Dr Phillips on the Rationale of Evaluating Glofitamab in R/R Mantle Cell Lymphoma

“Mantle cell lymphoma, especially in a refractory setting, is of interest just because of some limitations and options of especially effective options after patients progress on BTK inhibitors.”

Tycel J. Phillips, MD, MPH, associate professor, Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, discusses the rationale of the phase 1/2 NP30179 trial (NCT03075696) evaluating glofitamab-gxbm (Columvi) monotherapy in relapsed/refractory mantle cell lymphoma (MCL).

The rationale for the MCL portion of the phase 2 trial, data for which were presented at the 2024 ASCO Annual Meeting, was built off the phase 1 portion of the study, Phillips explains. Phase 1 established the safety of glofitamab in patients with different subtypes of relapsed/refractory non-Hodgkin lymphoma. In part 3 of the trial, dose-expansion cohorts were designed for several relapsed/refractory patient populations, including those with MCL.

Of note, treatment with fixed-duration glofitamab in patients with relapsed/refractory MCL led to durable responses, which also included those who were previously treated with BTK inhibitors. Data from the trial presented at the 2024 ASCO Annual Meeting demonstrated an overall response rate (ORR) of 85.0% in all evaluable patients (n = 60), including a complete response (CR) rate of 78.3%. Patients who previously received BTK inhibitors (n = 31) had an ORR and CR rate of 74.2% and 71.0%, respectively. These respective rates were 96.6% and 86.2% in those who were BTK inhibitor-naive (n = 29).

The median duration of response (DOR) and duration of CR were 16.2 months (95 CI, 12.6-not evaluable [NE]) and 15.4 months (95% CI, 12.7-NE), respectively. Patients previously treated with BTK inhibitors had a median DOR and duration of CR of 12.6 months (95% CI, 7.4-NE) and 12.6 months (95% CI, 5.4-NE), respectively.

Updated data presented at the 2024 ASH Annual Meeting showed at a median follow-up of 24.2 months (range, 0-50), evaluable patients with relapsed/refractory MCL (n = 60) achieved an ORR of 82% and a CR rate of 77%.

The need for more treatment options in the relapsed/refractory setting for patients with MCL was a key reason for this study, as there are limited treatment options after patients experienced disease progression on BTK inhibitors, Phillips concludes.