Glofitamab Treatment in Relapsed or Refractory DLBCL after CAR T-Cell Therapy

SIMPLE SUMMARY: CAR T-cell therapies represent a major advance in the treatment of relapsed B-cell non-Hodgkin lymphomas. Nevertheless, a significant proportion of these patients will experience disease progression following CAR T treatment. For these patients, no standard therapeutic procedure is established so far. The novel bispecific antibody glofitamab has shown promising activity in the treatment of refractory or relapsed B-cell non-Hodgkin lymphomas. In this study, we provide evidence for good tolerance and promising efficacy of glofitamab administration in patients relapsing after CAR T-cell therapy. ABSTRACT: Chimeric antigen receptor T-cells (CAR T) treatment has become a standard option for patients with diffuse large B-cell lymphomas (DLBCL), which are refractory or relapse after two prior lines of therapy. However, little evidence exists for treatment recommendations in patients who relapse after CAR T-cell treatment and the outcome for such patients is poor. In this study, we evaluated the safety and efficacy of a monotherapy with the bispecific CD20xCD3 antibody glofitamab in patients who progressed after CAR T treatment. We report nine consecutive patients with progressive DLBCL after preceding CAR T-cell therapy. The patients received a maximum of 12 cycles of glofitamab after a single obinutuzumab pre-treatment at an academic institution. CRS was observed in two patients (grade 2 in both patients). We observed an overall response rate of 67%, with four patients achieving a complete response and a partial remission in two patients. Interestingly, we identified increased persistence of circulating CAR T-cells in peripheral blood in three of the five patients with measurable CAR T-cells. Our data suggest that glofitamab treatment is well tolerated and effective in patients with DLBCL relapsing after CAR T-cell therapy and can enhance residual CAR T-cell activity.