ASH 2023 | Updated results of glofitamab plus polatuzumab vedotin combination therapy in DLBCL, including HGBCL

So later today we’re presenting a similar abstract, but it’s in a poster form, and it’s a study where we have given the combination of glofitamab, a CD3 x CD20 bispecific antibody, with polatuzumab vedotin, the CD79b-targeted antibody-drug conjugate, which is already approved in first and later lines and in combination with chemotherapy. So this combination, why?

Well, we want to deepen the already quite good responses to glofitamab in the relapsed/refractory setting and also combine two drugs which have absolutely no overlapping toxicity. The main toxicities of polatuzumab vedotin are cytopenias, that you do see to some extent after glofitamab. But the main one is really neurotoxicity, which is a cumulative toxicity, whereas glofitamab carries with it cytokine release syndrome, typically over with by the end of cycle one. So these are non-overlapping both in time and nature which means they are highly combinable.

Do they work together? Definitely so. Overall responses are seen in approximately 80% of patients, with complete responses in 60% approximately. And this is despite an enrichment of this cohort of 125 patients, with almost one third of patients being high-grade B-cell lymphoma, a relatively rare but very difficult to treat patient group. We enriched the cohort with these patients because for 6 to 9 months we only had inclusion of high-grade B-cell lymphoma patients, just to to get a proper number. What do we see in that sub-cohort? Slightly lower response rate, 73% overall, complete responses in 57%, but it’s still better than we’ve seen in any Phase I/II study in this difficult space before.

What about these responses, are they durable? They are as durable at least as glofitamab monotherapy. And of course, the more patients you get to respond, the more difficult it is to maintain these responses because you have more patients that you need to maintain and keep active on the immunotherapy. The immune surveillance, as we call it, needs to be active. What do we see? Well, after a follow-up which is at a median of just under two years, we see that the patients who managed to get to a CR and again, that’s approximately 60% of patients, even after, with the follow-up of the complete response, so a duration of the complete response, looking at 15, 18 months after the first occurrence of the complete response, that means more than one year out from the stopping of treatment, still way more than 50% of the complete responses are maintained. It’s in the order of 70% long-term towards the end of the follow-up that we have at this point.