Glofitamab Yields High Responses in Small R/R Mantle Cell Lymphoma Cohort

In this phase 1/2 study, patients with relapsed/refractory mantle cell lymphoma received a step-up dose of glofitamab escalating from 2.5 mg to 30 mg plus obinutuzumab pretreatment at 1000 mg or 2000 mg.

A fixed treatment duration of glofitamab-gxbm (Columvi) produced a high rate of complete responses (CRs) in a small population of patients with heavily pretreated relapsed/refractory mantle cell lymphoma (MCL), according to findings from a phase 1/2 trial (NCT03075696).

The overall response rate (ORR) and complete metabolic response (CMR) rate in all patients receiving glofitamab monotherapy (n = 37), respectively, was 83.8% and 73.0%. Among those previously treated with Bruton tyrosine kinase (BTK) inhibitor therapy (n = 24), the corresponding rates were 75.0% and 66.7%, respectively.

Additionally, in those who received glofitamab step-up dosing plus 1000 mg of obinutuzumab (Gazyva; n = 16) the ORR and CMR were 75.0% and 62.5%, respectively; the corresponding rates were 90.5% and 81.0%, respectively, in those treated with step-up dosing plus 2000 mg of obinutuzumab. Moreover, in the subgroup that previously received a BTK inhibitor and went on to receive the 1000 mg and 2000 mg doses of obinutuzumab, respectively, the ORR and CMR were 63.6% and 54.5%, as well as 84.6% and 76.9%.

Investigators reported a median time to first response of 51 days (range, 29-234). Moreover, the CR rate was 48.6% and the ORR of 73.0% at the time of first assessment. Among patients with responses at end of treatment, there were no instances of progressive disease beyond this point.

As of the data cutoff point, 20 of 27 patients with a CR (74.1%) experienced sustained remission. Additionally, the median duration of CR was not reached; excluding 4 deaths due to COVID-19, and 87% of CRs were enduring.

In this phase 1/2 study, patients received a step-up dose of glofitamab escalating from 2.5 mg to 30 mg plus obinutuzumab pretreatment at 1000 mg (n = 16) or 2000 mg (n = 21). Investigators evaluated responses based on Lugano 2014 criteria and cytokine release syndrome (CRS) events per American Society for Transplantation and Cellular Therapy guidelines.

Patients 18 years and older with histologically confirmed relapsed/refractory MCL and at least 1 prior line of systemic therapy were eligible for inclusion on the trial. An ECOG performance status of 0 or 1 was another requirement for enrollment.

The median patient age was 72.0 years (range, 41.0-84.0) in the overall population. In the 1000 mg and 2000 mg of obinutuzumab pretreatment groups, respectively, most patients were male (81.3% and 66.7%) and had stage III or IV disease at study entry (100.0% and 85.7%). Additionally, most patients in each respective cohort received a prior BTK inhibitor (68.8% and 61.9%) and were refractory to any prior line of treatment (93.8% and 85.7%).

All patients (100.0%) experienced any-grade adverse effects (AEs). In the 1000 mg and 2000 mg obinutuzumab cohorts, respectively, serious AEs affected 81.3% and 76.2% of patients, and grade 3/4 AEs occurred in 87.5% and 52.4%. Additionally, grade 5 AEs were observed in 19.0% of patients assigned to receive 2000 mg of obinutuzumab pretreatment. The most common AEs related to glofitamab included CRS (73.0%), neutropenia (43.2%), anemia (21.6%), aspartate aminotransferase increases (21.6%), and fatigue (18.9%).

Any type of CRS event affected 87.5% and 66.7% of patients pretreated with 1000 mg and 2000 mg of obinutuzumab, respectively. In each respective cohort, the rates of serious CRS events were 62.5% and 23.8%, and the median time to CRS onset was 7.55 hours (range, 4.4-14.0) and 9.77 hours (range, 5.0-20.8). Investigators highlighted 1 instance of immune effector cell-associated neurotoxicity syndrome (ICANS) in the 2000 mg pretreatment cohort that was resolved.

Other common any-grade AEs of interest included infections and infestations (64.9%), neurologic AEs (48.6%), and neutropenia (45.9%). Investigators also highlighted grade 3 or higher infections and infestations in 32.4% of patients, which included 1 grade 4 instance of endocarditis and grade 5 instances of COVID-19 in 2 and COVID-19 pneumonia in 1.

Investigators reported these findings in a poster presentation at the 2023 Annual Meeting of the Society of Hematologic Oncology (SOHO).

Reference

Phillips T, Dickinson M, Morschhauser F, et al. Glofitamab monotherapy induces high complete response rates in patients with heavily pretreated relapsed or refractory mantle cell lymphoma. Presented at the 2023 Society of Hematologic Oncology (SOHO) Annual Meeting; September 6–9, 2023; Houston, TX. Abstract MCL-467.