Bispecifics for Follicular Lymphoma

I've mentioned bispecifics in my last two posts, so I thought I'd look into them a little more.

BioPharmaDive published a nice piece last week called "At ASH, Bispecific Cancer Therapies Make a Mark." It does a nice job of explaining what bispecifics are and why they made a mark at ASH.

Maybe the easiest way to understand a bispecific is to compare it to a monoclonal antibody like Rituxan. Rituxan (as you may know) works by looking for a protein on the cancerous B cell called CD20 and attaching itself to it. From there, it can kill off the cell in a few different ways. (Watch this cool animation video to see cancer cells die.)

The important thing here is that the one side of the Rituxan attaches the the cell.

A bispecific works in a similar way, but instead of attaching with one side, it attaches to two -- the the cancer cell on one end (like Rituxan), but to an immune cell on the other. Like Rituxan, one end attaches to the CD20 protein, while the other end attaches to a CD3 protein on the immune cell. In this way, the bispecific brings the two cells together -- the cancer cell and the immune cell that is meant to kill it off.

There were three bispecifics discussed at ASH that target B cell lymphomas. All of them target CD20 on on end and CD3 on the other.

The first is Mosunetuzumab. In its phase 1 trial, 98 patients were enrolled. 55 of them had DLBCL or transformed Follicular Lymphoma, and 29 more had regular old FL. There was a 41% Response Rate (33% for the DLBCL/transformed group, but 61% for the FL group), with 27% having a Complete Response (21% of the Diffuse/transformed group and 50% of the FL group). Side efefcts were tolerable. The responses even came for patients who culd no longer take Rituxan, or who tried CAR-T but did not have success. The median follow-up for the study was a little over a year.


The second one is called REGN1979. It was also tested in a phase 1 trial, with 54 patients (16 of them had FL). A number of patients had to withdraw from the study because it didn't work, and their disease got worse. Phaee 1 trials focus on side effects (again, they were called manageable) and figuring out what the best dose would be. For patients who had a particular dose (more than 5mg), there was a 100% response rate for FL patients (5 Complete and 2 Partial Responses).

The third is RG6026.  Again, patients were in a phase 1 clinical trial -- 64 with aggressive B cell lymphomas, including transformed FL, and 17 with FL. Again, at a certain dose (300 µg or above), 3 of 5 FL patients had a Response, with 2 of them having a CR. Side effects were manageable.

One of the issues that is discussed in the abstracts is Cytokine Release Syndrome. This is also a problem with CAR-T treatments. When the body has so much T cell activity, the patient can develop flu-like symptoms, and they can be life-threatening. Researchers were aware of this possibility and took steps to deal with it.

The important thing to remember with these, of course, is that they are all phase 1 studies, and they haven't involved a lot of patients. Larger phase 2 studies will be necessary to figure out if they are as effective as they seem, and then even larger phase 3 studies will really let us know.

(Dr. H, my new oncologist, told me that this kind of treatment might be one that I would want to consider. My new hospital is part of the clinical trial for one of the three treatments.)

Interestingly, according to the BioPharmaDive article, one of the people involved in one of the trials thinks the bispecifics might work even better as part of a combination (which is, of course, the direction that lots of new treatments are going in).

However, another person looking at the results was a lot less impressed after looking at the numbers.

Time will tell. Perhaps one or more of them will move on to a phase 2 trial, and we will see how things go.

For now, though, I'll take my new oncologist's excitement about them as a a good sign, and hope for the best.