TOPLINE

Subcutaneous mosunetuzumab combined with polatuzumab vedotin was associated with a complete response in more than half of older patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who were classified as unfit or frail in a phase 1/2 trial. However, infections, including fatal cases mostly related to COVID-19, were the major safety concern, particularly among frail patients.

METHODOLOGY

• Older or unfit patients with DLBCL cannot tolerate standard chemotherapy, and about 25% of those aged 80 years or older receive no lymphoma treatment. Mosunetuzumab with polatuzumab vedotin showed a 70% objective response rate in relapsed disease, prompting testing of this chemotherapy-free combination as first-line therapy.
• Researchers conducted a multicenter, open-label phase 1/2 trial evaluating subcutaneous mosunetuzumab in combination with polatuzumab vedotin in 108 previously untreated patients with DLBCL or high-grade B-cell lymphoma classified as unfit (58%) or frail (41%) by simplified geriatric assessment; 101 participants (median age, 81 years) treated at full dose were included in the efficacy analysis.
• Participants received six cycles (each lasting 21 days) of combination therapy — polatuzumab vedotin (administered intravenously on day 1 of each cycle) plus subcutaneous mosunetuzumab — followed by two cycles of mosunetuzumab alone, for a planned total of eight cycles. Mosunetuzumab was given using step-up dosing in cycle 1 (5 mg, 45 mg, and 45 mg on days 1, 8, and 15, respectively,  in the full-dose cohorts) and at 45 mg on day 1 of each subsequent cycle.
• The primary outcome was objective response rate at the end of treatment, assessed by an independent review committee. Secondary outcomes included complete response rate, best objective response rate, duration of complete response, progression-free survival, and overall survival.  The median follow-up duration was 36.5 months.

TAKEAWAY

• The objective response rate at end of treatment was 61.4%, and the complete response rate was 56.4%; the best observed objective response rate during treatment was 80.2%.
• By independent review, median duration of complete response was 30.3 months and median progression-free survival was 32.1 months; an estimated 72.1% of complete responders remained in complete response at 2 years. The 2-year progression-free survival was 54.7%, and 2-year overall survival was 62.4%.
• Among 108 patients, adverse events occurred in 107 (99.1%). Cytokine release syndrome (CRS) occurred in 30.6%, predominantly grade 1 (23.1%), with grade 3 events in 1.9%; all CRS episodes cleared after a median of 2 days, and none caused patients to discontinue therapy.
• Infections were reported in 51.9% of patients, including grade 3 or higher events in 23.1%; fatal adverse events occurred in 16.7% of participants, with 55.6% of these deaths related to COVID infection; 80% of COVID fatalities occurred in participants classified as frail at baseline.

IN PRACTICE

"The results support the feasibility of immunotherapy-based first-line strategies in selected geriatric participants and suggest that combinations of bispecific antibodies with antibody-drug conjugates may provide durable disease control in a subset of individuals," the authors of the study wrote.

SOURCE

The study, led by Adam J. Olszewski, Rhode Island Hospital in Providence, Rhode Island, was published online in Blood.

LIMITATIONS

The single-arm design precluded direct comparison with standard chemotherapy regimens. The study enrolled participants during the COVID pandemic, which contributed to treatment discontinuations and infection-related mortality, particularly among frail participants. Heterogeneity across international sites in healthcare systems may have influenced outcomes.

DISCLOSURES

The study was sponsored by F. Hoffmann-La Roche Ltd. Five authors reported being employed by Genentech, Inc., and two by F. Hoffmann-La Roche Ltd. Five authors reported holding stock in F. Hoffmann-La Roche Ltd. Multiple authors reported consulting fees, advisory board roles, speakers bureau participation, or research funding from F. Hoffmann-La Roche Ltd and various pharmaceutical companies including AbbVie, Takeda, Gilead, BeiGene, AstraZeneca, Janssen, and others. Full author disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.