ASH Review: Odronextamab (Bispecific)

 First of all, a couple of photos from the ASH conference (I wasn't there, but there are a whole lot of photos from the conference on Twitter):

 

The first photo is a group of oncologist/hematologists (I blocked out their faces). The second one are the ASH mascots: a white blood cell, a drop of blood, and (I think) a macrophage, another type of immune cell. The blood mascot made an appearance last year, I think, but the other two are new. I'm glad everyone had a good time (that's what conferences are for, in addition to learning about new research). But if I was a platelet, I'd be pretty unhappy that I was left out.

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One the bad things about not being able to go to a conference like ASH in person is that I miss out on things like photo ops and mascots. But ASH happens at the worst time of year for me for my job, and they don't offer discounted registration for independent patient advocates anyway. 

But the other bad thing is that I only get to read the abstracts -- the summaries of the presentations that I always link to. Those presentations are usually presented as posters (with a little more detail than the abstract) or oral presentations (with a lot more detail, plus questions from the audience). For the presentations that seem to make the most impact, there will at least be some discussion on Twitter, or maybe a press release from the researchers, and some discussion online immediately afterwards. 

Today is the last day of ASH, so I'm starting to see some of those press releases and online discussions. And it's clear that bispecifics are the big news for Follicular Lymphoma this year. People seem very pleased with the updated results for Mosunetuzumab, as I discussed in my last post.

But more controversial are the results for Odronextamab, a different bispecific (I gave this a very brief mention in my last post, because the results seemed good, but not overly exciting to me, based on just the abstract.

However, there are two stories being told about Odronextamab today, after the ASH presentation last night. One is very positive, and the other is a lot more cautious. 

The official story from the company that makes Odronextamab is the very positive one, as their press release makes clear. And the results do show some very good effectiveness. Odronextamab is a CD20 x CD3 bispecific -- it attached to the CD20 protein on a lymphoma cell, and then to the CD3 protein on a T cell, an immune cell that can kill the cancer cell. The results from the phase 2 clinical trial show that it had an 82% Overall Response Rate for patients with Relapsed or Refractory Follicular Lymphoma, with a 75% Complete Response Rate. Those are excellent numbers for a phase 2 trial. The company says they are the highest response rates ever for R/R FL patients, and that the trial has set a "new benchmark." And the response was durable, with the Complete Response lasting a median of 20.5 months.

But then there's the other story, which focuses on safety. As several commenters have pointed out, there are some very serious side effects with this trial. In fact, Odronextamab was put on clinical hold two years ago because of serious side effects.

One of the big side effects was Cytokine Release Syndrome (CRS), which seems common in bispecifics, and definitely in CAR-T. And there were others --- all 131 FL patients had side effects, with 118 of them related to the treatment. There were 81 serious events. There were also 17 deaths recorded during the study, with 6 of them related to the treatment (the others were for things like Covid), with causes such as pneumonia, a brain infection and a fungal infection. Another 15 patients had to leave the trial because of problems like CRS, tremor, epilepsy, high liver enzyme s, etc. The company points out that it did take steps during the trial to cut down on some of these side effects like CRS.

 

The company that makes Odronextamab is planning a phase 3 trial immediately, but is also going to apply to the FDA for accelerated approval. It has already been given Orphan Drug Designation was for FL by the European Medicines Agency (which means it will get some special help during the approval process). It will be very interesting to see what regulators have to say about the side effects. As one lymphoma expert pointed out on Twitter, Mosunetuzumab doesn't seem to have these same safety issues, despite using a similar mechanism.

So far, this has been the most-talked-about presentation from ASH this year. It officially ends today, so there will probably be more experts weighing in the days and weeks to come.

I think the big lesson here is a reminder that, for now, cancer treatments are always about the balance between effectiveness and safety. Treatments that are very good at killing cancer cells are also more likely to cause problems. It's pretty hard to avoid. Maybe someone will figure out how to do that in the future, but for now, it's about recognizing them early and managing them well. 

I'll continue to look out for expert commentary from ASH, and share what I find out. 

In the meantime, may your days be filled with large, cuddly pathogen-killing immune cells like the ones in the pictures.