The monoclonal antibody glofitamab showed durable complete remission (CR) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to study results presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
Among patients treated with at least two prior therapies – including anti-CD20 and anthracycline therapies, and many with chimeric antigen receptor (CAR) T-cell therapy – 39.4% of patients achieved CR and 51.6% had a response overall, according to findings from phase II research presented by Michael Dickinson, MBBS, D.Med Sci, of Peter MacCallum Cancer Centre in Melbourne, Australia.
One benefit of the drug is that it’s given for a fixed amount of time – for a maximum of 12 cycles – and is ready to be administered off the shelf.
“Most patients don’t want to be on treatment indefinitely,” Dr. Dickinson said. “Many like the idea of having a horizon to their treatment duration.”
Given that the median time to response was 42 days, the drug is still given for a considerable length of time after the response, he added, helping to consolidate it.
The trial included 155 patients with DLBCL who had either relapsed after or been refractory to at least two previous therapies. Patients were given glofitamab at a starting dose of 2.5 mg on the first day of the first cycle, increasing to 10 mg on the eighth day of the first cycle, and then to the target dose of 30 mg on the first day of the second cycle. To mitigate cytokine release syndrome (CRS), patients were given the anti-CD20 monoclonal antibody obinutuzumab before starting on glofitamab.
Glofitamab is a bispecific monoclonal antibody with a two-to-one structure, with bivalency for CD20 on B cells and monovalency for CD3 on T cells.
“In preclinical experiments, that substantially increased the potency of the drug, and that’s probably got to do with the capacity of the antibody to bring T cells into closer proximity to their target,” Dr. Dickinson said.
About one-third of the patients had previously been treated with CAR T-cell therapy, and the responses among those patients were similar to the responses overall, with 35% achieving CR.
“That suggests that glofitamab is an important option for patients who’ve relapsed after the CAR T,” Dr. Dickinson said.
Among those who achieved CR, the median duration of the response had not yet been reached, but 77.6% were durable at 12 months.
When researchers looked back at earlier cohorts, those who had been treated with a dose less than the recommended dose but more than 10 mg had a median CR duration of 34.2 months.
“I now have patients who have retained a CR for years, so we think that glofitamab is delivering, if not cure, then certainly durable remissions,” Dr. Dickinson said.
The most significant adverse event was CRS, but it was mostly limited to grade 1, was predictable, and was limited usually to the first cycle of treatment, which allowed providers to counsel patients beforehand. Dr. Dickinson said patients were managed successfully with steroid therapy and, if necessary, tocilizumab.
The drug manufacturer has submitted for regulatory approval in Europe and expects to submit for approval in the U.S. later this year.
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Dickinson M, Carlo-Stella C, Morschhauser F, et al. Glofitamab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and ≥ 2 prior therapies: Pivotal phase II expansion results. Abstract 7500. Presented at the American Society of Clinical Oncology Annual Meeting; Chicago, Illinois.
