Anti-CD47 Treatment for FL

The New England Journal of Medicine just published the article "CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin’s Lymphoma." It describes research that people are very excited about, and that could provide a new path for treating Follicular Lymphoma.

Some background first. The article describes a type of immunotherapy. There are lots of immunotherapy treatments out there already and in development, but they all involve getting the immune system to attack cancer cells. The immune system's job is to defend against outside invaders (like bacteria and viruses). That doesn't help against cancer cells. They aren't outsiders -- they are parts of our body that went from normal to abnormal. 

Immunotherapy treatments work in one of two general ways -- either change the cancer cells to make them look like outsiders that the immune system knows to attack, or change immune cells to recognize the cancer cells as something that should be attacked and defended against.

For a treatment like CAR-T, the immune cells are changed.

In the treatment described in this article, it's the cancer cells that are changed.

The article describes a treatment called Hu5F9-G4. (You can tell this is a really early trial because the treatment doesn't have a cool name with a Z or an X in it yet.)

Hu5F9-G4 works by targeting the protein CD47, which sits on the surface of some cancer cells. CD47 is important because, as the descriptions of the research say, it gives a "don't eat me" signal to immune cells. But Hu5F9-G4 blocks that signal, so the cancer cells are vulnerable. When that happens, an immune cell called a macrophage can recognize it as an invader. The word "macrophage" comes from the Greek words "makros" and "phagein," which together mean "Big Eater." Macrophages eat the invaders.

[How did I do there, Ioannis? Is my Greek pretty good?]

This treatment also included Rituxan, which targets a different protein, CD20. So between the two agents, you have twice the chances of getting to the cancer cells.

Now, the article describes results from a phase 1b/2 clinical trial. A phase 1 trial will basically figure out how much of a treatment to give, and the phase 2 trial will give the treatment to a particular group that might benefit from it. Both phases usually involve a pretty small group of patients. 

For this trial, there were just 22 patients, 15 with Diffuse Large B Cell Lymphoma, and 7 with Follicular Lymphoma. All of them were heavily pre-treated -- they had tried at least 2 other treatments, and as many as 10 treatments. And almost all of them were refractory to Rituxan (meaning it had stopped working).

And the results were good. 50% of patients had a response, with 36% of them having a Complete Response. The FL results were especially good, with 71% Overall Response and 43% Complete Response. After 8 months, 91% of the responses were still holding.

People are excited about this for a couple of reasons. First, getting macrophages involved is new -- it's a different type of immune cell that might be used to attack cancer. Second, it seems to work for some patients who aren't able to use Rituxan anymore. 

But there are certainly some questions, too. It's a very small trial, as phases 1 and 2 trials tend to be. The treatment needs to be tested on a larger group of patients before we can get ourselves too excited.

But if nothing else, this is another path for researchers to follow. There are a bunch of anti-CD47 presentations at ASH this year, for lots of different blood cancer. That's promising.

Certainly another one to keep an eye on. 

(And more on ASH coming soon.)