Bispecific Antibodies for Older Adults with Aggressive B-cell Lymphomas

People with aggressive B-cell lymphomas who are unable to tolerate full-dose chemotherapy as their first treatment need different options. For people age 65 and older, co-existing conditions are more common. These are conditions other than cancer that can affect a person’s health. Often, the side effects of standard chemotherapy are worse due to these conditions, making it an unsafe treatment option. Learn findings from four studies presented at the 2025 ASH conference that tested safer bispecific antibody combinations for these patients.  

Mosunetuzumab as a first treatment for lymphoma patients unable to receive chemotherapy 

Mosunetuzumab (Lunsumio, Genentech) is a bispecific antibody. This type of treatment connects T cells, a type of immune cell, to lymphoma cells. This helps the immune system target the cancer. 

The phase 2 MorningSun study tested injectable mosunetuzumab as a first treatment for 49 people with aggressive B-cell lymphomas who were unable to receive standard chemoimmunotherapy. After step-up dosing was finished in cycle one, mosunetuzumab was given once each 21-day cycle for a median of 14 cycles. 

After treatment: 

• 73.5% of patients experienced a response to treatment, meaning the lymphoma was reduced 
• 59.2% experienced a complete response, meaning the lymphoma was not seen on scans
• 12 months since experiencing a response, treatment continued to control the cancer for 84.6% of patients 

Most side effects were manageable with supportive care. Injection site reactions were common but usually mild. Cytokine release syndrome (CRS), an immune reaction that can cause fever and low blood pressure, occurred in 12.2% of patients. CRS was low-grade, and all cases resolved. No serious brain-related immune side effects were reported. 

For people with lymphoma who cannot tolerate chemotherapy, the bispecific antibody mosunetuzumab, given for a set period of time, may be a good outpatient treatment option. 

Read this abstract: 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 

Epcoritamab alone for newly diagnosed large B-cell lymphoma

Epcoritamab (Epkinly, Genmab/AbbVie) is another bispecific antibody. The EPCORE DLBCL-3 study included 66 people with newly diagnosed large B-cell lymphoma (LBCL) who were not eligible for full-dose chemotherapy. After step-up dosing in the first cycle, patients received one injection of epcoritamab per cycle for up to 12 cycles.  

Results showed:

• 70% of patients experienced a response to treatment
• 58% experienced a complete response
• 12 months after experiencing a response, treatment continued to control the cancer for 72% of patients

Minimal residual disease, or MRD, was also measured. MRD refers to very small amounts of lymphoma that may remain after treatment. Among those who experienced a response, 88% had no detectable MRD in blood testing. MRD negativity was linked to longer lymphoma control.

Cytokine release syndrome occurred in 70% of patients. Most cases were mild and happened during the first cycle. Some patients had temporary brain-related side effects. 

For people living with LBCL who are not candidates for full-dose chemotherapy, the bispecific antibody epcoritamab may provide many patients with long-lasting responses. 

Read this abstract: Fixed-duration epcoritamab monotherapy induces high response and MRD-negativity rates in elderly patients with newly diagnosed large B-cell lymphoma (LBCL) and comorbidities: Results from EPCORE DLBCL-3  

Epcoritamab plus R-mini-CHOP

R-mini-CHOP is a lower-dose version of standard chemotherapy given to people with LBCL who are unable to tolerate full-dose chemotherapy. In the EPCORE NHL-2 study, epcoritamab was added to R-mini-CHOP for 28 people with newly diagnosed LBCL who were unable to receive full-dose chemotherapy because of age or co-existing health conditions. Treatment was given over the course of 8 cycles, then stopped.  

Findings from the study showed: 

• 89% of patients experienced a response to treatment
• 86% experienced a complete response
• 2 years after experiencing a response, the treatment was still working to control cancer for 78% of patients 

MRD negativity was seen in 95% of patients, including those with higher-risk disease. Serious infections affected 29% of patients, mostly during early treatment cycles. Eleven percent of patients discontinued treatment from side effects. This shows that the majority of side effects were able to be managed with supportive care, helping patients finish treatment. 

For people with LBCL who were unable to receive full-dose chemotherapy, adding epcoritamab to R-mini-CHOP as a first treatment helped patients more than R-mini-CHOP by itself. 

Read this abstract: Epcoritamab + R-mini-CHOP results in 2-year remissions and high MRD negativity rates in elderly patients with newly diagnosed DLBCL: Results from the EPCORE NHL-2 trial

R-Pola-Glo for people with B-cell lymphomas

Another phase 2 study tested R-Pola-Glo for 80 people with aggressive B-cell lymphomas who were unable to tolerate full-dose chemotherapy. This regimen included the monoclonal antibody rituximab, a targeted therapy called polatuzumab vedotin (Polivy, Genentech), and the bispecific antibody glofitamab (Columvi, Genentech). Treatment was given for 12 cycles. 

The study showed: 

• 90% of patients experienced a response to treatment
• 81% experienced a complete response
• 1 year since the start of treatment, 90% of patients were alive 

Cytokine release syndrome affected 31% of patients. Most cases were mild, happened in early cycles, and all resolved. Another common side effect that patients experienced was infections, with 22% of cases being serious and requiring supportive hospital management. 

These findings show that the combination of rituximab, polatuzumab vedotin, and glofitamab helped the majority of patients experience a response to treatment and improve survival. 

Read this abstract: Phase II frontline chemolight R-pola-glo trial induces high and durable response rates in elderly and medically unfit/frail patients with aggressive B-cell lymphoma  

What this means for you

Across these studies, bispecific antibodies by themselves and in combinations showed promising results for people with aggressive B-cell lymphomas who were unable to receive full-dose chemotherapy as their first treatment. Ask your lymphoma specialist if one of these newer approaches or a clinical trial may be right for you.

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