Bispecific Antibodies Expand Treatment Options for Relapsed or Refractory DLBCL in Practice

Key Clinical Summary

• Bispecific antibodies (BsAbs) such as glofitamab, epcoritamab, and mosunetuzumab provide off-the-shelf immunotherapy for relapsed or refractory diffuse large B-cell lymphoma (DLBCL), redirecting T cells to CD20-positive lymphoma cells and offering an alternative for patients unable to receive CAR T therapy or transplant.
• In third-line monotherapy studies, glofitamab (complete response [CR] 39%, overall response rate [ORR] 52%), epcoritamab (CR 40.1%, ORR 63.1%), and mosunetuzumab (ORR 42%, CR 24%) showed meaningful activity; cytokine release syndrome (CRS) was the most common toxicity but generally low grade.
• Combination regimens (eg, glofitamab-GemOx, epcoritamab-GemOx) improved survival and response rates, and emerging data indicate BsAbs can be delivered safely in community oncology settings, expanding access for patients with relapsed DLBCL.

BsAbs are expanding treatment options for relapsed or refractory DLBCL and appear feasible to deliver safely in community oncology settings, offering an important alternative for patients who cannot access CAR T or transplant, according to a study published in Lymphatics.

DLBCL is the most common B-cell lymphoma, but 20% to 40% of patients develop relapsed or refractory disease, with a median overall survival of about 6 months in high-risk cases. Although CAR T therapy and autologous stem cell transplant are key options, many patients are ineligible due to rapid disease progression, limited access to specialized centers, or socioeconomic barriers. This has increased interest in “off-the-shelf” bispecific antibodies, which redirect T cells to target CD20-positive lymphoma cells and can be deployed more quickly and broadly than CAR T.

Three leading BsAbs are now central to the treatment landscape: glofitamab, epcoritamab, and mosunetuzumab. In third-line monotherapy, glofitamab produced a 39% CR rate and 52% ORR in 171 patients, with median overall survival (OS) of 11.5 months. Epcoritamab, studied in 157 patients, achieved a 40.1% CR and 63.1% ORR, with median OS of 18.5 months. Mosunetuzumab showed somewhat lower activity in 88 treated patients, with 42% ORR and 24% CR, and median OS of 11.5 months. CRS was the most common toxicity across all 3 drugs, although it was usually low grade.

Combination regimens are also showing promise. In the phase 3 STARGLO trial, glofitamab plus gemcitabine/oxaliplatin improved outcomes over rituximab-GemOx in transplant-ineligible patients, with median OS of 25.5 months versus 12.9 months, median progression-free survival (PFS) of 13.8 vs 3.6 months, and CR rates of 58.5% vs 25.3%. In the EPCORE NHL-2 study, epcoritamab plus GemOx produced an 85% ORR and 61% CR, with median OS of 21.6 months. Mosunetuzumab plus polatuzumab vedotin also performed well, with 59.2% ORR, 45.9% CR, median OS of 23.3 months, and median PFS of 11.4 months.

The review also shows that BsAbs can be safely implemented in community settings. A California program reported outcomes and toxicity like clinical trials, with most CRS events grade 1-2, no grade ≥3 CRS, and no treatment discontinuations. As trials move these agents earlier in treatment and toward outpatient use, BsAbs may become a more accessible option for relapsed DLBCL.

“BsAbs are effective and accessible treatment options for R/R DLBCL and can be implemented in the community setting,” concluded the study authors.

Reference

Atiga C, Abdulhaq H. A review of bispecific antibody therapy for relapsed/refractory diffuse large B-cell lymphoma and implementation in a community hospital. Lymphatics. 2026;4(1):3. doi:10.3390/lymphatics4010003.