Mosunetuzumab Plus Polatuzumab Vedotin Shows Promise in Relapsed/Refractory B-Cell NHL

By Ariel Jones - Last Updated: December 14, 2021

Mosunetuzumab, a bispecific antibody that targets CD20xCD3, was safe and efficacious for patients with heavily pretreated relapsed and/or refractory B-cell non-Hodgkin lymphoma (NHL) when combined with the anti-CD79b antibody drug conjugate polatuzumab vedotin. According to investigator L. Elizabeth Budde, MD, PhD, who presented the research at the 2021 American Society of Hematology (ASH) Annual Meeting, this regimen also was effective in patients who received prior chimeric antigen receptor (CAR) T-cell therapy.
As of March 15, 2021, researchers enrolled 63 patients with relapsed/refractory B-cell NHL, with 22 patients enrolled in the phase Ib dose-escalation cohort and 41 in the phase II dose-expansion group. The median age of all patients was 68 years (range = 20-83). Patients were mostly (62%) male and had the following disease subtypes:
• de novo diffuse large B-cell lymphoma (DLBCL [n=44])
• transformed follicular lymphoma (trFL [n=12])
• grade 3b follicular lymphoma (FL [n=4])
• grade 1-3a FL (n=3)
Patients had received a median of three prior lines of therapy (range = 1-10). Seven patients in the dose-escalation group and 17 in the dose-expansion cohort had previously received CAR T-cell therapy, Dr. Budde noted.
Treatment cycles were a total of 21 days. On day 1 of cycles 1 through 6, patients received polatuzumab vedotin 1.8 mg/kg via intravenous (IV) infusion. During cycle 1, patients received IV mosunetuzumab with step-up dosing to mitigate the risk of cytokine release syndrome (CRS). The recommended phase II dose of mosunetuzumab (1 mg on cycle 1 day 1; 2 mg on cycle 1 day 8; 60 mg on cycle 1 day 15 and cycle 2 day 1; and 30 mg on day 1 of cycles 3-8) was administered. At the end of cycle 8, patients with stable disease or partial response (PR) were permitted to continue mosunetuzumab for a total of 17 cycles. Patients with a complete response (CR) discontinued mosunetuzumab after cycle 8.
In the dose-escalation arm, hospitalization was not required for administration of mosunetuzumab. Patients who experienced disease progression after initial CR could be retreated with mosunetuzumab or mosunetuzumab plus polatuzumab vedotin.
At a median follow-up of 5.3 months (range = 0.7-23.7), the overall response rate (ORR) was 65%. The authors noted that high ORRs were observed among patients with de novo DLBCL (73%) and patients who had previously undergone CAR T-cell therapy (63%). The median duration of response was not reached. Dr. Budde noted that, after an initial CR that lasted for 15 months, one patient had achieved a CR with mosunetuzumab retreatment at data cut-off.
The most common adverse events (AEs) related to treatment with this regimen, occurring in ?25% of patients, were fatigue (38%), peripheral neuropathy (33%), diarrhea (27%), and nausea (25%). Grade 3-4 treatment-related AEs occurring in ?5% of patients were neutropenia (21%) and fatigue (6%), while one patient experienced grade 5 pneumonia associated with mosunetuzumab. CRS was reported in 11 patients, with 10 of the cases being grade 1. Nine patients died of disease progression during the study, while three additional patients died from other causes.
“The phase II dose-expansion cohort continues to enroll patients with relapsed/refractory aggressive B-cell NHL,” Dr. Budde concluded.

Post Tags:ASH 2021 Lymphoma/DLBCL NewsASH Annual Meeting 2021