Mosunetuzumab induces complete remissions in poor prognosis non-Hodgkin lymphoma patients
Prof Stephen Schuster - University of Pennsylvania, Philadelphia, USA
The study I presented at this meeting is an early phase trial of a bispecific antibody called mosunetuzumab. This bispecific antibody is a T-cell and B-cell engager – it has receptors for CD20 on B-cells, CD3 on T-cells and by engaging these cells, bringing these cells together, initiates cell mediated, T-cell mediated, cytotoxicity to B-cells and depletes B-cells. So the study included 270 patients with relapsed or refractory B-cell lymphomas and used this agent to exploit this mechanism of action to treat the malignancies.
These patients were a heavily pre-treated group of patients in two broad categories – indolent lymphomas and aggressive lymphomas. Most of the aggressive lymphomas were either large B-cell lymphoma or transformed follicular lymphoma to large cell. Most of the so-called indolent arm lymphoma patients had follicular lymphoma, kind of a misnomer indolent because these were heavily pre-treated patients that weren’t responding to their last therapy. Inclusion criteria were such that these were patients that didn’t have standard therapeutic options available to them, they’d been through the standard therapies.
Overall excellent response rates in both arms of the study with a good safety profile, a roughly 40% overall response rate in the aggressive arm, roughly a 60% overall response rate in the indolent arm. In patients with complete response in both arms therapy was able to be discontinued and three-quarters of those patients in the aggressive arm at about 17 months and the indolent arm at 24 months have been able to remain off therapy without any additional treatment.
Now, there were four patients who had recurrence of their disease and those patients were re-treated and three out of the four responded to re-treatment and one of the four actually had a complete response that’s ongoing as well. So it’s exciting, a new agent which is capable of inducing remissions in patients beyond the standard of care. Even 30 patients on that trial had had prior CAR T-cell therapy which is the latest approach to this group of patients and represent a group of patients which have had everything and yet we had a similar response rate in those patients as we had in patients that hadn’t had prior CAR T-cell therapy and no unforeseen safety concerns.
What is the unmet need for patients who don’t respond to CAR T-cell therapy?
CAR T-cell therapy was the therapy that we used for patients with B-cell malignancies as a last resort, this was five years ago with regard to lymphomas and a little longer with regard to leukaemias. With regard to lymphomas, which are the diseases I treat in the study that I’m discussing, we were able to save about a third of those patients with a CAR T-cell approach. These are patients that in the past had no other options and would not have survived. Now we have five years of follow-up on those patients and we know that we can save a third of them. So now we’re looking at the other two-thirds that we were not able to save and what can we do. In that setting, in that group, we’ve tested mosunetuzumab and it will serve in part that population that still has an unmet need even in the CAR T-cell era.
What’s next?
I see a very bright future for this particular drug and an even brighter future for the patients that will be able to benefit from it. I see combinations of this with CAR T-cell therapy; sequences of this for patients that need immediate therapy because it’s off the shelf to be followed by CAR T-cell therapy or patients who are getting CAR T-cell that are not responding that can be rescued by this agent or doing them in sequence up-front either way or both ways because you can target more than one antigen this way without doing any fancy genetic manipulation of cells or anything like that. Relatively speaking to the technologies that are in development nowadays, this is a relatively simple approach.
