Step-Up Dosing Maintains Efficacy, Reduces Adverse Effects of Glofitamab in Large B-Cell Lymphoma

By using a step-up dosing approach, researchers have found that the efficacy of glofitamab can be maintained while reducing some adverse effects in the treatment of patients with large B-cell lymphoma, according to researcher Michael J. Dickinson, MBBS, DMedSci. Dickinson spoke with Pharmacy Times about the findings at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting.

Can you give an overview of glofitamab and its indication for patients with non-Hodgkin lymphoma?

Michael J. Dickinson, MBBS, DMedSci: So, glofitamab is a CD20/CD3 bispecific T cell-engaging antibody, which has a unique 2-to-1 format. It binds 2 CD20 molecules for 1 CD3 molecule. And what it does is it forms a physical bridge between T cells and the target, which is B cells, and in this case lymphoma B cells. And that then leads to T cell activation and the T cells then kill the target cells which are the lymphoma B cells. Glofitamab is given intravenously, and it's given after an initial single dose of obinutuzumab. Obinutuzumab is an anti-CD20 antibody that's currently in routine use in the clinic, and we give a flat dose of 1 gram a week prior to starting glofitamab, which is given in 2 steps up to the target dose of 30 mg, and each of the doses is separated by a week. So, that's the drug in summary.

And we've been doing a phase 1, first in human trial for a number of years now. We've explored a range of B cell histologies in that phase 1 trial and we've presented different sets of data on those different histologies over the last couple of years. But the focus here at ASCO was to present the pivotal data in large B-cell lymphoma. And we included patients with diffuse large B-cell lymphoma not otherwise specified, as well as high-grade B-cell lymphoma and primary mediastinal B-cell lymphoma all in this in this pivotal data set. Patients had to have had at least 2 prior lines of therapy before they could be eligible for this particular clinical trial, and we gave glofitamab for 12 cycles of treatment. So, it's a fixed course treatment. And at the end, here at ASCO, we were able to present the results of that.

And those results showed what we were able to achieve. It's a very difficult to treat population with highly refractory disease [and] a median of 3 prior lines of therapy. [There were] 80% who had been refractory to prior therapies, in fact, 85% had been refractory to prior therapies. We were able to achieve a complete remission rate of 39.4%, which is remarkable for a drug to do. And to put that in the context, you would have expected maybe optimistically, a complete remission rate of around 15% to 20% with standard chemotherapies in that context. And so, for a drug to do this, to be available off the shelf, for patients not to have to wait for that drug, for example, if they might have to wait for CAR T cells to be manufactured, to be able to achieve that complete remission rate is really very exciting for hematologists like me who treat patients with these aggressive lymphomas. And so, I see this as being that potential future option on the basis of this data for patients, really with, you know, all patients with relapsed and refractory large B-cell lymphoma after 2 prior lines.

I guess one of the questions that often comes up is, well, how durable are those remissions? And so, the other piece of data that we were able to present today at ASCO, was that 80% of the patients roughly retain their complete remission at 12 months, even though they stopped treatment at 9 months. So, we think that's going to translate to very durable remissions. And we were able to show a data set of patients treated at lower doses, and it had complete remissions where those responses had been maintained for years. And indeed, in my own practice, I have several patients who've been in complete remissions well beyond 3 years and into their fourth year after being exposed to glofitamab at much lower doses than the dose that we used in in this particular data in in this pivotal data set. So that's all very exciting. It suggests that it will be a real drug that will really, I think, come into practice and be very useful and available for doctors and patients.