Response rate for the Epcoritamab group of 95% (versus 79% for the R-squared group). The Complete Response Rate was 83% for Epcoritamab and 50% for R-squared. The Progression-Free Survival for the Epcoritamab group was higher, with estimated PFS of 16 months in 85.5% of that group versus 40.2% in the R-squared group. 

The updated results break down the comparison into some sub-groups to determine if the Epcoritamab combination holds up better for certain populations. What the researchers found was that Epcoritamab + R-Squared seems to work better than R-Squared alone no matter how they divided things up. 

The results were better for the Epcoritamab group regardless of the age of the patients. For patients under 70 years old, The ORR was 96% versus 78% for the R-Squared group, and the Complete Response was 84% versus 50%. In patients 70 or older, the ORR was 91% versus 81% and the CR was 79% versus 50%. 

When patients were divided into low versus intermediate/high comorbidity (with the NHL-5 scale, a measure of how other health issues like heart, lung, or kidney disease might affect survival), the Eporitamab group again did better. Those with low NHL-5 comorbidity in the Epcoritamab group had an ORR of 94% versus 76% for the R-Squared group, and a CRR of 81% versus 50%. In the NHL-5 High/intermediate group, the ORRs were 97% versus 84% and CRRs were 86% and 49%.

The same held up for patients who received one previous treatment (ORRs were 96% vs 80%, the CRRs were 87% vs 53%,) as well as two or more previous treatments (ORRs were 94% vs 78%, the CRRs were 77% vs 45%). 

All of that matters, of course, because it shows that the Epcoritamab combination will work no matter the population. One big concern for a "triplet" like this  -- a combination of three different treatments -- is that there is the potential for three times the side effects. Patients who are older, or who have other health problems, or have been weakened by multiple treatments may have more problems with a triplet. But that wasn't the case here.

One more breakdown of the data in this presentation had to do with Lenalidomide, which has the potential for dangerous side effects. As part of the study, the researchers tried different levels of Lenalidomide -- at full strength, at 70%, and at 50%. But even with less Lenalidomide, the Epcoritamab triplet did better than the R-Squared. 

So, to sum up, Epcoritamab on its own is very good. R-Squared is very good. Combined, they are all even better, without sacrificing safety. 

I still have a few more ASCO presentations that I'm sifting through. I'll try to do the same with EHA presentations as well. More to come soon.

 

ASCO: Bispecifics in the Real World

Another ASCO review. This one is for the presentation called "Real-world outcomes of bispecific antibodies in relapsed/refractory (R/R) follicular lymphoma (FL)."

A little background first. Bispecific antibodies are one of the two general types of treatments for FL that (in my opinion) Lymphma specialists are most excited about in the last few years, with the other being CAR-T. My own oncologist brings up bispecifics as a possiblity if I need treatment again.

Bispecifics work similarly to monoclonal antibodies like Rituxan or Obinutuzumab. Those treatments are able to seek out specific cancer cells by finding a protein on the surface of the cancer cell (CD20) and then destroying the cell. Most of us who have treatment have probably been given one or the other of those monoclonal antibodies. A bispecific also finds and attaches itself to a protein on the surface of an FL cell. But it has another side to it -- one that attaches itself to a T cell, an immune cell. This brings the T cell next to the cancer cell, and the T cell is able to eliminate the cancer cell.

Mosunetuzumab and Epcoritamab are currently the two bispecifics that are approved in the U.S. (and elsewhere). In this presentation, the researchers are interested in how well they work in the real world.

That phrase "real world" means something very specific in cancer research. It refers to how a treatment works after it has gone through clinical trials and been approved. Clinical trials are very limited in many ways. They are designed to put as much focus on the treatment being tested as possible. So clinical trials participants are limited in different ways, maybe by the number or types of treatments they have already received, or by comorbidities -- pre-existing health problems. If the trial designers are concerned that a treatment might cause kidney problems, for example, they won't let anyone with kidney disease into the trial, so if participants develop kidney problems, they know it was the treatment that probably did it.

"Real world" research doesn't have those restrictions. If a clinical trial uses an "ideal patient," a real world study includes everyone, even those who aren't ideal. A great treatment isn't so great if only a limited number of patients can actually use it.

This is a retroactive study, meaning the researchers didn't ask patients to use bispecifics. Instead, they looked back at records of patients who did use them to see how safe and effective they were, especially compared to the clinical trials. A total of 99 patients with Relapsed/Refractory FL were studies. 92 of them had received Mosunetuzumab and 8 received Epcoritamab (Mosunetuzumabhas been available longer). It was a diverse group by age (raging from 33 to 101 years old) and treatment history (ranging from 1 to 14 prior treatments), including 15 who had received CAR-T.

The results were very positive. They were able to collect data from 96 patients. The Overall Response Rate to a bispecific was 87%, including a Complete Response Rate of 72%.  The responses were not significantly associated with other factors like which bispecific they received, their FLIPI score, or whether or not they had received CAR-T. All of them were successful.

The Progression Free Survival rate at 12 months was 72%, and at 18 months was 56%. Overall Survival rate were 94% and 92%. PFS was not influenced by those factors like FLIPI score or CAR-T use. 

As for safety, 34% of patients had CRS (Cytokine Release Syndrome), though none were grade 3 or higher, which is the most serious levels. Only 3% of patients had ICANS (Immune Effector Cell-Associated Neurotoxicity Syndrome). Again, side effects were not assocaited with the other factors mentioned above. 

I'm leaving out some details, which you can see yourself in the abstract. But the conclusion remains the same. This retrospective study included a diverse group of patients who had received lots of previous treatments, and the two bispecifics were effective and safe for most of them, including patients who were very elderly (did you catch that one of them was 101 years old?). They held up well in the real world.

It's important confirmation for a popular and exciting treatment.

A few more ASCO reviews to come soon.

 

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.