ASCO: Bispecifics in the Real World

Another ASCO review. This one is for the presentation called "Real-world outcomes of bispecific antibodies in relapsed/refractory (R/R) follicular lymphoma (FL)."

A little background first. Bispecific antibodies are one of the two general types of treatments for FL that (in my opinion) Lymphma specialists are most excited about in the last few years, with the other being CAR-T. My own oncologist brings up bispecifics as a possiblity if I need treatment again.

Bispecifics work similarly to monoclonal antibodies like Rituxan or Obinutuzumab. Those treatments are able to seek out specific cancer cells by finding a protein on the surface of the cancer cell (CD20) and then destroying the cell. Most of us who have treatment have probably been given one or the other of those monoclonal antibodies. A bispecific also finds and attaches itself to a protein on the surface of an FL cell. But it has another side to it -- one that attaches itself to a T cell, an immune cell. This brings the T cell next to the cancer cell, and the T cell is able to eliminate the cancer cell.

Mosunetuzumab and Epcoritamab are currently the two bispecifics that are approved in the U.S. (and elsewhere). In this presentation, the researchers are interested in how well they work in the real world.

That phrase "real world" means something very specific in cancer research. It refers to how a treatment works after it has gone through clinical trials and been approved. Clinical trials are very limited in many ways. They are designed to put as much focus on the treatment being tested as possible. So clinical trials participants are limited in different ways, maybe by the number or types of treatments they have already received, or by comorbidities -- pre-existing health problems. If the trial designers are concerned that a treatment might cause kidney problems, for example, they won't let anyone with kidney disease into the trial, so if participants develop kidney problems, they know it was the treatment that probably did it.

"Real world" research doesn't have those restrictions. If a clinical trial uses an "ideal patient," a real world study includes everyone, even those who aren't ideal. A great treatment isn't so great if only a limited number of patients can actually use it.

This is a retroactive study, meaning the researchers didn't ask patients to use bispecifics. Instead, they looked back at records of patients who did use them to see how safe and effective they were, especially compared to the clinical trials. A total of 99 patients with Relapsed/Refractory FL were studies. 92 of them had received Mosunetuzumab and 8 received Epcoritamab (Mosunetuzumabhas been available longer). It was a diverse group by age (raging from 33 to 101 years old) and treatment history (ranging from 1 to 14 prior treatments), including 15 who had received CAR-T.

The results were very positive. They were able to collect data from 96 patients. The Overall Response Rate to a bispecific was 87%, including a Complete Response Rate of 72%.  The responses were not significantly associated with other factors like which bispecific they received, their FLIPI score, or whether or not they had received CAR-T. All of them were successful.

The Progression Free Survival rate at 12 months was 72%, and at 18 months was 56%. Overall Survival rate were 94% and 92%. PFS was not influenced by those factors like FLIPI score or CAR-T use. 

As for safety, 34% of patients had CRS (Cytokine Release Syndrome), though none were grade 3 or higher, which is the most serious levels. Only 3% of patients had ICANS (Immune Effector Cell-Associated Neurotoxicity Syndrome). Again, side effects were not assocaited with the other factors mentioned above. 

I'm leaving out some details, which you can see yourself in the abstract. But the conclusion remains the same. This retrospective study included a diverse group of patients who had received lots of previous treatments, and the two bispecifics were effective and safe for most of them, including patients who were very elderly (did you catch that one of them was 101 years old?). They held up well in the real world.

It's important confirmation for a popular and exciting treatment.

A few more ASCO reviews to come soon.