ASH: Bispecifics for Follicular Lymphoma

More on ASH.

As I said in my last post, now that the ASH conference is over, and companies and researchers have made their presentations and seen the reaction to them, there has been more discussion online about them. I've been seeing a lot of discussion about three things related to Follicular Lymphoma. The first one (which I discussed last time) is the ZUMA-5 trial, which looked at CAR-T for slow-growing, indolent lymphomas like FL. 

The second one is the excitement about bispecifics. A bispecific is a treatment that attaches to two proteins instead of one (which is where the "bi" comes from).

Think of it this way: a treatment like Rituxan is a monoclonal antibody. It works by seeking out a specific protein on blood cancer cells, called CD20. When the Rituxan finds a B lymphocyte (the white blood cell that turns cancerous for us, and which has CD20 on the surface), it attaches to it and kills it. I haven't linked to this in a while, but here's a cool video that shows how Rituxan kills cancer cells. 

I bispecific works in a very similar way, but instead of attaching to one protein, it attaches to two of them. Since we're looking at cool videos today, here's one from Genentech that describes how bispecifics work. Because bispecifics are created antibodies, they can be manipulated to go after cancer in a bunch of ways. For instance, they can attach to two different proteins on the surface of a cancer cell, doubling the chances of the treatment finding the cancer. Or they can find and attach to two different cells -- one cancer cell, and one immune cell, so the immune cell can more easily get to the cancer cell. 

If you've been reading the blog for a while (or if you're just a cancer nerd), you know that Rituxan has played a big role in the jump in Overall Survival for Follicular Lymphoma in the last 20 years or so. Rituxan can do a great job on its own for some people (like me), but really shines when it is combined with other treatments, whether traditional chemotherapy (think R-CHOP or B-R) or non-chemo (think R-squared). But 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." 

In this study, 127 patients with Relapsed or Refractory B cell Lymphomas (including 37 with Follicular Lymphoma) were given Odronextamab. The FL patients did well. This was a dose-escalation study, which meant they tried different doses to see which was most effective. For FL patients who received a particular dose, the Overall Response Rate was 93%, and the Complete Response Rate was 75%. The median duration of response was 7.7 months, and the median duration of Complete Response was 8.1 months. Pretty good.

What really got researchers excited, though, was in some of the patients with Diffuse Large B Cell Lymphoma, a more aggressive lymphoma than FL. In particular, there were some patients who had CAR-T, but whose cancer returned. For those patients, the ORR was 33%, and the CRR was 23.8%, with all 5 of the CRR patients still having a response. That's pretty cool, and should provide some hope to that population, especially if researchers find ways to improve on that number. 

Another bispecific that got some attention was Mosunetuzumab.  This bispecific has been getting some buzz for three years in a row now. The presentation is called "Mosunetuzumab Shows Promising Efficacy in Patients with Multiply Relapsed Follicular Lymphoma: Updated Clinical Experience from a Phase I Dose-Escalation Trial." 

Like Odronextamab, Mosunetuzumab is a CD20/CD3 bispecific, attaching to a cancer cell and to an immune cell. This study focuses only on FL patients (62 of them), though all were relapsed or refractory. Numbers were good here, too. The Overall Response Rate was 68%, with a 50% Complete Response Rate. CRR was good for high-risk patients, including POD24 (53%) and the 4 who received CAR-T (50%). The median duration of response was a little over 20 months.

Of course, all treatments come with side effects, and bispecifics are no different. They included many of the side effects that come with blood cancer treatments, including nerve issues and blood count issues. See the links for more information.

I think this all looks promising. I've been especially interested in bispecifics because my oncologist mentioned them as a possible treatment, if and when I need treatment again. (There was a bispecific trial happening at the hospital I go to.) I don't particularly want treatment, but I really like the idea of bispecifics, and the excitement they are generating. 

One complaint -- Follicular Lymphoma treatments roll out pretty regularly, but not so regularly that I can't learn their names.  But these two seem harder than most. I won't complain if they eventually get approved in a few years, but I'm warning you now to look out for spelling errors.

A little more ASH news to talk about. Come back soon.