Key Clinical Summary:

• Design/Population: A prospective study evaluated mosunetuzumab, an anti-CD20-CD3 bispecific antibody, among 50 elderly patients with previously untreated diffuse large B-cell lymphoma (DLBCL) who were unfit for chemoimmunotherapy; median age 82 years (range, 76 to > 100).
• Key Outcomes: Overall response rate was 70%, with 50% achieving complete responses, many associated with MRD negativity; CRs were durable at a median follow-up of 12.5 months. Cytokine release syndrome occurred in 12% (grade 1 or 2 only), no ICANS observed, and therapy was delivered entirely outpatient without mandatory hospitalization.
• Clinical Relevance: Mosunetuzumab demonstrated meaningful efficacy with a favorable safety profile in treatment-naive, elderly DLBCL patients lacking standard options, supporting further development as a potential alternative to R-mini-CHOP in this high-comorbidity population.

Jeff Sharman, MD, Willamette Valley Cancer Institute and Research Center, Eugene, Oregon, presented results evaluating mosunetuzumab as frontline therapy for elderly, treatment-naive patients with diffuse large B-cell lymphoma (DLBCL) who are unfit for standard chemoimmunotherapy at the 2025 ASH Annual Meeting & Exposition.

In these interim results from the phase 2 MorningSun study, Mosunetuzumab achieved an overall response rate of 70%, with about 50% complete responses, many of which were MRD-negative and durable at a median follow-up of 12.5 months.

Dr Sharman concluded, “I think there's going to be a very active effort to see if we can replace R-mini-CHOP in the elderly patients with future studies.”

Transcript:

Hi, my name is Jeff Sharman. I practice at the Willamette Valley Cancer Institute and Research Center in Eugene, Oregon, and I'm a member of the Sarah Cannon Research Institute. We had the honor to present on behalf of our co-investigators the treatment effect, that’s both safety and efficacy, of mosunetuzumab amongst elderly patients with diffuse large B-cell lymphoma who'd never previously been treated.

Mosunetuzumab is an anti-CD3-CD20 bispecific antibody. It's approved currently for patients with relapsed or refractory follicular lymphoma in the third line space where it's demonstrated considerable activity. We wanted to treat elderly large cell lymphoma patients to see how it worked. Part of the reason for this is there is no defined effective standard of care for patients who are unfit for chemoimmunotherapy. While R-CHOP or R-mini-CHOP, I should say, is commonly utilized, many patients aren't eligible for it on account of their medical comorbidities.

We enrolled about 50 patients. The median age in the study was 82 years old. The range was 76 to over 100. We had centenarians in the study. Mosunetuzumab was administered with some dexamethasone during cycle 1 and 2 to mitigate for cytokine release syndrome. It was given in a step-up dose on day 1 at 5 mg, and then 45 mg on days 8 and 15, followed by 45 mg every 3 weeks for up to 1 year.

We were very pleased that we had an overall response rate of around 70%. About half of patients had complete response (CR) and those complete responses in many cases were associated with MRD negativity. At least during the period of observation, those patients who achieved CR maintained those CRs. Now, the median follow-up on the study was about 12 and a half months, so longer follow-up will be necessary to really validate the effectiveness of the therapy.

Safety was really quite impressive. This class of drugs is associated with cytokine release syndrome (CRS). We saw that only in 12% of patients. There were, I believe, 4 episodes of grade 1 and a single episode of grade 2. Immune effector cell-associated neurotoxicity syndrome (ICANS) was not seen at all. This therapy was administered entirely in the outpatient setting. No mandatory hospitalization was required. We did see a number of infections, which is fairly typical for this population, but we didn't necessarily see an excessive safety signal for this.

This is a promising therapy in this space and the overall session that it was in looked at the number of studies that had similar design, bispecific antibodies in treatment-naive, elderly, large-cell lymphoma. I think there's going to be a very active effort to see if we can replace R-mini-CHOP in the elderly patients with future studies.

Source:

Sharman J, Tun A, Bisneto JV, et al. Fixed treatment duration subcutaneous mosunetuzumab monotherapy in elderly/unfit patients with previously untreated diffuse large B-cell lymphoma: Interim results from the phase II MorningSun study. Dec 6-9, 2025; Orlando, FL. Abstract: 62