Michael Dickinson, MBBS, on DLBCL: Phase II Expansion Results on Glofitamab
Michael Dickinson, MBBS, of the Peter MacCallum Cancer Centre, the Royal Melbourne Hospital, and The University of Melbourne, discusses new data, which showed that fixed-duration glofitamab induces durable complete remissions with a favorable safety profile in patients with or refractory diffuse large B-cell lymphoma and two or more prior therapies, including exposure to CAR T cells (Abstract 7500).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Glofitamab is a full-length CD20/CD3 bispecific T-cell engaging antibody, which is unique from its two to one structure, which delivers potency. It's given intravenously after a single dose of obinutuzumab a week later. We start with glofitamab 2.5 milligrams, then 10 milligrams, and then 30 milligrams, and then it's given once every three weeks for 12 cycles.
We presented data of this approach in 154 patients with relapsed and refractory large B-cell lymphoma after at least two prior lines of therapy. We included patients with transformer lymphoma, double-hit lymphoma, and diffuse large B-cell lymphoma, NOS and also primary mediastinal B-cell lymphoma. In this population, there is a real area of need. Although CAR T cells are available, not everyone can access CAR T cells. We included patients, however, who'd previously had CAR T cell. In fact, 30% of the population that was recruited had been exposed to CAR T cell, and almost all of those patients had been refractory.
Indeed, 80% of the overall population were refractory to prior therapies when they went into this trial and were exposed to glofitamab. Strikingly then, we were able to demonstrate a complete remission rate of 39.4%. Complete remissions are crucial to deliver durable remissions in large B-cell lymphoma, and we saw that approximately 80% of patients had retained their complete remission at 12 months. This is striking because glofitamab is given for a fixed course. In fact, it's unique amongst the bispecifics in that way. Some bispecifics are given indefinitely, whereas glofitamab is given for a fixed course of 12 cycles. So when we looked at patients in 12 months and saw that they're retaining their complete remission, this was clinically significant.
There were some toxicities which relate to the mechanism of action of the bispecific antibodies. We saw cytokine release syndrome in just over 60% of patients, but this reduced to 50% of patients when we used dexamethasone routinely as a premedication during the step-up phase. Cytokine release syndrome was almost universally low-grade beyond the first dose of treatment. In fact, when we used dexamethasone in this way, we saw no grade 2 cytokine release syndrome beyond the first dose of glofitamab.
We also presented a population of patients who'd been recruited earlier during the phase I trial treated for the same inclusion criteria, but at a lower dose than the phase II dose of glofitamab. This meant that we could look at what happens to patients who have complete remissions who were followed for beyond the median 12 months in the pivotal cohort. In this supportive cohort, we had a median follow up of 2 years, and we had 35 patients who'd achieved a complete remission. What we saw is that very, very few patients relapse beyond the 12 month mark. So when we take these two pieces of information together, we can conclude that glofitamab delivers a clinically significant rate of complete remissions, that the therapy is deliverable, with an acceptable rate of cytokine release syndrome that is very manageable, and also that these complete remissions are durable even though the treatment stops after 12 cycles given 3 weeks apart. So at about the 9 month mark.
This means that this is a really important treatment option for patients. If this becomes widely available, it can be applied to patients who have relapsed or refractory disease, it can be applied to patients who relapse after CAR T-cell therapy, and it's deliverable in a way that can be easily managed by patients and physicians as an off-the-shelf treatment.
Barbara Eichhorst, MD, of the German CLL Study Group and the University of Cologne, discusses phase III findings from the GAIA/CLL13 trial, which showed that time-limited treatment with venetoclax, obinutzumab, and ibrutinib or venetoclax plus obinutzumab improved progression-free survival compared with standard chemoimmunotherapy in fit, previously untreated patients with chronic lymphocytic leukemia (Abstract LBA2365).
Harry P. Erba, MD, PhD, of Duke Cancer Institute, discusses potentially practice-changing phase III results from the QuANTUM-First trial, which showed that adding quizartinib to standard chemotherapy and up to 3 years of continuation therapy led to improvement in overall survival for adults aged 18 to 75 with newly diagnosed FLT3-ITD–positive acute myeloid leukemia. The manageable safety profile further supports the use of quizartinib in combination with standard therapy, including allogeneic hematopoietic stem cell transplantation, in this setting (Abstract S100).
Nicholas J. Short, MD, of The University of Texas MD Anderson Cancer Center, discusses updated results from a phase II study that suggests the chemotherapy-free regimen of simultaneous ponatinib and blinatumomab is safe and effective in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia. For patients with newly diagnosed disease, stem cell transplantation does not appear to be needed in first remission (Abstract S114).
Anna Sureda, MD, PhD, of the University of Barcelona and the Catalan Institute of Oncology, discusses phase III clinical and patient-reported outcomes from the ZUMA-7 trial, which showed that axicabtagene ciloleucel was superior to second-line standard-of-care treatment in patients 65 years or older with relapsed or refractory large B-cell lymphoma (Abstract S211).