ASH 2021 | Glofitamab and obinutuzumab in r/r MCL

The study I will discuss through the next few minutes, to report this data on the use of glofitamab in patients with relapse and refractory mantle cell lymphoma. And it has been recently presented at the ASH meeting by Tycel Phillips. Mantle cell lymphoma is an aggressive subtype of B-cell non Hodgkin lymphoma. Patients with relapsed and refractory mantle cell lymphoma have a poor prognosis, particularly when they progress after therapy with BTK inhibitors. Glofitamab is a T-cell-engaging bispecific antibody with a novel two-to-one molecular configuration, characterized by two binding sites for CD20 and one binding site for CD3. It has been reported earlier this year, in a paper published in the Journal of Clinical Oncology, glofitamab with obinutuzumab pretreatment has a promising efficacy and a manageable safety In patients with AVD pretreated relapse or refractory B-cell non Hodgkin lymphoma. In this study, it’s clearly shown that obinutuzumab pretreatment at 1000 milligrams and/or step-up dosing at cycle one, have a clinically significant mitigation of cytokine release syndrome. Here, in this specific study, we have got preliminary data from the NP30179 phase one/two trial. Patients with relapse and refractory mantle cell lymphoma who received 1000 milligram or 2000 milligram doses of obinutuzumab prior to glofitamab monotherapy. Based on PK findings, regarding the clearance of obinutuzumab, we expect that a higher dose of obinu prior to glofitamab step-up dosing could further reduce the risk of CRS in mantle cell lymphoma. So far, 29 patients with relapse and refractory mantle cell lymphoma have received glofitamab. In particular, patients received glofitamab at fixed dosing after 1000 milligrams obinutuzumab. Seven patients received glofitamab step-up dosing after 1000 milligrams obinutuzumab. And 19 patients received glofitamab step-up dosing after 2000 milligrams obinutuzumab. The median age in this patient population was 69 years, with 83% of the patients having stage three/ four disease. Patients were already pretreated, and in fact, they had received a median of three prior lines of therapy. 69% of them had been pretreated with BTK inhibitors, and 90% of the patients were refractory to any prior therapy. In terms of efficacy, overall, glofitamab data resulted in a high response rate in patients with relapse and refractory mantle cell lymphoma. And in fact, the overall response rate in the 21 patients which were evaluated for efficacy was 81%, with 67% experiencing a complete metabolic response. Similar response rates were observed in patients who had received prior BTK inhibitor therapy versus patients who had not. Interestingly, 86% of the patients who actually had a complete response had ongoing remissions at the data cut off. Safety could be evaluated in 29 patients. And these analyses show that the most common adverse events were CRS, experienced by 59% of the patients, and infusion-related reactions which were detected in 24% of the patients. All cytokine release syndromes were grade one or two by ASTCT criteria, except for one patient who experienced a grade one CRS. Interestingly, CRS rates were substantially lower in the cohort receiving 2000 milligrams obinutuzumab pretreatment plus step-up dosing. And in this cohort, the CRS rate was 47%, whereas the rate of CRS was 71% in the cohort receiving 1000 milligrams obinutuzumab followed by step-up dosing glofitamab. So in conclusion, we can say that glofitamab used at a fixed duration of treatment, demonstrated a promising efficacy and a favorable safety in relapse and refractory mantle cell lymphoma. Glofitamab at step-up dosing induced a high response rate in patients with relapse and refractory mantle cell lymphoma, most of whom had failed a prior BTK inhibitor therapy. CRS was manageable and mostly low grade. Based on these considerations, glofitamab continues to be evaluated in the post BTK inhibitors relapse and refractory mantle cell lymphoma safety. And these results will support a future confirmatory trial. Thank you for listening.