Sequential targeted therapy for anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma: a case report

ALK-positive diffuse large B-cell lymphoma (ALK+ DLBCL) is a rare and highly aggressive lymphoma with poor response to conventional chemotherapy and no established standard treatment. The article describes a case of a 41-year-old male with ALK+ DLBCL harboring a TFG-ALK rearrangement who was sequentially treated with ALK kinase inhibitors (alectinib, ensartinib, lorlatinib, and brigatinib). The patient demonstrated rapid but transient responses to individual ALK inhibitors and subsequently underwent hematopoietic stem cell transplantation. Despite initial success, the disease relapsed four months after transplantation with extensive pulmonary involvement, leading to respiratory failure and death. The case demonstrates both the potential and limitations of sequential ALK inhibitor therapy, which induces rapid tumor regression but responses are not durable and resistance emerges rapidly.