This article reports the multidisciplinary team (MDT) management of an elderly patient with primary refractory diffuse large B-cell lymphoma (DLBCL) complicated by multiple comorbidities, including hypertension, coronary atherosclerosis, aortic sclerosis, and diabetes. Upon admission, the patient was diagnosed with advanced-stage DLBCL. Based on tolerance assessment, first-line immunochemotherapy (R-CHOP regimen) was initiated but showed suboptimal efficacy. Subsequently, a Bruton's tyrosine kinase inhibitor (BTKi) was added guided by next-generation sequencing (NGS) results, achieving partial response after four cycles. However, disease progression occurred following two additional cycles. After MDT discussion, a bridging therapy combining targeted therapy and radiotherapy was implemented, followed by sequential chimeric antigen receptor T-cell immunotherapy (CAR-T), ultimately leading to complete remission sustained for over one year. This case highlights the challenges in managing elderly patients with primary refractory DLBCL and underscores the value of a multidisciplinary collaborative approach.