Introduction The CD20xCD3 bispecific antibodies (BsAbs), epcoritamab (Epco) and glofitamab (Glofi), have emerged as effective therapies for relapsed/refractory (RR) B-cell non-Hodgkin lymphomas (B-NHL), demonstrating high response rates in clinical trials. However, efficacy in the off-trial setting remains limited, especially in populations who would be ineligible for pivotal studies. We conducted a single-center retrospective analysis of patients with B-NHL treated with Epco or Glofi as standard of care (SOC).

Methods We retrospectively reviewed patients with histologically confirmed B-NHL who received at least one dose of either Epco or Glofi as SOC at Moffitt Cancer Center between June 1st, 2023, and May 1st, 2025. Baseline variables included age at BsAb initiation, sex, ECOG performance status (PS), histologic subtype, number of prior lines of therapy (LOT), and prior CAR-T. BsAb exposure, clinical response, and survival status were recorded. Patients were followed until death or last clinical contact. The progression-free survival (PFS) and overall survival (OS) were calculated from BsAb initiation to progression, death, or last follow-up. Survival analyses were conducted using Kaplan-Meier methods, and Cox proportional hazards models were used to evaluate associations between clinical variables and PFS/OS.

Results We analyzed a total of 81 patients with R/R B-NHL, 37 (46%) received Epco and 44 (54%) received Glofi. The median age was 70 years (range: 22–92), with 16% of patients aged ≥80. The cohort was predominantly male (60%) and White (85%). The majority (82%) had diffuse large B-cell lymphoma (DLBCL), followed by high-grade B-cell lymphoma (HGBCL, 14%), and others (5%). At BSAb initiation, 97% had Ann Arbor stage III–IV, 38% had ECOG ≥2, and 26% had double/triple-hit lymphoma, 27% had CD20-negative disease. Transformed lymphoma and CNS involvement were noted in 30% and 17%, respectively.

Patients were heavily pretreated: the median number LOTs was 4, with 72% received ≥3 lines. Prior therapies included CAR T-cell therapy (49%), anthracycline-based regimens (95%), and anti-CD20 monoclonal antibodies (100%). Comorbidities were common: coronary artery disease and arrhythmia (30%), diabetes (22%), and heart failure (13%).

Eleven percent started on BsAb as inpatient due to lymphoma-related complications. Only 16% of patients would have met pivotal trial inclusion criteria. Most common causes of ineligibility were: cytopenia (61%), ECOG ≥ 2 (38%), CNS involvement (17%), inpatient status (11%), clinically significant heart failure (13%) and abnormal renal function (9%).

The best ORR the whole group was 37% (CR 25%). The ORR and CR rates for Epco and Glofi were 32% (CR:24%), 41% (CR:25%), respectively.

At median follow-up time of 12 months, mPFS for the whole cohort was 3.1 months (95% CI, 2.1-5.6); 1-year PFS was 26% (95% CI, 18-39). Median overall survival (OS) was 9.3 months (95% CI, 5.2-N.E.), with a 1-year OS of 46% (95% CI, 35-61). There was no statistical difference of PFS and OS between Epco and Glofit.

Trial-eligible patients (n=13) had a mPFS of 13.5 months (95% CI, 5.6-N.E.) and 1-year PFS of 51% (95% CI, 30-89) and 1-year OS of 70% (95% CI, 48-100). Inpatient status at BsAb initiation (n=9) had poor outcomes: mPFS 1 month (95% CI, 0.7–N.E.), and 6-month PFS and OS were 0%. Trial-ineligible patients treated as outpatient (n=59) had intermediate outcomes with mPFS of 3.2 months (95% CI, 2.1–5.4), 1-year PFS of 25% (95% CI, 15-40), mOS of 6.9 months (95% CI, 4.1-N.E.) and 1-year OS of 44% (95% CI, 32-60). The differences were statistically significant (PFS: p=.0005; OS: p=.04, log-rank test).

In multivariate analysis, male sex (PFS: HR=2.7, p=.004; OS: HR=3.0, p=.006), poor ECOG performance status (PFS: HR=1.47, p=0.04; OS: HR=1.72, p=.01), trial non-eligibility (PFS: HR=1.8, p=.15; OS: HR=3.4, p=.04), inpatient status (PFS: HR=5.0, p=.006; OS: HR=3.9, p=.1) were independently associated with inferior survival. Other variables, including age, prior therapy lines, IPI score, double/triple-hit status, transformed lymphoma and prior CAR-T, were not significant predictors of survival.

Conclusion: In this analysis, Epco and Glofi demonstrated efficacy in a high-risk, heavily pretreated patient population with B-NHL in the SOC setting. Male sex, poor PS, trial non-eligibility for pivotal trials, and inpatient BiAbs administration were correlated with poor survival outcomes.

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2025
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