Concerns about Bispecifics

OK, that didn't last long.

I'm not talking about the whole "2021 is going to be so much better than 2020!" (and that's all I'll say about that).

Clinical trials for Odronextamab have been paused for safety reasons.

Odrenextamab is a bispecific that I wrote about just a few weeks ago. Here's what I said:

"Bispecifics have the potential to be even greater than monoclonal antibodies like Rituxan (also known as MabThera) or Obinutuzumab (also known as Gazyva). Lymphoma experts are excited about that potential, and they had lots to say about some of the presentations at ASH. The first was Odronextamab, which has been going by the name REGN1979. I wrote about this last year. REGN1979 is one of those bispecifics that attaches to the cancer cell (through CD20) and to an immune cell (through the protein CD3). The ASH presentation that is getting people excited is called "Odronextamab (REGN1979), a Human CD20 x CD3 Bispecific Antibody, Induces Durable, Complete Responses in Patients with Highly Refractory B-Cell Non-Hodgkin Lymphoma, Including Patients Refractory to CAR T Therapy." 

I won't give any more background about bispecifics (you can go to the link on your own). But here's the problem (which was announced a couple of weeks after the ASH presentation) -- some patients are having issues with Cytokine Release Syndrome (CRS), a potentially deadly side effect. 

CRS can occur with some immunotherapy treatments (it's fairly common in CAR-T). When the immune system has a sudden rush of white blood cells attacking an invader (or a cancer cell that they have been told is an invader), the cells can send out signals (cytokines) that cause more white blood cells to be released. White blood cells are usually good things, since they fight off invaders. But too many, especially all at once, can cause many problems. Some of them are mild, and some are very serious. Enough patients in the Odronextamab trial had more serious versions of CRS that they put a pause on it.

The company developing and testing the bispecific is pausing the trial, not cancelling it, meaning they are not enrolling any new patients. The FDA has requested that trial protocols (basically, the procedures that need to be followed) be changed to account for the CRS.

The important thing to remember is that CRS, while serious, is also fairly common. One of the problems with early CAR-T trials was CRS, in some cases very serious CRS, resulting in death. (Technically, it was a Cytokine Storm, which happens immediately after a treatment, while CRS is usually what they call a similar reaction that happens over time). Researchers made it a priority to look for signs of CRS so they could be dealt with immediately. 

Just my guess (and this is a good time to remind you that I'm not a doctor or a cancer researcher, just someone who reads a lot) -- the trial will be paused for a while but will probably go on with some changes to manage patient safety. 

It's a also a good time to remind you that all treatments have safety issues -- nothing is without side effects. That's why clinical trials exist. They help determine how effective a treatment is, but also how safe it is, and approval only happens when the side effects are determined to be worth the cost, given the effectiveness. I know I sometimes get caught up in the numbers, and focus on things like Response Rates. I have to remind myself to pay attention to safety, and to make sure I'm making that clear to you, too.

We're getting into a little bit of a doldrums period now, where there isn't as much research news to share for a month or so. But I'll keep looking. 

On the other hand, there's a special day coming up soon, so keep an eye out for that....