ASH Review: Mosunetuzumab (Bi-Specific) for FL

As I have said a couple of times, there weren't really any game-changing presentations at ASH for Follicular Lymphoma. But the one that I am seeing the most commentary on is for research on the Bispecific treatment called Mosunetuzumab. 

The specific session is "127 Mosunetuzumab Monotherapy Is an Effective and Well-Tolerated Treatment Option for Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Who Have Received ≥2 Prior Lines of Therapy: Pivotal Results from a Phase I/II Study."

To remind you: A bispecific is kind of like a monoclonal antibody (such as Ritixan). It can recognize and attach to a protein on the surface of a cancer cell (like the way Rituxan attaches to CD20). But the bispecific has something extra. The other end also attaches to something -- a T cell, a powerful immune cell (that's the "T" in "CAR-T"). So a bispecific ("bi" means "two) can bring two things together -- a cancer cell and the immune cell that can kill it. 

It's one of those treatments that oncologists get excited about. My own oncologist, Dr. H, has mentioned bispecifics to me a few times. Some say they might be a cheaper alternative to CAR-T treatments, since they use the same immune cells, but don't have to be created specifically for each individual patient. 

The ASH study is fairly small (a phase 1 and 2 trial), but seems to provide some important data about how effective the treatment might be. The patients in the study had relapsed or refractory disease (their last treatment didn't work, or stopped working after a while), and had already tried at least two other treatments.

90 Follicular Lymphoma patients were in the trial, and had already received a wide range of treatments, including chemo, inhibitors, stem cell transplants, and CAR-T.  In total, the Overall Response Rate was 78.9%, with 57.8% getting a Complete Response. Pretty good numbers. Some groups did particularly well, with POD24 (patients whose FL returned within 24 months of getting chemo) having an ORR of 83% and a CR of 55%. The median Progression Free Survival was 17.9 months.

Again, this is a relatively small study, but the numbers for effectiveness look very good. 

Of course, the second part of an early trial is looking at safety -- how bad were the side effects?

The most common Adverse Event was Cytokine Release Syndrome (also very common in CAR-T), though the researchers say most of those reactions were low grade (Adverse Events, or side effects, are grades from 1 to 5, with 1 and two considered low grade, and 3 to 5 being high grade, ore more dangerous. About 42% of patients had grade 1 or 2 CRS, while one patient had grade 3, one had grade 4, and none had grade 5.  Other common side effects included fatigue (36.7%), headache (31.1%), and some low blood counts. Two patients died during the study of causes that were not related to the treatment. Four patients needed to stop treatment due to side effects. The full list of AEs is available on the link to the ASH session.

I'm mentioning all of the AEs/side effects for a couple of reasons. First, I know I tend to not get into as much detail as I should (one of the problems with being a "look on the bright side" kind of person). But also because reader Shelley commented on my last post:

Bob, Have you seen this video, Q&A style, from: Noah Merin, MD, PhD, from the Blood and Marrow Transplantation Program and assistant professor of medicine at Cedars-Sinai Medical Center. I thought bi-specifics might be the next best thing compared to CAR-t, but from what he says about reactions to it, turns me off. I'm sure you've watched/read other specialists view on bio-specifics vs. CAR-T - what's your opinion?
Shelly  

I haven't seen the video, Shelley, and if you can put a link in the comments, I'd appreciate it.

The researcher who presented the data at ASH called the side effects "manageable," using a C1 inhibitor to manage the CRS. (The C1 inhibitor is a treatment that can help slow down CRS and keep the reaction from becoming harmful to the patient). 

I can't say for sure whether the side effects are risky enough to choose another treatment over this one. The commentaries I have read seem to agree with the researcher, and don' think they are serious enough to discount Mosunetuzumab. We need to keep in mind that this is a phase 1 and 2 study, so it's still fairly small, and a larger study might show that the side effects are better (or worse) than for this group of patients. The FDA and other regulators will ultimately decide whether or not the benefits outweigh the risks. 

There will be lots of post-ASH comments in the next few months; I'll be interested to hear what experts have to say about this (if anything). 

In the meantime, Shelley, please send a link to the video. Thanks.