Successful salvage therapy with glofitamab followed by selinexor maintenance in an elderly patient with primary refractory diffuse large b-cell lymphoma harboring TP53 and CD58 mutations: a case report and literature review

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive B-cell lymphoma characterized by pronounced heterogeneity. Patients with relapsed/refractory (R/R) disease after standard R-CHOP regimen face an extremely poor prognosis with subsequent salvage lines. Although chimeric antigen receptor T-cell (CAR-T) therapy represents a breakthrough option for R/R DLBCL, its clinical utility is frequently constrained by various real-world factors in elderly patients. As an alternative T-cell-engaging modality, CD3×CD20 bispecific antibodies (BsAbs) have demonstrated robust efficacy in R/R DLBCL. Herein, we report a 70-year-old male with primary refractory DLBCL harboring co-existing TP53 and CD58 mutations. The patient was refractory to prior lines of therapy, including R-CDOP(rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone), R-GemOx(rituximab, gemcitabine, and oxaliplatin), a BTK inhibitor (zanubrutinib, 160 mg bid), and Pola-BR regimen (polatuzumab vedotin, bendamustine, and rituximab). Remarkably, he achieved a sustained CR following 12 cycles of glofitamab monotherapy and subsequent the XPO1 inhibitor selinexor maintenance, complicated solely by a manageable tumor flare reaction (TFR). This case suggests that glofitamab, potentially followed by targeted maintenance, offers a promising, highly effective, and manageable treatment strategy for elderly patients with ultra-high-risk, multi-line refractory DLBCL.