Impact of recent chemotherapy exposure on overall survival in patients with diffuse large B-cell lymphoma receiving bispecific antibody therapy.

Abstract

e19093 Background: Diffuse large B-cell lymphoma (DLBCL) is cured with first-line chemoimmunotherapy, yet nearly 40% of patients develop relapsed/refractory (R/R) disease. Bispecific antibodies (BsAbs) such as glofitamab and epcoritamab improve outcomes in heavily pretreated R/R DLBCL and are being investigated with chemotherapy in earlier lines. The impact of chemotherapy combined with BsAbs on survival and immune toxicities is not well defined. Methods: Retrospective cohort study using de-identified electronic medical record data from the TriNetX network (data through Jan 2026). Adults ≥18, who were diagnosed with DLBCL identified via ICD-10-CM or ICD-O codes (C85.80, C83.30, 9680/3), receiving glofitamab and/or epcoritamab were grouped by receipt of chemotherapy within 90 days (index event), controlled for number of prior lines of therapy (LOT). To minimize confounding, 1:1 propensity score matching (PSM) greedy nearest neighbor, (0.1 caliper) was performed on demographics and key comorbidities. Primary endpoint was overall survival (OS) through 3 years. Secondary endpoints included cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), as defined and graded per the ASTCT criteria. Results: A total of 763 patients met the inclusion criteria; including 284 who received chemotherapy within 90 days of the index event and 479 who did not. After PSM: n=252 per cohort with balanced covariates. Patients in the recent chemotherapy cohort demonstrated a significantly inferior 3-year survival probability compared to the non-chemotherapy cohort (35.7% vs. 46.3%; p = 0.0102). Recent chemotherapy was also associated with higher absolute risk of CRS grade 1–2 (8.7%; p=0.028), and grade >3 CRS (11.5%; p=0.006), as well as ICANS grade 1–2 (5.2%; p=0.038); whereas there was no difference in ICANS grade >3 (5.6% vs 4.4%; p=0.54) [Table 1]. Conclusions: Among adults with DLBCL treated with glofitamab/epcoritamab, chemotherapy within 90 days of BsAb initiation was associated with inferior 3-year OS and increased risk of CRS and ICANS. These findings potentially inform practice, optimal therapy sequencing, and pave the way for future BsAb clinical trials. Overview of recent chemotherapy vs. no chemotherapy prior to bispecific antibody therapy analysis. Category Parameter Chemotherapy Cohort Non-Chemotherapy Cohort Hazard Ratio Absolute Risk Difference p-value Cohort Before Matching 284 479 - - - Cohort After Matching 252 252 - - - Overall Survival (OS) 3-Year Survival Probability 35.67% 46.34% 1.425 - 0.0102 Safety CRS (grades 1-2) 31.75% 23.02% - 8.73% 0.0280 CRS (grades 3-5) 40.08% 28.57% - 11.5% 0.0065 ICANS (grades 1-2) 11.11% 5.95% - 5.16% 0.0382 ICANS (grades 3-5) 5.56% 4.36% - 1.19% 0.5383