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Patients with high-grade B-cell lymphoma (HGBCL), who are in early relapse or primary refractory, always have poor outcomes. Even intensive chemotherapy or CAR-T cell therapy is not always the best solution. Here is a case of refractory high-grade B-cell lymphoma with MYC, BCL2, and BCL6 rearrangements (triple-hit HGBCL), who achieved complete metabolic remission (CMR) following six cycles of glofitamab monotherapy induction and followed by autologous stem cell transplantation (ASCT) consolidation. The patient has achieved a sustained CMR and a progression-free survival (PFS) of 25 months (ongoing) from progression. Hepatitis B virus (HBV) seroconversion occurred during ASCT before stem cell engraftment, and was effectively suppressed with entecavir. Immune function was monitored in our case by flow cytometry. Downregulation of PD-1 expression on T cells and a reduced proportion of regulatory T cells (Tregs) were observed, consistent with fully activated immune function, which may explain why the patient responded rapidly and maintained durable efficacy. Immune analysis also exhibited B cell subset exhaustion and a disrupted naïve/memory T cell ratio which suggested an immunosenescence phenotype. It is speculated that an over activation of immune function promotes immunosenescence following bispecific antibody therapy, this needs attention. This case highlights the potential of glofitamab induction followed by ASCT consolidation to achieve durable remission in aggressive triple-hit HGBCL. The immune function after bispecific antibody treatment should be monitored and needs further investigation.