Relapse Is Uncommon in Patients with Large B-Cell Lymphoma Who Are in Complete Remission at the End of Fixed-Course Glofitamab Treatment

Abstract

Background: Glofitamab, a CD20xCD3 T-cell-engaging bispecific monoclonal antibody with a novel 2:1 (CD20:CD3) configuration, redirects T cells to eliminate normal and malignant B cells. Glofitamab is an off-the-shelf treatment, administered intravenously (IV) for a fixed duration of 12 cycles. In pivotal expansion cohorts of an ongoing Phase I/II study (NP30179; NCT03075696), glofitamab has demonstrated a manageable safety profile and induced frequent and durable complete responses (CRs) in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL; Dickinson et al. ASCO 2022). Here, we present data for the duration of CR from end-of-treatment (EOT) in patients with R/R LBCL enrolled in the dose escalation and expansion phases of this study. Methods: Patients with R/R LBCL with ≥1 prior line of therapy (diffuse large B-cell lymphoma not otherwise specified [DLBCL NOS], high-grade B-cell lymphoma [HGBCL], primary mediastinal large B-cell lymphoma [PMBCL] or transformed follicular lymphoma [trFL]) were enrolled. Patients received 1000mg obinutuzumab pre-treatment 7 days prior to first dose of glofitamab, followed by IV glofitamab for up to 12 cycles (8.4 months). Glofitamab was given at a fixed dose (0.6-25mg) or with step-up dosing (target dose: 16mg or 30mg) every three weeks. Responses were assessed using Lugano 2014 criteria (Cheson et al. J Clin Oncol 2014). Results: As of March 14, 2022, 61/214 (29%) patients with R/R LBCL who had received glofitamab at a dose of ≥0.6mg, including suboptimal doses, were in CR by investigator assessment at EOT by intent-to-treat analysis (DLBCL, n=41; trFL, n=18; HGBCL, n=1; PMBCL, n=1). Median age was 67 years (range: 22-85), and 51% were female. The median number of prior lines of therapy was 3 (range: 2-9), and the majority of patients (61%) had received ≥3 prior therapies. Overall, 43% of patients were refractory to their initial therapy, and 74% were refractory to their most recent regimen. The median duration of CR follow-up was 18.1 months (95% confidence interval [CI]: 14.8-20.7). Fifty-three patients had reached 6 months follow-up post-EOT; the majority of patients with a CR at EOT (45/61; 74%) remained in CR, 1/61 (2%) had experienced progressive disease (PD), and 8/61 (13%) remained in follow-up but had not yet reached 6 months. At 12 months post-EOT, 34/61 (56%) patients remained in CR, 1/61 (2%) had experienced PD, and 17/61 (28%) remained in follow-up but had not yet reached 12 months. One patient experienced PD between 12 and 18 months post-EOT (Figure). Forty-six percent of patients had been in follow-up long enough to reach their 18-month post-EOT visit, and 20% of patients had reached their 42-month post-EOT visit. The median duration of CR had not been reached. Of the three patients who experienced PD after having a CR at EOT, one patient had initiated re-treatment at the time of the analysis and achieved a second CR. Five patients discontinued the study (two received an allogeneic transplant, two due to physician decision, one lost to follow-up). Five patients died (one due to secondary malignancy, two due to PD, two for unknown/other reasons). Conclusions: Most patients with LBCL who achieved a CR at EOT experienced durable responses in the absence of continued treatment. Only 1 of 44 patients who reached 12 months follow-up post-EOT experienced progression. Longer follow-up is needed to further confirm the off-treatment durability of glofitamab-induced CRs in patients with R/R LBCL beyond the 12-month timepoint. It is particularly encouraging that off-treatment progression was rarely observed in this heavily pre-treated, largely treatment-refractory, LBCL patient population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal