Early findings show that glofitamab may be a safe and effective option for patients with pretreated, relapsed/refractory B-cell non-Hodgkin lymphoma.
The investigational drug glofitamab showed promising outcomes in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL), according to results from a phase 1 study published in the Journal of Clinical Oncology.
These early findings show that glofitamab may end up being a more attractive option for this group of patients than other currently available CAR-T cell therapies.
“Glofitamab is an available and accessible ‘off-the-shelf’ T-cell–engaging therapy. These properties contrast with those of current CAR-T cell therapies, which require manufacturing, may require bridging therapy, and may not be feasible in patients with rapidly progressive disease,” the study authors wrote.
The trial — which analyzed potential dosing strategies and safety for the drug — included 171 pretreated patients with B-NHL: 90.6% were refractory to prior therapy, with the average amount of prior therapies being three. About three-fourths (74.3%) had diffuse large B-cell lymphoma, transformed follicular lymphoma or other aggressive histology, and the rest of the patients had indolent lymphoma subtypes.
The trial was divided into two parts. Part 1 assessed glofitamab’s efficacy at 0.005 milligrams, 0.015 milligrams, and 0.045 milligrams, but there were no responses at that dose, and all patients withdrew because their disease got worse.
Part 2, however, had better responses, with drug effects starting at the 0.6 milligram dose. At the 25-milligram dose, all patients reported cytokine release syndrome (CRS), so the researchers found that this exceeded the maximum tolerated dose for one day. As a result, moving forward, the researchers established two step-up dosing groups: 2.5 milligrams on cycle 1 day one and 10 milligrams on cycle 1 day 8, then either 16 milligrams or 30 milligrams on cycle 2 day 1. The 30 milligram-dose was decided to be the dose moving forward in phase 2 trials.
Nearly half of patients (49.3%) with aggressive B-NHL had a complete response (CR) – meaning that there was no detectable cancer in their bodies – when given a 10 milligram-dose or higher.
“CRs were achieved rapidly in patient’s high tumor burden, bulky disease, and refractoriness to multiple therapies,” the study authors wrote.
Nearly all (98.2%) of the patients experienced one or more side effect from glofitamab, with the most common being CRS, occurring in 50.3% of patients. A total of 21.5% of CRS was grade 1; 25.1% grade 2; 2.3% grade 3; and 1.2% grade 4.
“CRS was manageable with low rates of grade 3 or higher and moderate use of steroids or tocilizumab with no treatment withdrawals,” the authors wrote. “Events fully resolved in all but one patient who died because of progressive disease before recovery.”
As patients continued to be treated, the number who experienced CRS decreased – 13.1% in cycle 2 and 6.1% in cycle 3 or later. Patients with high disease burden or bone marrow infiltration were more likely to experience CRS.
More research still needs to be done, but for now, glofitamab is showing promising results.
“Glofitamab has demonstrated frequent, durable CRs and a manageable tolerability profile and allows off-the-shelf treatment for patients with refractory B-NHL in need of timely therapy,” the authors concluded.
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