ASH: Mosunetuzumb (Bispecific Antibody)

Back to ASH (though, since the conference is over now, I guess this is an ASH review instead of an ASH preview).

If there was anything close to a "blockbuster" for Follicular Lymphoma at ASH this year, it was a session on Mosunetuzumab. All of the presentations I have been writing about take different forms, and there are kind of ways to tell how important the ASH community thinks they might be. One sign is how big the room is where the information is presented. If they expect a lot of people will be coming to hear about it, they'll put it in a big room.

The Mosunetuzumab presentation was in a big room.

 (And thanks to the anonymous reader who commented about this. You were a couple of days ahead of the cancer news sites.)

Mosunetuzumab has been on my radar for just about a year. It created some excitement at last year's ASH conference, and when I had my first appointment with my newest oncologist, he mentioned it as something we might consider if and when I need treatment again. The hospital I go to for appointments is participating in the clinical trial for Mosunetuzumab.

If you pay attention to treatment names, you now that Mosunetuzumab is a Monoclonal Antibody, or a MAB, which is why the name ends in -mab. Rituxan is a MAB, too -- I usually use that name, but its non-branded name is Rituximab, and in some parts of the world, it's known as MabThera.

What makes Mosunetuzumab different from a MAB like Rituxan is that it is "bispecific." Rituxan works by targeting a protein called CD20, which is on the surface of the cancer cell. When it comes across a cell with CD20, it attaches itself and works to kill it off. Mosunetuzumab also finds cells with CD20 and attaches itself. But it also finds immune cells with a protein called CD3 and attaches itself to them. "Bi" means "two." A "bispecific" MAB attaches itself to two cells -- one that it hopes to kill off, and one (an immune cell) that can help it do the killing.

So you can see why, in theory, it could be an effective treatment.

"Theory" is nice, but what about in reality?

 Well, there was a reason it was in a big room.

The session was called "Mosunetuzumab Induces Complete Remissions in Poor Prognosis Non-Hodgkin Lymphoma Patients, Including Those Who Are Resistant to or Relapsing After Chimeric Antigen Receptor T-Cell (CAR-T) Therapies, and Is Active in Treatment through Multiple Lines."

 The title kind of gives the highlights, but here are some of the details.

The study is a phase 1 trial, so in addition to measuring how effective Mosunetuzumab is, the study also looked at safety, and at dose escalation (figuring out how much to give to be most effective and most safe).  There were 218 patients in the study, and 69 of them had Follicular Lymphoma. Another 29 has transformed FL. 16 patients had already received CAR-T (4 with FL, 5 with transformed FL).

The results were very positive. For patients with indolent lymphoma (including FL), the Overall Response rate was 64.1%, and the Complete Response rate was 42.2%. For patients who had already had CAR-T, the ORR was 38.9% and CRR was 22.2%. (That's important, since about 2/3 of CAR-T patients relapse, and the need for a follow-up treatment is great for them.)

After 6 months, the patients who has received a CR were still mostly doing well -- 83% of patients with indolent lymphoma still had a CR, as did 71% of patients with aggressive lymphoma.

Also, 4 patients who had stopped responding to Mosunetuzumab had a response when they were treated a second time, with one of them having a CR.

Based on the number of news stories I have seen in the last few days, there is a lot of excitement in the lymphoma community about Mosunetuzumab's potential. Like all immunotherapy, it uses the body's immune system to fight cancer cells (which can usually escape the immune system). CAR-T is a very effective immunotherapy, but takes time and a lot of money to develop, since it is made specifically for each individual patient. Mosunetuzumab is an "off the shelf" treatment (a phrase that lots of experts have used -- it doesn't need to be specially made for each patient).

How effective will Mosunetuzumab be? We'll have to wait to find out. Long-term results will take time to figure out, and the dose escalation (how much to give to be most effective) is still being worked out. This is a phase 1 trial, after all.

It all reminds me a little bit of R-Squared. Lots of early excitement. Let's hope the same results comes about -- an alternative to chemo that is safe and effective and gives us another option.