The Lynx Group

First-Line Mosunetuzumab Safe and Effective in Older Patients with Diffuse Large B-Cell Lymphoma

February 2021, Vol 12, No 1

Single-agent mosunetuzumab is a safe and clinically promising chemotherapy-free therapy for elderly and unfit patients with untreated diffuse large B-cell lymphoma (DLBCL), said Adam J. Olszewski, MD, Associate Professor of Medicine, Brown University, Providence, RI, at ASH 2020. Dr Olszewski reported the results of a phase 1/2 clinical study of mosunetuzumab in patients with DLBCL.

“This was the first study, to our knowledge, using a single-agent bispecific antibody as a potentially curative therapy for previously untreated diffuse large B-cell lymphoma,” he said.

Observational studies show that up to 30% of patients aged ≥75 years may not receive standard chemoimmunotherapy regimens. In this setting, clinicians typically prescribe attenuated regimens because of concerns for comorbidities, geriatric syndromes, and adverse events.

“The treatment of diffuse large B-cell lymphoma among patients who are elderly or unfit remains an active area of clinical need,” Dr Olszewski said.

Mosunetuzumab is a fully humanized immunoglobulin G1 anti-CD20 and anti-CD3 bispecific antibody that redirects T-cells to engage and eliminate malignant B-cells. As a single agent, mosunetuzumab showed promising efficacy and acceptable safety in patients with relapsed and refractory lymphoma, including DLBCL.

The study presented by Dr Olszewski evaluated the safety and efficacy of mosunetuzumab monotherapy among elderly or unfit patients with DLBCL in the first-line setting.

The ongoing phase 1/2 study enrolled untreated patients with DLBCL or with hybrid B-cell lymphomas, including double- or triple-hit lymphomas. Dr Olszewski highlighted that this was a challenging patient population, with a median age of 82 years. Approximately 50% of the patients had stage IV disease plus increased lactate dehydrogenase.

Encouraging Efficacy

Because mosunetuzumab can cause cytokine release syndrome during the first cycle, patients initially received a step-up dosing regimen. The full assigned dose was given on day 1 of each subsequent 21-day cycle, for a total of 8 treatment cycles. The first safety cohort received 13.5-mg doses, and additional patients received 30 mg. The safety was first assessed after 4 cycles, with the final assessment after 8 cycles.

Among all 22 patients evaluable for efficacy, the response rate was 63.5%, including 45.5% complete responses. By dose of mosunetuzumab, responses were seen in 75.0% of patients who received 13.5 mg and 57% treated with 30 mg, of which 37.5% and 50.0%, respectively, were complete responses.

“This is quite encouraging for single-agent mosunetuzumab,” Dr Olszewski noted, adding that no differences in response were observed by dose.

At a median follow-up of 5.4 months, preliminary evidence of durable responses has been observed. Patients who had a complete response did so early in the study, at the time of the interim assessment, and all have maintained the response to the final assessment.

“The first patient enrolled achieved a complete response and has now been off treatment for more than 10 months,” Dr Olszewski said. “Of the 10 patients with progressive disease, 9 have received salvage therapy postprogression and are still alive. Of the 4 efficacy-evaluable patients with double- or triple-hit lymphomas, 2 are in complete response.”

Safety Profile

Only 14% of patients had any treatment-related grade 3 or 4 adverse events, including neutropenia (7%) and infections (7%). None were fatal or have led to treatment discontinuation.

The rate of cytokine release syndrome was 21%, and almost all cases were grade 1. One grade 2 event included fever, hypotension, tachycardia, tachypnea, and chills and resolved without tocilizumab (Actemra) or steroids.

Immediately after the first infusion, the pharmacodynamic assessment showed evidence of T-cell activation, but no clear association was seen between peripheral T-cell activation and response. Some pharmacodynamic effects continued to be observed at later cycles, although at a reduced magnitude.

“These data pave the way to potentially exploring chemotherapy-free or chemotherapy-light regimens that could be used first-line for treating DLBCL, particularly in elderly and unfit patients, as well as for the use of mosunetuzumab as a potential anti-CD20 backbone for future combinations,” Dr Olszewski said.

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