CD20 Levels May Impact BsAb Response in B-Cell Lymphomas

CD20 expression levels were associated with patient outcomes following treatment with bispecific CD20xCD3 antibodies in patients with B-cell lymphomas in a new study. The findings, which were published in Blood Neoplasia, could help clinicians better devise strategies for tackling such cases.¹

Corresponding author Simon Husby, MD, of the University of Copenhagen, and colleagues explained that in CD19-directed chimeric antigen receptor (CAR) T-cell therapy, loss of CD19 has been linked with inferior outcomes among patients with diffuse large B-cell lymphoma (DLBCL).² 

However, research into a similar question—whether pretreatment CD20 expression levels correlate with responses to CD20xCD3 bispecific antibodies—has not been thoroughly investigated, Husby and colleagues noted.¹ One exception, they noted, was a phase 1 study published in 2022. That study found no association between CD20 levels and initial response rates to glofitamab (Columvi; Genentech), a CD20xCD3 bispecific antibody.³

The findings suggest assessment of CD20 may be an important factor in determining treatment options in B-cell lymphomas. | Image credit: kalpis - stock.adobe.com

Husby and colleagues wanted to examine the issue in a larger cohort of patients. They looked at 149 cases of patients with B-cell lymphomas who were given CD20xCD3 bispecific antibodies as part of phase 1/2 trials at 3 Danish healthcare centers between 2017 and 2024.¹ In addition to immunohistochemical analyses of the patients, the authors also examined 60 post-treatment tumor samples.

Most of the patients (n = 100) had DLBCL, 36 had follicular lymphoma, and 13 had other lymphoid neoplasms. Almost all participants (n = 131) received CD20xCD3 bispecific antibodies as monotherapy, though 18 received it as part of a combination regimen. The median follow-up from the first bispecific antibody treatment was 22.2 months.

Patients were stratified into 3 cohorts based on immunohistochemical expression of CD20. Most of the patients (n = 131) were found to have “strong” CD20 expression. Thirteen participants had “reduced” expression, which was defined as weak, heterogeneous, or partial CD20 expression. Five participants had negative CD20 expression, which was defined as a true lack of CD20 expression. Biopsies found to meet the “reduced” or “negative” criteria were reassessed by a team of 4 experienced hematopathologists to confirm the findings of the original pathology reports.

Patients in the “reduced” CD20 cohort had a progression-free survival (PFS) rate of 26% at 12 months (95% CI, 1-51), compared with 53% among participants with strong CD20 expression (95% CI, 44-62). In terms of overall survival (OS), patients with reduced CD20 had a 51% survival rate at 12 months (95% CI, 23-80), compared with a 12-month OS rate of 73% among patients with strong CD20 expression (95% CI, 65-80). None of the 5 patients in the negative CD20 cohort were alive at 12 months.

When the authors analyzed patients based on whether they had aggressive or indolent lymphomas, they continued to find differences in outcomes based on CD20 levels, with superior outcomes for those with normal CD20 expression.

A univariate Cox regression analysis showed reduced CD20 expression was significantly correlated with inferior OS and borderline significantly associated with inferior PFS. When the authors adjusted for age, sex, and Eastern Cooperative Oncology Group performance status, reduced CD20 expression was still significantly associated with inferior OS, though it only trended toward worse PFS.

The findings have important implications for future studies of CD20xCD3 antibodies, the authors explained.

“An important perspective is whether patients with reduced expression of CD20 but strong expression of CD19 may have better outcomes with CAR T-cell therapy or novel trispecific antibodies targeting multiple tumor antigens (for example, both CD20 and CD79),” they wrote.

The authors added that using combinations of different therapies might also be able to overcome the impact of inferior CD20 expression.

More research into those questions is needed, but Husby and colleagues concluded that CD20 expression may be an important factor when considering which treatments to recommend for patients with B-cell lymphomas.

References

1. Kyvsgaard ER, Grantzau TL, Sørensen MD, et al. Reduced CD20 expression yields inferior survival in patients with B-cell lymphoma treated with CD20xCD3 antibodies. Blood Neoplasia. 2025;100096. doi:10.1016/j.bneo.2025.100096.

2. Strati P, Neelapu SS. CAR-T failure: beyond antigen loss and T cells. Blood. 2021;137(19):2567-2568. doi:10.1182/blood.2020010462

3. Bröske AE, Korfi K, Belousov A, et al. Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma. Blood Adv. 2022;6(3):1025-1037. doi:10.1182/bloodadvances.2021005954