ASH 2023 | Extended follow-up of glofitamab monotherapy in R/R LBCL: durability of CR and likelihood of CRS

So today I presented, in an oral session, another round of results from a long-standing Phase I/II study of glofitamab in B-cell lymphomas. In the pivotal Phase II cohort, concentrating on large B-cell lymphoma patients with relapsed/refractory disease, with minimum two prior lines of treatment, were just over 150 patients included. We presented and published on these patients previously, and this is the background for a recent approval, both in North America and in Europe, and several other regions, including Japan, for the treatment with glofitamab in that space, also post-CAR-T. So why was it an oral again here at ASH?

Well, it’s because we’ve updated the durability of the responses. So we see that, even with a median follow-up of complete response, which is seen in 40% of patients, where we have a median follow-up of almost two and a half years of these patients, we see that still at this late stage in follow-up, approaching a median of two years, for all patients, more than half of the complete responses are maintained. And that’s interesting because glofitamab is designed a little bit differently than the competing bispecifics, in that it’s given for a fixed duration of time and a maximum of 12 three-weekly cycles equaling 8.3 months. So when a patient reaches the CR and stays in CR for two years or longer, it means that almost 75% of that time has been without any treatment. Is that equal to cure? It suggests that at least a proportion of these patients probably are cured, even though it’s still a little bit too early to say.

In this analysis we also look at prognostic features, not only for response and benefit, but also for toxicity. And what we did was we measured the so-called total metabolic tumor volume, which is essentially the volume of disease as measured by a PET-CT scan at the beginning of treatment. And we found that those patients who had less than the median tumor burden were less likely to reach a response and the response would be less durable, whereas the highest benefit was seen in the patients who were easier to treat, so the ones with the lower tumor burden. So high tumor burden, poor chance of a lasting response, lower tumor burden, higher chance of a lasting response, which is not really a surprise. This is what you see if you give chemotherapy as well.

But interestingly, we could also split the patients not only in two categories but in four quartiles and look at the potential value in predicting cytokine release syndrome, which is the major side effect for these immunotherapies typically occurring during the first four weeks of treatment. Why is that important? Well, particularly important here in America because they do not like hospitalizing their patients, and that has been a demand in this study because of the risk of cytokine release syndrome. But we can see that a substantial risk of a cytokine release syndrome that requires a hospital facility, that is what we call grade two or higher, is practically only seen in patients with high tumor burden. So the majority of patients with a medium-to-low tumor burden can probably, from now on, be treated in a completely outpatient setting.

We also have another interesting finding. We have approximately one out of three patients in this study previously exposed to a CAR-T, so they have failed a CAR-T prior to entering this study. What we see is that not only are the response rates more or less the same in the prior CAR-T exposed patients as those who are CAR-T naive, but also the durability of the responses that we see are more or less the same as in the general population.