ASH: ZUMA-5 and CAR-T and Follicular Lymphoma

The ASH Conference is over now, but the fun keeps coming.

As I said a few weeks ago, when I started looking at ASH, I said that there wasn't a lot of excitement about the Follicular Lymphoma research, at least in the days before it started. (Sometimes, if there's something really big and important that's going to be presented, the oncologists I follow on Twitter will start talking about it.)

As it turns out, there were a few (three, actually) presentations that got people excited. I'll share them over the next few days.

The first was the presentation on the updated results for the ZUMA-5 clinical trial. ZUMA-5 is one of the trials that is testing a particular CAR-T on different blood cancers. ZUMA-1 was the trial that got CAR-T approved for use with aggressive lymphomas, including transformed FL. ZUMA-5 is a phase 2 trial that is looking at CAR-T and indolent lymphomas, including the kind of slow-growing Follicular Lymphoma that most of us are dealing with.

The first results of the ZUMA-5 trial were presented at ASCO earlier in the year. The results were very good. Zuma-5 has 94 patients with relapsed or refractory indolent (slow-growing) lymphoma, 80 of them with Follicular Lymphoma. After about a year of follow-up, 94% of patients had a Response, with 73% having a Complete Response. Of the FL patients, the response was even better -- 95% Overall Response, with 80% getting a Complete Response. The results were good enough that the makers of this CAR-T version applied for FDA approval.

Now, about 6 months later, the question was, did those results hold up? Did the responses last even longer? That's an important issue with CAR-T. Early results from ZUMA-1 showed that about 1/3 of patients had a goof long remission, about 1/3 had a response that lasted a year, and about 1/3 did not have a response at all. Later trials show longer responses. 

The ASH presentation is called "Primary Analysis of Zuma-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL)."

The trial has expanded, and these results look at 146 patients with indolent lymphomas, including 124 with Follicular Lymphoma. You can click on the link to find out more about the patients in the trial (like their age, gender, FLIPI scores, etc.). But this detail seems important --  55% of them were POD24, meaning their disease had gotten worse within 2 years of receiving immunochemotherpay, and 68% were refractory to their last treatment, meaning the cancer did not respond to the treatment.

The results were still great after 17.5 months. The Overall Response Rate for everyone in the trial was 92%, with a 76% Complete Response Rate. In patients with Follicular Lymphoma, the ORR was 94%, with an 80% CRR. The response rate was about the same for everyone, even those who were POD24 or refractory. And the response was durable -- at almost 18 months, about 62% of the patients who had a response still had that response.

Of course, the treatment came with side effects, as all treatments do. About 99% of patients had some kind of side effect, with grade 3 or greater (meaning more serious) in 86%. These included side effects that are common to blood cancer treatments these days, like nerve issues and blood count issues. About 7% has Cytokine Release Syndrome, which can be very serious. Most of the side effects were manageable enough to be taken care of by the time the results were reported, but a few serious ones remained for some patients. 

So, overall, this is great news for Follicular Lymphoma patients. This new data will obviously be considered by the FDA when they look into whether or not to approve this CAR-T for indolent R/R lymphoma patients. If results continue to hold up, we might see another option soon.

There are a couple of other interesting presentations to look at, too. Give me a few days to look into them a little more, then come back and read all about them.

ZUMA-1 CAR-T Trial

OncLive has been posting some really excellent stuff lately.

A couple of days ago, they posted a piece called "Lead ZUMA-1 Researcher Highlights CAR T CellFindings in NHL." The article is a short interview with Dr. Frederick Locke of the Moffitt Cancer center in Florida. He discusses the ZUMA-1 trial, which focused on using CAR-T against aggressive lymphomas, including DBLCL and transformed Follicular Lymphoma.

There has already been some stuff written about this trial (including the link above, which gets into the 6 month follow-up for the trial, and this on the 3 month follow-up). This interview with Dr. Locke gets into a little more detail about the study and its results. (I was hoping he would talk a little more of the transformed FL patients, specifically, but he doesn't.)

But he does highlight some great things: the very high manufacturing rate of 99% (in CAR-T treatments, a patient's T cells are removed and messed with so they learn to attack cancer cells, so almost every patient was successful in going through this process); the high Response rates (82% Overall Response, and 54% Complete Response); and the manageable, even reversible side effects (which included Cytokine Release Syndrome, where the body is overwhelmed by the sudden flood of immune cells responding to the problem) and some neurologic problems.

So while the ZUMA-1 trial isn't specifically about the FL that most of us have, it should give us hope about CAR-T in general.

Interesting interview. I recommend you read the whole thing.

Who Should Get CAR-T?

A few days ago, a video was released called "Who Should Receive CAR-T Therapy for Lymphoma."

It's a presentation by Dr. Caron Jacobson, from the Harvard Medical School and Dana-Farber Cancer Institute in Boston. She gave the presentation as part of the Great Debates and Updates in Hematalogical Malignancies virtual conference this past summer.

In the presentation, Dr. Jacobson goes through the results of some of the clinical trials for CAR-T use for lymphoma patients, as well as some "real world" studies of CAR-T that happened after it was approved by the FDA. Based on that data, she has some suggestions for which lymphoma patients might benefit from CAR-T.

I'm not going to go too deep into the data -- the video does that well, and it's fairly dense in the material presented, and a lot of packed into the 22 minute video. But I'll offer some highlights.

The message that I think Dr. Jacobson wants to get across is that CAR-T is "quite revolutionary" and more patients should be encouraged to try it. The message that I am getting is sightly less positive. More on that below.

Dr. Jacobson first looks at three trials, two of which (the Zuma-1 trial and the Transcend-CORE trial) involved patients with B-cell lymphomas. (The other involved patients with T-cell lymphomas, so I'm going to ignore that, since Follicular Lymphoma is a B cell lymphoma). Both trials involved patients with aggressive lymphomas (like transformed FL).

The Zuma-1 trial's CAR-T was Axi-cell, and 82% of patients in the trial had a Response, with 54% having a Complete Response. After 6 months, 41% maintained that Response, including 36% that has a CR.

The numbers for the Transcend-CORE trial, which used the CAR-T treatment called Liso-cel, 73% of patients had a Response, and 53% had a CR. There was not enough data to give a 6 month follow-up.

Dr. Jacobson also commented on the Zuma-5 trial, which looks at patients with Relapsed/Refractory indolent FL -- not aggressive or transformed, but just your regular old FL, the kind that most of us probably have. That data was presented at ASCO over the summer.  Results are great. After about a year of follow-up, 93% of patients had a Response, with 80% having a Complete Response. Of the FL patients in the trial, the response was even better -- 95% Overall Response, with 81% getting a Complete Response.

Those numbers stayed roughly the same in "real world" studies -- doctors who kept track of how patients were doing outside of clinical trials, after FDA approval. See the video for more on the actual studies, but the Overall Response/Complete Response for them were 70/50, 82/64, and 74/54, with one of them finding 41% of patients maintaining the response after 6 months (same as the Zuma-1 trial).

All of this sounds excellent, and it is. However, it gets trickier when we look at  toxicity -- the side effects that come with CAR-T.

In the Zuma-1 trial (the trial for aggressive FL), 93% of patients experienced Cytokine Release Syndrome, with 16% having grade 3 or higher (that is, very serious). 70% experienced neurological toxicities, or nerve issues, with 35% at grade 3 or higher. In the Transcend-CORE trial, 83% had CRS (9% grade 3 or higher), and 53% had neurological toxicities (17% grade 3 or higher).

As with all treatments, there were side effects, and sometimes very serious side effects. The good news, according to Dr. Jacobson, is that doctors have learned how to manage those side effects much better, and those numbers seem to be going down.

Dr. Jacobson also looked at data from patients who were not included in the trial. They received CAR-T, but the results weren't included in the data for lots of reasons, including that they had a "bridging therapy" -- that is, in between the time their T cells were collected and the time they were put back into their bodies, they received another treatment. This makes sense to not include them -- they got something "extra" that might have messed with showing how well the CAR-T worked. 

Those patients who received a bridging therapy were tracked anyway, and the data shows that the CAR-T didn't work as well for them, though it worked better than lots of other treatments. This might have been because their disease was already very far along, and the CAR-T was getting to them too late to hep as much as it could have.

That's really important information to have.

So, based on all of the data, which lymphoma patients should get CAR-T?

Well, CAR-T gave a durable remission (one that lasted longer than 6 months) to about 41% of patients with aggressive lymphomas. Among the reasons it didn't work? Patients has elevated LDH (the disease was behaving aggressively) or had co-morbidities (other health issues that might have influenced the outcome). 

So it seems like CAR-T works well for many patients with aggressive FL, but not too aggressive or too advanced. 

And for patients in the Zuma-5 trial (relapsed/refractory FL), 83% had a response that remained after 15 months. Longer follow-ups and a larger study are necessary, but it seems kind of intuitive here -- CAR-T works better on disease that isn't too aggressive, so maybe indolent, slow-growing FL is an even better target than aggressive FL? [That's a complete guess by me, someone who, I should remind you, is not a doctor or a cancer researcher.]

Dr. Jacobson is calling for more "real world" study of CAR-T, beyond trials, because trials can sometimes be too restrictive. That makes sense -- to compare patient responses accurately, you need clinical trial participants to be as alike as possible. But outside of a trial, after a treatment has been approved, it's easier to pay attention to other variables. Expanding access makes a lot of sense.

OK, so my take on all of this (again, recognizing that I am not an expert, just a patient who reads a lot):

I agree with Dr. Jacobson that CAR-T is "quite revolutionary," and has the potential to really change things for Follicular Lymphoma patients. I look forward to seeing what the FDA thinks about CAR-T for R/R FL patients, those with less-aggressive disease. I know my oncologist s excited about this, too, and thinks it could be a game-changer for FL.

However, we can't ignore a bunch of things: there needs to be more long-term follow-up for the Zuma-5 trial. Side effects of CAR-T, while becoming more manageable, can still be very serious. CAR-T is really expensive, and some health insurers may not like the idea of paying almost a half-million dollars for a treatment when cheaper options exist.

I'm saying this from a patient advocate perspective. I see lots of patients online who think CAR-T will solve all of our problems. And you know, it just might. But we have lots of hurdles to overcome until then. It might not work for everyone, it might not remain working for everyone, and it might not be available to everyone. 

That said, there is lots to be excited about, if we can keep a long-term perspective on things. 

(And since I plan to be around for a very long time, I think I can do that. I hope you can, too.)

 

CAR-T Approved for Lymphoma

More good news for us -- the FDA has approved a CAR-T treatment for some Follicular Lymphoma patients.

(As usual, when it comes to CAR-T news, Ben beat me to the news. I just learned that he is a fan of the New York Yankees -- rivals to my beloved Boston Red Sox. I still like him anyway, and I'll keep sending you to his blog for everything you want to know about CAR-T and Lymphoma.)

The treatment is called axicabtagene ciloleucel, or axi-cel, though it will probably known to patients as Yescarta (to help you remember: Yes! CAR-T! Ahhhhhh!). The approval came from the results of the ZUMA-1 clinical trial, which involved patients with refractory aggressive B cell lymphomas.

That's important to remember. For now, anyway, the approval is for a very specific group of Follicular Lymphoma patients -- those with Transformed FL. There are other types of aggressive B cell lymphomas, too, who meet the approval criteria. But it's a big step for all lymphomas.

As a reminder, CAR-T stands for Chimeric Antigen Receptor T cell therapy. In the procedure, a patient has T cells removed from her blood. T cells are a type of white blood cell, part of the immune system, whose job is to attack invaders like viruses and bacteria. But they don't attack cancer cells. With CAR-T, after the T cells are removed, they are genetically engineered so that, when they are put back into the patient, they do recognize the cancer cells as invaders, and they attack. T cells have a memory, so if the cancer cells come back, they should be able to find them and attack again.

The ZUMA-1 trial involved 101 patients with several types of aggressive B cells lymphomas, including Transformed FL. The results were great -- 82% had a Response, including 54% who had a Complete Response. Six months after treatment, 36% were still in remission.

There are some side effects, of course, though researchers are looking into ways to recognize the most dangerous ones early and control them.

But there may be some other problems with this treatment (which I have seen coming up since the approval news).

The first will be the cost. This is an expensive treatment -- about $373,000. Granted, it's a personalized treatment -- each patient will have her own cells removed, manipulated, and put back, so it's not like it can be manufactured in large quantities. But it's still a lot of money.

The second will be the limited number of patients who have conditions that it has been approved for. It's pretty clear that only certain patients are approved for this (as is the case with any FDA approval). But Dr. John Leonard had a good point on Twitter last night. He said "I expect MDs to spend much more time explaining to lymphoma patients why they are not CAR-T candidates than managing the very few who are." This is likely to get a lot of attention (which it deserves), but won't be able to help a lot of patients -- yet. The manufacturer is developing CAR-T treatments for other types of solid cancer. The ZUMA-2 trial is looking at this treatment in Mantle Cell Lymphoma patients. ZUMA-3 is for Acute Lymphoblastic Leukemia patients.

It keeps going. ZUMA-5 is the trial for indolent (slow-growing) lymphoma patients, like those who have Follicular Lymphoma. It will look at 50 patients with indolent lymphoma whose disease has relapsed within two years of initial treatment, or had a second (or greater) treatment stop working, or who relapsed after a transplant. The first patient to get treatment in that trial got it in August.

We have a lot to look forward to.

(And I don't just mean next spring, when baseball starts up again for some of us.)

CAR-T

A couple of items related to CAR-T that are a little bit older, but worth looking at:

First, the online magazine CureToday has an article on CAR-T, specifically the ZUMA-1 trial that was reported on at the ASH conference in December, and in the journal Blood.

The article described the results from the ZUMA-1 trial, which looked at CAR-T in patients with aggressive lymphomas, mostly Diffuse Large B Cell Lymphoma (which is why I didn't write about it earlier), but also transformed Follicular Lymphoma (which is why I'm becoming aware of it now). I'll let you read the articles yourself, but basically, the patients were given a CAR-T treatment called KTE-C19, which targets lymphoma cells that have the CD19 protein on their surface. With a CAR-T treatment, the patient's T-cells (a kind of immune cell) are removed from the body, changed so that they recognize the cells with CD19, and then put back into the patient's body, where they hunt down the bad guys.(Lymphomation.org updated their section on CAR-T about a week ago; you can find some nice links there to find out more about the treatment.)

For cohort 1, the DLBCL patients, the results were excellent -- about 76% of patients (51 patients overall) had a response. Just as  importantly, the "manufacturing" process was successful, with 99% of patients being able to get their T cells changed and put back into their bodies. The average time for patients to receive their changes T cells was about 17 days, which is important because they were not all st the same site. And the CAR-T cells expanded within 14 days to the point where there were enough of them floating around to be able to do their job, the way naturally-occurring T cells do. So, lots of successes.

Cohort 2 included the transformed Follicular Lymphoma patients, and was much smaller -- 6 patients total, 3 of them with transformed FL. But the results were just as good. All 6 patients had a Complete Response, and all were still in complete remission after a median of 3 months of follow-up.

Now, 3 patients measured over 3 months is enough to give us some hope, but certainly not enough to make us think we have The Answer. This trial will continue, and I'm sure we all look forward to long-term results with a larger population.

Which brings me to another article: "Immunotherapy Cancer ‘Cure’ Headlines Distract from Fascinating Science." This was posted in the comments about a week ago by a reader named Popplepot (great name!) and it's worth revisiting. It was published about a year ago in the Science Blog published by the organization Cancer Research UK, soon after the first results from a CAR-T trial. The results were fantastic, and some of the experts commenting on it said things like "CAR-T might lead to a cure some day." Media reports heard the word "cure" and that became the focus, leaving out that the experts said "might" and "some day." The article reminds us of what makes CAR-T so fascinating (and it really is fascinating, given that it overcomes the basic problem with cancer -- why doesn't the body recognize cancer cells as invaders?).

But the Cancer Research UK article also makes us aware of some of the problems with early CAR-T trials -- they are small, and they also point to some nasty side effects (which resulted in a couple of deaths of patients).

So it's a good reminder for all of us to pay attention to some of the problems that come with new treatments. I know I'm guilty of this. I'm naturally upbeat and positive, so I ignore some of the negatives that come with reports of new treatments and clinical trial results. I'm working on it.

We're going to see more and more CAR-T results, I'm sure. Which reminds me of another reader's recent comments. William May, whose wife has had great success with CAR-T, was expecting the recent OncLive Peer Exchange video series to address CAR-T. It looks like they've moved on from Follicular Lymphoma treatments to CLL treatments, and no mention of CAR-T. I share your disappointment, William.

But that's OK. As I said, there will be plenty of stuff to read about CAR-T in the months and years to come. Looking forward to it.

(And thanks, Popplepot and William, for you comments.)

CAR-T versus Immunotherapies in Lymphoma

ASCO Post has another video from the 2021 Pan Pacific Lymphoma Conference took place in Hawaii last month. This is a discussion between Lymphoma two experts, Dr. Bruce Cheson and Dr. Stephen Ansell. (If you've been reading a while, you now how fond I am of Dr. Cheson.) 

The video clip is called "Bruce D. Cheson, MD, and Stephen M. Ansell, MD, PhD, on Non-Hodgkin and Follicular Lymphomas: Integrating Non–CAR T-Based Treatments." 

Basically, as Dr. Ansell says, the Lymphoma treatment landscape seems to be about "drugs versus cells." On the one hand, there is lots of excitement about CAR-T (that's the "cells" part of this discussion), but also lots of alternatives that are worth being excited about, too (the "drugs" part).

Dr. Ansell points out that Dr. Cheson has spent lots of his long career as a cancer researcher looking at Immunotherapies and other non-chemotherapy options for lymphoma. He asks, where is the place for CAR-T in all of that?

Dr. Cheson points out some of the problems he sees with trying to make CAR-T the default treatment for lymphoma. For one thing, there us geography. There are very few CAR-T treatment centers in the United States that are easy to get to for most people. (He says about 75% of the patients in the U.S. would have a hard time traveling to a CAR-T center). It's also expensive. And while the data about its effectiveness looks good, it's worth taking a closer look.

For example, for patients who are not eligible for clinical trials, the numbers show that CAR-T is about half as effective as for people who are in clinical trials. (To make that clear: sometimes trials will reject patients who have health issues that might mess with the data. Someone might have heart problems, and if they died of a heart issue during the trial, it still cunts toward the Overall Survival statistics for the trial, since OS measures overall survival, not survival related to cancer. So, ironically, healthy people sometimes have an easier time getting into trials, especially phase 2 and 3 trials.)

Dr. Ansell points out that this is probably true of any treatment, not just CAR-T. In the real world, people have health issues that might make a treatment less effective.

Dr. Cheson then turns to the ZUMA-1 trial to make his point about drugs versus cells. The ZUMA-1 trial was the clinical trial that resulted in the first CAR-T approval for aggressive lymphomas. As great as the results were, Dr. Cheson points out the the 5 year Progression Free Survival for that trial was about 31%, and the 4 year PFS was 35%. Still good numbers. But a different treatment combination (a "drug"), Tafasitamab + Lenalidomide, had a very similar (34%) PFS at 4 years. For Dr. Cheson, that drug combo would be a much easier choice for many patients -- a monoclonal antibody and a daily pill, instead of travel to a CAR-T center and great expense for the "cell" treatment.

(If you're not familiar with the combo, Tafasitamab/Lenalidomide was approved for relapsed or refractory diffuse large B-cell lymphoma, including transformed FL, last summer. It's in a trial for Follicular Lymphoma, but no results yet.)

Dr. Cheson admits that, if a patients came to him very excited about CAR-T, was willing and able to travel and afford the treatment, he would certainly recommend it. He's not anti-CAR-T by any means. But he also thinks that a patient in that situation would be likely to do just as well with the other combo, without the hassle. 

He also mentions that there are a number of other promising treatments in the pipeline that may challenge CAR-T, including several bispecifics.

The upside to it all is that, as both of these experts agree, things are evolving fast -- there are lots of new and exciting treatments coming our way. We're still learning about the genetics of Follicular Lymphoma, and the more we learn, the more researchers will be able to target those cancer cells effectively.

As much as they seem to be "debating" these two choices, they also are clear that both are great choices for certain patients, and we'll have more great choices in the future.

I'll add this -- with the choices we have, and knowing that some will work better than others for certain patients, it's important to get second opinions when we can, especially from lymphoma experts. General oncologists can be great, but a specialist might see something that makes them think that a newer treatment might be especially effective, something a general oncologist might miss.

Lots to be hopeful for. Watch the video if you can (and, again, sorry -- there's no transcript for translating. But you might enjoy the Hawaiian music at the beginning, anyway).

CAR-T for Transformed FL Gets Priority Review from FDA

The FDA has granted a faster-than-usual review for yet another Follicular Lymphoma treatment. This one is for KTE-C19, a type of CAR-T therapy, and it is for transformed Follicular Lymphoma, as well as Diffuse Large B Cell Lymphoma (DLBCL) and Primary Mediastinal B Cell Lymphoma (PMBCL).

(We're taking a quick break from ASCO Previews for this one. The review is based on results that were presented at a different convention -- the AACR last month. The results come from the phase 2 ZUMA-1 trial, though a few other different aspects of that trial will be discussed at ASCO.)

CAR-T therapies, in general, involve removing T cells from the patient. T cells are part of the immune system, and their job is to find invaders (like cancer cells) and get rid of them. The problem is, T cells can't recognize cancer cells. So after the T cells are removed, they are changed so they will recognize the cancer cells, and then they are put back into the patient so they can do their job.

Now, KTE-C19 works the same way. It gets its name from its target: the protein called CD19, which appears on the surface of the cancer cells being targeted (and lots of other cells). When those new, changed T cells find the cancer cells, they destroy them, the way they were supposed to.

The Zuma-1 trial looked at two groups of patients, one of them including transformed FL patients. Out of 101 total patients, 24 of them had transformed FL or another type of lymphoma. In that group, the Overall Response rate was 83%, and the Complete Response rate was 71%. After 8.7 months, the OR rate remained high -- 67%, and the CR stayed at 61%.

Patients in the trial were chemorefractory, meaning chemotherapy was no longer working for them. They had had a median of 3 treatments before the trial.

Side effects included things like anemia, decreased white blood cell counts of different types. Several patients had Cytokine Release Syndrome, which occurs when the body is overwhelmed with an immune response. There were 4 fatalities during the trial, 3 of them related to the treatment. Most of the  non-fatal side effects were reversed within a month.

Based on these results, the FDA is granting Priority Review (as it did with Copanlisib earlier this month).  This means that the FDA plans to take action on approval within 6 months, and that it considers the treatment important enough (and doing something that other treatments aren't doing) to speed it along a few months early.

If this is approved, it will give us another tool for transformed Follicular Lymphoma -- we can never have too many.

CAR-T is definitely hot this year at ASCO, with trials and experiments targeting a bunch of different cancers. I know there are a few folks who read regularly who have some experience with it, and who are very excited about CAR-T. Let's hope this one continues to give us all something else to be excited about.

anemia (43%), neutropenia (39%), decreased neutrophil count (32%), febrile neutropenia (31%), decreased white blood cell count (29%), thrombocytopenia (24%), encephalopathy (21%), and decreased lymphocyte count (20%). - See more at: http://www.targetedonc.com/news/ktec19-granted-priority-review-by-fda-for-nonhodgkin-lymphoma#sthash.schjRozT.dpuf

The 8.7-month ORR rate was 67 percent, with a CR rate of 63 percent. - See more at: http://www.curetoday.com/articles/agent-granted-priority-review-to-treat-nonhodgkin-lymphoma#sthash.V9EN38YB.dpuf

2020: The Lympho Bob Year in Review

This is probably my last post of 2020, so I'll use it to first say Goodbye to a pretty bad year. 

I don't need to tell you why it's bad. So much worry and anxiety. Poor health for many of us (I added a new health issue my list this year. It's not cancer-related. I'm not going to get into it.) Loss of loved ones for some of us. Loss of Quality of Life for all of us, with nowhere to go and no one to see. A lot of that is likely to continue, for a few more months, anyway.

But you know me -- I don't dwell on the bad stuff for long. Hope, even a little bit of hope, always shines through.

So in looking back at a bad year, I want to focus on the good stuff.

Here are my five biggest Follicular Lymphoma stories from 2020. They're not all completely great, but I can find some happy hopeful stuff in there somewhere.   

#5: Covid-19

Like I said, it's not all happy news. I couldn't ignore this, given the way it changed our lives this year. But I won't put it any higher than #5 on this list, either. 

Looking back on the blog, I started writing about Covid back in March. I really didn't have a lot to say about it, because so much was unknown, other than how it was making me feel. We got a little bit of guidance early on, but there was still so much unknown.

And there's still a lot we don't know, especially about how a vaccine will affect Follicular Lymphoma patients -- those who are immuno-compromised because they are currently in treatment, or who recently had treatment, or even whose immune systems have been affected by treatment long ago. No real answers. Maybe we'll get more information as more people are vaccinated and we have more data. I see FL patients online debating this, with some saying their oncologists think they should hold off and others thinking they should get it as soon as possible. Everyone's situation is different. Trust your doctor's advice.

But find some hope in the vaccine, even if you can't get it right away. Trust science. Encourage others to get it. Hang in there. We'll get through this.

 

#4: R-Squared

R-Squared is the combination of Rituxan and Revlimid (which is also known as Ledalidomide). It made news in 2019 when it was approved by the FDA for use on previously treated Follicular Lymphoma patients. It was an important approval because it showed that a non-chemotherapy treatment could be as effective as traditional chemo. Side effects were different, but not better or worse. 

The big news for R-squared in 2020 was that it was also shown to be effective in FL patients who have not yet received treatment. An ASCO presentation on Complete Metabolic Responses confirmed that untreated FL patients did very well with R-Squared. 

But what really puts it on the list is just how excited Lymphoma specialists are about it. I like to post articles and videos of experts kind of summing up what we know about Follicular Lymphoma, and R-Squared is always something they talk about, whether for the approval for Relapsed or Refractory FL, or the future approval for untreated FL. I don't know of any attempt to seek FDA approval  for untreated FL right now, but my guess is that it will come in the next couple of years. We're going to keep hearing about this for a while.

 

#3: Tazemetostat

Tazemetostat was approved by the FDA in June (as far as I know, it is still in trials in other parts of the world) for two groups of Follicular Lymphoma patients. The first is those with an EZH2 gene mutation. The EZH2 gene is important in telling cells that they are supposed to die, so a mutation mans those cells keep on growing and living, which is of course how cancer develops. Tazemetostat is an EZH2 inhibitor, meaning it stop EZH2 from keeping cancer cells alive. 

The other group is a little larger and less specific -- FL patients who do not have any other alternatives. It's good that they have an approved treatment to try, even if they don't have the EZH2 gene mutation. 

This one is really interesting to me. Lymphoma experts are very excited about it. But only about 25% of FL patients have the EZH2 mutation, and about 69% of patients had a response. To me, those aren't really spectacular numbers, at least compared to some other treatments.

On the other hand, those 25% of FL patients have a really good chance of being helped, and if I was one of that group, I'd want the option. 

I also think that, like many inhibitors, Tazemetostat may end up having a life as part of a combination therapy, along with one or more other treatments. 

But, really, it's the excitement from Lymphoma experts that puts this on the list. If they're excited, then I'm excited, too.

 

#2: CAR-T: ZUMA-5

There has been a whole lot of news about CAR-T for a few years now (see the CAR-T and Follicular Non-Hodgkin's Lymphoma blog for more up-to-date info -- I can't keep up with them).

And there's too much CAR-T news from 2020 to mention here, so I'll focus on what I see as the Big News, and what, once again, seemed to get experts so excited -- the ZUMA-5 trial.

A couple of different CAR-T treatments have already been approved for aggressive lymphomas, including Transformed Follicular Lymphoma. The ZUMA-5 trial focuses on indolent lymphomas -- the kind of slow-growing, less aggressive FL that many of us live with (including me). The phase 2 trial involves a fairly small number of Follicular Lymphoma patients (80), but the results have been very positive, with 94% having a response, including 73% with a Complete Response.

This is, once again, one of those treatments/trials that experts are very excited about. ZUMA-5 is a phase 2 trial, so we're probably not going to see this approved very soon (though, who knows? The makers may give it a shot). With numbers like those, it seems pretty likely to be approved. We're looking forward to that.

#1: Survival

In some ways, "survival" should be #1 on the 2020 list because we've all survived it. It's a low bar -- "I made it out alive" -- but I think it's an OK one in a year like this.

But that's not really why I put it at #1.

Looking back at what I wrote this year in the blog, I see a bunch of research on survival in Follicular Lymphoma.

Trends in Treatment and Survival in Follicular Lymphoma.

 

New Information on FL Survival.

 

Improved Lymphoma Survival Over 20 Years.

 

Plus a couple more articles with advice on how FL patients should think about their post-treatment lives. 

 

The overall message in all of this is the same --

 

Follicular Lymphoma patients are living longer lives.

 

Treatments are getting better. Newer treatments are allowing patients to live with a better Quality of Life. When I was diagnosed in 2008, the median overall survival for FL patients was still considered to be 8-10 years. Most research these days that looks at long-term follow-up of FL patients hasn't even reached a median OS yet. Patients are living too long to measure it. But many experts guess that it's about 18-20 years. 

 

How great is that?

 

There have been enough reminders this year that survival has to be #1. Not just because we made it through this tough year. But because it's getting easier for more FL patients to live longer and better lives.

 

We made it through this year. We'll make it through the tough few months at the start of next year, and we'll move beyond it. Remain hopeful. That's not just an empty saying. There are so many reasons for hope.

 

Thanks again for being with me during this tough year. I look forward to sharing more with you in 2021.

ZUMA-5 Trial: Car-T for FL

The ASCO Post, a newsletter for the American Society for Clinical Oncology, has a nice piece on the ZUMA-5 trial. ZUMA-5 is a clinical trial that looks at CAR-T for indolent lymphoma, particularly Follicular Lymphoma.  It's worth reading. 

Data from ZUMA-5 was presented at the ASH conference in December, and it was very good news. This article doesn't present any new data, but it does go into a lot more detail than the ASH abstract gave.

Much of the commentary in the article comes from Dr. Caron Jacobson of the Dana-Farber Cancer Institute in Boston.

As I wrote about in my last post, CAR-T has had some success in more aggressive blood cancers like Diffuse Large B Cell Lymphoma and transformed Follicular Lymphoma. There are three different versions of CAR-T that have been approved by the FDA for these aggressive lymphomas. They are also in trials for use on indolent, slow-growing lymphomas, like the Follicular Lymphoma that most of us are dealing with. The ZUMA-5 trial is one of them.

The phase II trial 146 patients, including 124 with Follicular Lymphoma. The patients were first given conditioning with Fludarabine and Cyclophosphamide, two chemotherapy agents (Cyclophosphamide is the "C" in CHOP).  As with all CAR-T, each patient had some T cells (a kind of immune cell) removed. The T cells were changed so they recognized the cancer cells as something they should go after instead of ignoring. Then they put back into the patient so they can do their work.

The Overall Response Rate for the Follicular Lymphoma patients was 94%, with 89% getting a Complete Response. The treatment works a little bit slowly, with a median response rate of over 1 month. After 2 months, some of the patients who had a Partial Response ended up with a Complete Response.

The response rate for these indolent lymphoma patients was even better than it has been for the aggressive lymphoma patients. Dr. Jacobson said the researchers weren't sure why, though they think the conditioning agents (the chemo they got before the CAR-T) might have helped some. 

After 17 months, the median duration of response hadn't been reached yet. In other words, more than half of the patients (64%) were still responding to the treatment -- the cancer hadn't come back yet for them.

As far as safety goes, about 86% of patients in the trial had serious side effects, including drops in blood cell counts, and increased rates of infection (as white blood cell counts drop, the immune system is weakened). One patient in the trial died due to Cytokine Release Syndrome. Still, Dr. Jacobson thinks it is possible to eventually give the treatment on an outpatient basis, meaning the patient wouldn't need to stay in the hospital.

Like all treatments, the side effects can be problematic, though from what I have read, as more patients receive CAR-T, doctors are getting better at anticipating and treating them. 

My guess is that we will see some updated results about this in a few months at the ASCO conference.

As great as CAR-T has been for many patients with aggressive forms of Follicular Lymphoma and other blood cancers, it's exciting to think that a treatment with such a high response rate might be available to more us in the fairly near future. 

One more thing to be hopeful about.

Updated CAR-T Research

The latest issue of the journal Blood has some updated research on CAR-T in Follicular Lymphoma. The article is called "High rate of durable complete remission in follicular lymphoma after CD19 CAR-T cell immunotherapy."

The article describes results f a phase 1/phase 2 clinical trial involving 21 patients with relapsed/refractory Follicular Lymphoma (13 patients) and transformed Follicular Lymphoma (8 patients). This data comes from a larger trial involving CAR-T and a bunch of different blood cancers.

Patients in the trial were first given a chemo combination -- Cyclophosphamide (the C in CHOP) and Fludarabin. This was done for lymphodepletion -- cutting down on the immune cells in the body. Then they were given the CAR-T (immune cells that had been removed from the patients and changed so they would recognize and destroy cancer cells).

The results were strong -- 88% of the R/R FL patients had a complete response, and all of them remained in remission after a median follow-up of 24 months. For the transformed FL patients, 46% had a complete response, which lasted a median of over 10 months. As fr side effects, 50% of the R/R FL patients had both Cytokine Release Syndrome and nerve issues, while 39% of the transformed patients had CRS and 23% had nerve issues.

The link above only provides an abstract, not the full article, but a commentary about the research was also included, and can be seen for free -- "The case for CAR T-cell therapy in follicular lymphomas."

The commentary adds some interesting information. Other trials (like ZUMA-1 and JULIET) have looked at CAR-T in aggressive lymphomas, so it's hard to compare the results of this trial to them. But the splitting out of R/R FL patients and transformed FL patients is very helpful. We can see that CAR-T can be very effective for patients who continue to need treatment, but who haven't transformed to a more aggressive lymphoma like DLBCL.

The commentary also points out the the chemo given for lymphodepletion was not the same for everyone.  Some of the R/R FL patients received more Cyclophosphamidethan others. Perhaps that had an effect, and it's why the R/R numbers were higher than the transformed numbers? Interestingly, the patients in the other CAR-T trials also had differing lymphodepletion amounts. In the JULIET trial, some patients had none at all, and their CR rate was only 29%.

Looking at the title of the commentary, "The case for CAR T-cell therapy in follicular lymphomas," it's easy to see why the author is optimistic. Not every trial results in huge steps forwad, but even s,all steps are important. And maybe something like paying more attention to lymphodepletion strategies will result in a big step.

In the meantime, we can share the author's optimism that CAR-T might seems to have a god and lasting effect for many patients who are R/R, but who aren't transformed. And at some point, maybe we'll see CAR-T available as a first-line treatment as well.

No one is suggesting miracles just yet, but "promise" is a pretty hopeful word.

CAR-T Follow-Up

More good news for CAR-T -- the Zuma-1 trial is reporting good results from the 6 month follow-up of 101 patients with aggressive lymphoma.

Let me make that clear: this news has to do with patients with aggressive lymphomas. I wrote about the 3 month results of the trial in February.  The patients were divided into two cohorts. Cohort 1 was made up of 77 patients with Diffuse Large B Cell Lymphoma. The other 24 were in cohort 2, and included a small number of patients with Transformed Follicular Lymphoma. It's those few transformed FL patients that really caught my eye. They did very well in the first trial.

The numbers are now in for the 6 month follow up. The responses are down some -- patients that had responded immediately and kept their response up for 3 months were very high (for all 101 patients in both cohorts, there was an 82% Overall Response, and 54% Complete Response). After 6 months, the numbers are 41% OR and 36% CR. Still very good, though not as eye-popping as the first results.

For patients in cohort 2, which included the transformed FL patients, the results were even better than the whole group: at 3 months, 83% Overall Response and 71% Complete Response. After 6 months, they also dropped, but not as much: 54% OR and 50% CR.

Unfortunately, the 6 month update does not include separate numbers for the transformed Follicular Lymphoma patients. And it was a pretty small number of FL patients to begin with (just 6).

Still, those are darn good numbers. As someone who (like many of you) always has transformation in the back of mind, I like to hear about a treatment that helped half the people who took it.

All of thee patients, by the way, are chemorefractory -- that is, they had chemotherapy, but it didn't work. It would be great to have another back-up for CHOP.

The other piece of good news from this is that side-effects seemed to be about the same after 6 months as they were after 3 months. There were still some significant side effects (many related to lowered blood counts of different types), though they seemed manageable. And a few side efefcts went down, including patients with Cytokine Release Syndrome (CRS), which fell from 18% to 13%. (That's probably the most serious of the side effects, and comes when the body is overwhelmed with trying to clean up all of the cancer cells that the CAR-T is killing off so quickly.)

The full results will be presented in April at the American Association for Cancer Research conference. The company that makes this CAR-T treatment is planning to use these results to start seeking regulatory approval for the treatment. That could be good news for all of us.

I'll keep on keeping an eye out for more promising CAR-T news.

CAR-T for NHL

OncLive has an excellent video series on CAR-T. They usually spread their video series over a couple of weeks, with a new installment every few days.

Today's installment is called "Expanding the Role of CAR T in Non-Hodgkin Lymphoma," and it features comments from Dr. Nilanjan Ghosh of the Levin Cancer Institute in North Carolina; Dr. Leo Gordon from Northwestern Memorial Hospital in Chicago; and Dr. Matthew Lunning from the University of Nebraska Medical Center.

This video is fourth in the series. The others cover some basic information about how CAR-T works, and some practical issues like cost. It's a good introduction to CAR-T. (And, of course, if you want to learn more, especially from a patient's perspective, you might consider checking out the CAR-T and Follicualr Non-Hodgkin's Lymphoma blog, run by some folks with first-hand experience as patient and caregiver.)


I found this video on expanding the role of CAR-T especially interesting. In one of the online groups I am in, someone complained this week about not being eligible for CAR-T because her disease wasn't aggressive enough. Lots of grumbling followed. People seemed to think that the treatment was being kept from them unfairly.

That is not the case. A couple of versions of CAR-T have been approved by the FDA, but approval, of course, is always for very specific situations. And for Follicular Lymphoma, that means patients with a particularly aggressive form, who have already tried a certain number of treatments.

There are trials that are looking to expand who can get CAR-T, but it's going to be a little bit of time before we know how well it works for those folks.

This particular video gets into some of the issues that surround making CAR-T available to me people. There are a couple of trials looking at CAR-T after the patient has had a transplant. There are questions about whether CAR-T could work for someone with MRD -- Minimal Residual Disease (in other words, how many cancer cells need to be around for the CAR-T to attack in order for it to work?).  Is it better to use this on POD24 patients (those who have the disease come back with 24 months after they have had chemoimmunotherapy)?

Lots of questions about CAR-T, and only time will give us the answers.

My new oncologist, Dr. H, thinks CAR-T will be much more effective in 5 years. We'll have more data from more trials, and we'll get a better sense of just who this treatment will work for. We've had lots of success stories so far (and a few failures). Maybe in 5 years we look forward to more of thsoe successes.

Click above for the video. If the link doesn't work (or if you need a transcript for translation), OncLive provided a very helpful transcript, which I am including below:




Nilanjan Ghosh, MD, PhD: One of the future directions for CAR T-cell therapy in relapsed/refractory B-cell lymphoma is to see if it can be moved up from second-line, and after failure of second-line to an earlier line. It has good activity in most patients, so this is a natural evolution. The question is, can it be compared to transplantation? There are 3 clinical trials that have been planned for this possibility. There’s ZUMA-1, in which axicabtagene ciloleucel [axi-cel] is being compared to salvage therapy followed by transplantation. There’s a trial called BELINDA in which CTL019 [Kymriah] is being compared to salvage therapy followed by transplantation. All these trials are going to see whether patients who are failing first-line therapy, have relapse, and thereafter can receive CAR T-cell products compared to other salvage therapies.

Leo Gordon, MD: The timing of CAR T therapy is an evolution. Currently, it’s for patients with refractory disease, but perhaps consolidation for patients with responding lymphoma who are high risk for relapse would be a good fit. Should it be used as consolidation for patients in complete remission? This begs the question: Do you need antigen in order for this to work? In other words, do you need some tumor present in order for CAR T-cell therapy to work? Will it work with minimal residual disease with no obvious antigens that are there for the CARs to attach to? We do not know the answer.

At the moment all the patients treated have had visible disease on PET [positron emission tomography] scans and physical exams. Whether it works in patients with no obvious disease, we don’t know. Saying it might be used as a consolidation treatment would probably be premature.

As we try and advance the use of these, ultimately the CAR T therapies themselves are going to be better; there are going to be better costimulatory molecules. There’ll be more educated cells that might be targeting a variety of different targets on tumor cells. Additionally, we’re exploring the so-called Platform study, which is being done with Celgene-Juno with the same JCAR017 molecule cell product. We’re looking at the use of adding certain agents to CARs, such as PD-L1 [programmed death-ligand 1] checkpoint inhibitors.

We’re looking at immunomodulatory imide drugs [IMiDs], a variety of other drugs that we think might enhance the efficacy of these CARs, perhaps by reducing the number of T-regulatory cells, which might get in the way of the CARs working. In the future, there are going to be better CARS and costimulatory molecules, and there will be perhaps the use of combinations of treatment—maybe radiation, which will help release antigens and make the CARs more effective radiations to certain sites of disease.

Matthew Lunning, DO: Clinical trials are ongoing in follicular lymphoma, mantle cell lymphoma, and chronic lymphomatic leukemia [CLL] looking at CAR T cells in these spaces. If you take each one of those diseases—it’s a spectrum—it’s just like large B-cell lymphoma. Patients with follicular lymphoma receive an anthracycline-containing bendamustine [Bendeka] regimen, which in the refractory setting is a front-line therapy that becomes more intensive in the second-line setting as the lymphoma progresses. This is an acceptable patient for CAR T-cell therapy, I think, on a clinical trial.

One could argue that a patient who relapses within 2 years from front-line anthracycline-based chemotherapy is a big deal. Fifty percent of those people are not alive in 5 years, and their likely cause of death is lymphoma. That’s a population in follicular lymphoma that I would want to study with CAR T cells. Mantle-cell lymphoma is another population I would like to study. It can definitely behave like the most aggressive lymphomas in the relapsed/refractory setting.

You have to be able to discern which one of these it is behaving like. The same thing goes for CLL. In mantle cell lymphoma, again, if you’ve gotten front-line chemotherapy and consolidated with an autotransplant, and you relapsed quickly after an autotransplant, that might be an area where CAR T-cell treatment would be a reasonable strategy. Some may argue that that patient should at least get a trial of ibrutinib [Imbruvica] tyrosine kinase inhibitor prior to going to CAR T cell.

The answer, if you look at the efficacy that’s been displayed across the 3 constructs, is that if it’s going to work, if it’s agnostic to double-hit or triple-hit refractory in 6 months, or after autotransplant, you can still see responses with durability in that patient population. Even in indolent lymphomas where you’re talking about that tough population, there may be the opportunity for efficacy, but you have to be mindful of the potential toxicity. It’s always a risk-benefit discussion with the patient and family regarding CAR T-cell therapy

ASCO: CAR-T

First of all, a Happy Cancer Survivor's day to everyone!  The National Cancer Survivors day Foundation defines a survivor as anyone who has been diagnosed with cancer who is still alive today. It's a day worth celebrating. In fact, it's a reminder that every day is worth celebrating -- we should be sure to take some time, every now and then, to remember that.

I'm not going to spend too much time on Cancer Survivor's Day today (if you want to look back at what I had to say in the past, feel free -- it still holds true, especially the part about having a crush n figure skater Katarina Witt when I was a teenager).

More importantly, there are ASCO abstracts still waiting out there to be discussed.

My friend William asked me to check out what's being said about CAR-T. (William and Ben write a blog on CAR-T and Follicular Lymphoma. Ben had CAR-T, as did William's wife.)

There is a LOT of stuff on CAR-T at ASCO. It's an exciting treatment that shows a lot of promise. I've written about it before (a lot), but here's a reminder of how it works:

One of the body's defenses against invaders is a kind of white blood call called T cells. There are actually a bunch of different kinds of T cells, but there basic job is to figure out that there is an invader (like a bacteria or a virus) and attack it. T cells can multiply rapidly, so millions of them go on the attack.

But T cells don't work on cancer cells. Cancer isn't an invader from outside -- it's our own cells that have gone wrong. So CAR-T is a way of using T cells to go after cancer cells. Some T cells are removed from the body and changed in a way that lets them treat cancer cells as outside invaders. The new T cells can multiply and overwhelm the cancer just like they would any invader.

CAR-T is still in developmental stages (though it has been approved for aggressive transformed Follicular Lymphoma). Right now, about one third of patients have a long response to CAR-T, about one third have a response that lasts less than a year, and about one third do not have a response. My own oncologist thinks it will be much more effective in about 5 years. Another problem is that it is expensive -- it is basically a personalized cancer treatment, made just for each specific patient. It can also have some serious side effects, as the body is overwhelmed by the army of T cells, causing a reaction that could be fatal if not treated.

With so many presentations on CAR-T at ASCO, I won't get into too much detail about them, but here are some of the highlights:

• One studied looked at Quality of Life in CAR-T versus Stem Cell Transplants. Unfortunately, aggressive treatments can result in severe side effects and lower QoL. The study found that CAR-T patients had the same QofL as the STC patients, and may have had fewer physical side effects in the month that followed treatment/
• Another looked at Cytokine release syndrome, also known as CRS. That's the potentially deadly reaction that the body has when so many T cells kill off other cells at one time. the body has a reaction that's almost like getting a really bad flu. One presentation offered a way to detect CRS and deal with it before it becomes too harmful. (This has been a big area of research for the last few years, and it seems like doctors are able to watch for CRS and deal with it early.)
• Another used PET scans as away to predict how effective a CAR-T treatment would be. By looking at a PET 30 days after CAR-T treatment, and comparing it to PETs taken after 90 days, researchers could figure out how to tell if the 30 day PETs could predict whether or not the CAR-T would be successful. early predictors like this are important; rather than waiting another 2 months to see if it worked, some patients can start a new treatment much sooner, saving valuable time.
• Another looked at outcomes for DLBCL patients who had CAR-T. they found that patients who relapsed within 3 months of treatment had poor outcomes. But those who relapsed 3 months or longer after getting CAR-T did much better with the treatment that followed.

There weren't any presentations that looked at only Follicular Lymphoma and CAR-T. The clinical trial series that focuses on CAR-T and lymphoma is called ZUMA. So ZUMA-1 looked at DLBCL and Transformed FL, and the results of that trial were the reason CAR-T was approved. There are a bunch of trials (at least 8) that are looking at CAR-T and other blood cancers. One of them is looking at FL (not transformed FL, but just regular old FL). No results yet, at least not anything worth presenting at ASCO. Maybe at ASH in December, or ASCO next year.

I'm looking forward to seeing how CAR-T improves over the next few years. There is certainly a lot of research that's looking into making it happen.

ASH: Natural Killers and Follicular Lymphoma

One more from ASH.

But first, Targeted Oncology wrote up a recap of ASH a couple of days ago, and described the presentations that they thought were most significant.  They list a few under Lymphoma, and the ones that focus on Follicular Lymphoma are those that focus on CAR-T (the ZUMA-5 trial) and on Bispecifics (there are a few of them). I mention this because those are the the ones that I saw the most buzz about online during and after ASH. So it's nice to see that the things I heard are also the things other people heard. I like being right. (And it should probably be comforting to you to know I get things right.)

Now, back to the last "buzzy" presentation at ASH that looked at Follicular Lymphoma:

 "Results of a Phase 1 Trial of Gda-201, Nicotinamide-Expanded Allogeneic Natural Killer (NK) Cells in Patients with Refractory Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma."

GDA-201 is a treatment that involves Natural Killer Cells. These are a type of immune cell found in our bodies. Unlike some other immune cells that attack an invader (like a bacteria or virus), Natural Killer Cells attack our own cells that have been infected with an invader. Viruses, for example, work by taking over a cell and then multiplying rapidly. A Natural Killer Cell recognizes that this infected cell is different from other normal, and kills it off.  

This makes a Natural Killer Cell a really interesting target for Immunotherapy. Our own immune systems don't kill off cancer cells because cancer cells are not "invaders" or outsiders. Instead, cancer cells are our own cells that haven't learned how to die the way they are supposed to. Most of our immune cells will look at our own cells and leave them alone. But a Natural Killer Cell is made to say, "Hmm, something's not right here." But even a Natural Killer Cell won't kill off a cancer cell. Still not different enough from regular cells to be concerned.

GDA-201 gets around that by using someone else's Natural Killer Cells. The donor cells are trained to recognize cancer cells (the way the NK cell would recognize a cell that had been taken over by a virus), and goes after them. GDA-201 isn't the only attempt out there to use Natural Killer Cells, but it's the one that, so far, has shown some success with blood cancer.

For this research, donor NK cells were manipulated and grown in a lab. The cancer patients in the study were then given a monoclonal antibody (like Rituxan) to kill off or weaken a lot of the cancer cells. Then the NK cells were put into the patient.

Results were very good. It's a phase 1 trial, so there weren't many patients -- 15 with lymphoma and 15 with multiple myeloma (another blood cancer). Of the lymphoma patients, 6 had Follicular Lymphoma.

The good news is, all 6 FL patients had a Complete Response. For the whole Lymphoma group, the median duration of response was almost 9 months.  One-year estimates of Progression-Free Survival was 66%, and Overall Survival was 82%. 

Side effects were manageable. There was some concern that something like Cytokine Release Syndrome, which is common in CAR-T and some other immunotherapies, might be an issue. But at least at the doses that they tested, there were not any unexpected side effects (though there were some, of course).

This is a phase 1 trial, with very few participants, so there's certainly no guarantee that those good results for FL patients will remain in later trials. But it does seem like the makers of GDA-201 are planning to move ahead, and we'll likely see more of this treatment in the future. I kind of have a good feeling about this. (And hey, I was right about the other stuff, wasn't I?) 

But seriously, the concept does make sense, and I do think we'll hear more about this one n the next few years.

So no big blockbusters at ASH this year, but a few small things that are worth being excited about. At this point, we know that even small progress is still good progress.