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Michael Dickinson, MBBS, on Clinical Implications of New Findings on Glofitamab for DLBCL

Posted: Monday, June 27, 2022

Michael Dickinson, MBBS, of the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and The University of Melbourne, discusses what could be a promising therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the bispecific monoclonal antibody glofitamab. Given that these patients have been heavily pretreated, including with CAR T cells, Dr. Dickinson offers clinical pearls on administering glofitamab and managing side effects, including neurotoxicities.

Transcript

Disclaimer: This video transcript has not been proofread or edited and may contain errors.

Glofitamab is a CD20 CD3 T-cell-engaging bispecific antibody. We recently presented the results of this antibody treatment in relapsed and refractory large B-cell lymphoma after two prior lines. In the population that was recruited, at the phase two go forward dose, we were able to demonstrate a complete remission rate of 39.4%. This is striking because 80% of patients who were included in the trial had refractory disease and 30% had previously been treated with CAR T cells, almost all of those patients had been refractory to the CAR T cell therapy. Glofitamab is given as an intravenous treatment. It's unique amongst the bispecific antibodies because it's given for a fixed duration. We give Obinutuzumab as a single flat dose to mitigate cytokine release syndrome. We give one gram a week before the first dose of Glofitamab. The target dose of Glofitamab is 30 milligrams, and it's reached in two steps separated by a week; 2.5 milligrams, a week later 10 milligrams, a week later 30 milligrams. We then give 30 milligrams once every three weeks out to a fixed course of 12 cycles and then stop. In the trial, the complete remissions were achieved usually by around 40 days, which is the first response assessment in the trial. So complete remissions are achieved very rapidly on this drug. We did see cytokine release syndrome, which is a consequence of the T-cell activating mechanism of action. But we learned is that if we give Dexamethasone prior to Glofitamab, we only see cytokine release syndrome in about 50% of patients, and in the vast majority that's grade one cytokine release syndrome. All grade two cytokine release syndrome was limited to the first step-up dose of Glofitamab when we used Dexamethasone prior to Glofitamab. It comes on at a very reliable time at about 10 hours post the end of the infusion, which means that physicians can plan and counsel the patient about the possibility of developing a fever in the period after Glofitamab infusion. We are developing a risk score, which enables us to identify patients who are at risk of cytokine release syndrome. But it's very reassuring that cytokine release syndrome is mainly grade one or grade two and is manageable with Dexamethasone and Tocilizumab, and usually limited to that first step-up dose. What's unique about Glofitamab and that sets it apart from some of the other bispecific antibodies is this idea that it can be given for a fixed course and that it stops at 12 cycles. 80% of patients retained their complete remission at the 12 month follow up mark when we looked at the outcome of patients with complete remission. When we looked at our patients who had been treated before the phase two go forward dose was established, and what happened to those patients who achieved complete remission, we actually see very few relapses beyond the 12 month mark. So here we have a treatment that is active in patients who've relapsed or refractory after CAR T cells, active in patients with refractory disease to other prior therapies, deliverable with a fixed course of therapy, we can counsel the patients about when their treatment is going to finish, and deliverable with acceptable toxicity profile that is predictable and very manageable. I should mention that neurotoxicity that we see in CAR T cells is vanishingly rare with this bispecific as well and not a practical problem in routine use.



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