Glofitamab monotherapy plus ASCT achieves 25-month durable remission in refractory triple-hit HGBCL

Patients with high-grade B-cell lymphoma (HGBCL), particularly those with MYC, BCL2, and BCL6 rearrangements (triple-hit HGBCL), face extremely poor prognoses when in early relapse or primary refractory states. Current intensive chemotherapy regimens and even advanced CAR-T cell therapy often fail to provide durable responses for these aggressive lymphomas. This creates a critical unmet need for novel therapeutic strategies that can achieve sustained remission and improve long-term survival in this challenging patient population.

This case report details the treatment of a single patient (N=1) with refractory triple-hit HGBCL. The patient received glofitamab monotherapy as induction, specifically six cycles of the bispecific antibody. This induction phase was subsequently consolidated with autologous stem cell transplantation (ASCT). The primary endpoint was the achievement of complete metabolic remission (CMR) and progression-free survival (PFS). Immune function was monitored throughout the treatment via flow cytometry to assess cellular changes and potential mechanisms of response or adverse events.

The patient achieved a complete metabolic remission (CMR) following six cycles of glofitamab monotherapy induction, which was then sustained after ASCT consolidation. This led to a remarkable progression-free survival (PFS) of 25 months (ongoing) from the time of progression. Immune monitoring revealed several key changes: > Downregulation of PD-1 expression on T cells and a reduced proportion of regulatory T cells (Tregs) were observed, consistent with a fully activated immune function, potentially explaining the rapid and durable efficacy. Furthermore, immune analysis exhibited B cell subset exhaustion and a disrupted naïve/memory T cell ratio, suggesting an immunosenescence phenotype. Hepatitis B virus (HBV) seroconversion occurred during ASCT, which was effectively suppressed with entecavir.