KEY TAKEAWAYS
- Glofitamab, a bispecific antibody that recruits T cells to tumor cells, was evaluated in a phase 1-2 study for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had received at least two lines of therapy previously.
- Pretreatment with obinutuzumab was used to mitigate cytokine release syndrome, followed by fixed-duration glofitamab monotherapy for 12 cycles.
- The primary end point was complete response according to assessment by an independent review committee, with a secondary end point of duration of response, survival, and safety.
- At a median follow-up of 12.6 months, 39% of patients had a complete response, with consistent results among those who had previously received chimeric antigen receptor T-cell therapy.
- Adverse events, particularly cytokine release syndrome, occurred in the majority of patients, with 9% discontinuing glofitamab due to adverse events. However, the therapy was found to be effective for DLBCL, with 78% of complete responses ongoing at 12 months and a 12-month progression-free survival of 37%.
Diffuse large B-cell lymphoma (DLBCL) patients with relapsed or refractory disease have a dismal outlook. The bispecific antibody globitumab attracts T lymphocytes to tumour cells.
They recruited patients with relapsed or refractory DLBCL who had previously been treated with at least 2 other lines of treatment for the phase 2 portion of a phase 1-2 investigation. Patients were given obinutuzumab before fixed-duration glofitamab monotherapy to reduce the severity of cytokine release syndrome (12 cycles total). As determined by an external review board, the key outcome measure was a full response. The duration of the reaction, survival, and safety were all important secondary outcomes.
There were 155 individuals enrolled, and 154 of them received at least one dose of a study therapy (obinutuzumab or glofitamab). The independent evaluation found that 39 percent of patients had a full response at a median follow-up of 12.6 months (95% CI, 32 to 48). The 52 patients who had tried chimeric antigen receptor T-cell treatment before (35% of whom had a full response) all had similar outcomes. Complete responses occurred on average after 42 days (95% CI: 42-44). By the 12-month mark, 8 out of 10 replies were still active. After a year, 37% of patients were still progression-free (95% CI, 28 to 46).
About 9 percent of patients stopped taking glofitamab because of side effects. Cytokine release syndrome was the most common serious side effect, occurring in 63% of patients. Sixty-two percent of patients experienced grade 3 or higher adverse events, including 3% neurologic problems and 4% cytokine release syndrome. In cases of diffuse large B-cell lymphoma, treatment with glofitamab proved successful. Almost 50% of patients experienced a serious adverse event of grade 3 or 4.
Source: https://pubmed.ncbi.nlm.nih.gov/36507690/
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT03075696/
Dickinson, M.J., Carlo-Stella, C., Morschhauser, F., Bachy, E., Corradini, P., Iacoboni, G., Khan, C., Wróbel, T., Offner, F., Trněný, M., Wu, S.-J., Cartron, G., Hertzberg, M., Sureda, A., Perez-Callejo, D., Lundberg, L., Relf, J., Dixon, M., Clark, E. and Humphrey, K. (2022). Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. New England Journal of Medicine, 387(24), pp.2220–2231. doi:https://doi.org/10.1056/nejmoa2206913.
