By Mary Ellen Schneider
Single-agent mosunetuzumab appeared effective and well tolerated as first-line treatment for elderly and unfit patients with diffuse large B-cell lymphoma (DLBCL) in an early-phase trial, according to findings presented at the annual meeting of the American Society of Hematology.
In the ongoing phase 1-2, open-label study, researchers assessed the safety and efficacy of the bispecific monoclonal antibody mosunetuzumab among patients with untreated DLBCL or high-grade B-cell lymphomas who were not eligible to receive standard chemo-immunotherapy because they were at least 80 years old or had a comorbidity that made them unable to tolerate a full dose of chemo-immunotherapy (Abstract 401).
“The efficacy we observed is quite encouraging, with almost two-thirds of patients achieving response and about 45% of patients achieving complete response to single-agent treatment without any chemotherapy exposure,” said Adam J. Olszewski, MD, of Brown University in Providence, R.I., who presented the study findings.
Dr. Olszewski said the researchers wanted to investigate the use of a chemotherapy-free option since some older patients are unable to tolerate chemoimmunotherapy regimens and trials of reduced-dose regimens have produced inferior survival outcomes in this group of patients. “Treatment of diffuse large B-cell lymphoma, among patients who are elderly or unfit, remains an active area of clinical need,” he said.
Researchers enrolled 29 patients in the study and responses to treatment were assessed after four and eight cycles of therapy. The study population was mostly elderly, with a median patient age of 82 years. Other patients had functional or organ impairments and about half of patients had advanced-stage disease.
Among 22 efficacy-evaluable patients, 63.5% of patients achieved a response and 45.5% achieved a complete response. Patients who achieved complete response did so by the time of the initial assessment after four cycles of therapy and all have maintained their response through the end of eight cycles, Dr. Olszewski reported. There is also preliminary evidence of durability of response, with the first patients maintaining a complete response more than 10 months after the end of therapy, he said.
The toxicity profile of mosunetuzumab was also favorable in the study. The treatment-related adverse events were mostly related to cytokine release syndrome and infusion reactions, with rare fatigue and gastrointestinal adverse events. Just 14% of patients experienced any serious treatment-related adverse events (grade 3-4) and there have been no fatal adverse events and no adverse events leading to treatment discontinuation. In total, 7% of patients developed grade 3-4 neutropenia and 7% of patients experienced grade 3-4 infections. Six patients experienced cytokine release syndrome, all which resolved within 1-2 days.
The researchers also observed T cell activation in all patients, but there was no clear association with response, Dr. Olszewski said.
“These data pave the way to potentially explore chemotherapy-free or chemotherapy-light regimens that could be used for treatment of first-line diffuse large B-cell lymphoma, particularly in the population of elderly and unfit patients, as well as for the use of mosunetuzumab as a potential anti-CD20 backbone for future combinations,” Dr. Olszewski said.