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Sequential targeted therapy for anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma: a case report
Guocheng Zhong1, Yiran Wang1, Tian Zhang2
1Department of Hematology and Oncology, International Cancer Center, Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University Health Science Center, Shenzhen, China.
Background:
Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma (ALK + DLBCL) is a rare and highly aggressive mature B-cell lymphoma with poor responses to conventional chemotherapy and no established standard treatment. Although ALK inhibitors have shown potential activity in ALK-rearranged malignancies, their clinical utility and optimal sequencing in ALK + DLBCL remain unclear.
Case Presentation:
We report a 41-year-old male patient diagnosed with ALK + DLBCL harboring a TFG-ALK rearrangement. The patient experienced progressive disease during the clinical course and showed rapid, although transient, responses to sequential ALK inhibitor therapy. Subsequent chemotherapy-based salvage regimens provided only limited disease control. The patient received sequential ALK-directed therapy with alectinib, ensartinib, and lorlatinib, followed by a short brigatinib rechallenge before transplantation. These ALK inhibitor-based treatments provided intermittent disease control over more than one year. After lorlatinib followed by combination chemotherapy and a short brigatinib rechallenge, the patient proceeded to hematopoietic stem cell transplantation (HSCT). However, the disease relapsed four months after transplantation, with rapid and extensive bilateral pulmonary involvement, ultimately leading to respiratory failure and death.
Conclusion:
This case highlights both the clinical utility and limitations of sequential ALK inhibitor therapy in ALK + DLBCL. A short brigatinib rechallenge was also attempted before transplantation, although its objective efficacy could not be established because of the limited treatment duration. Sequential targeted therapy may induce rapid tumor regression and help bridge patients to HSCT; however, responses are not durable, resistance can emerge rapidly, and post-transplant relapse may remain highly aggressive. More effective combination or consolidation strategies are needed to improve long-term outcomes in this rare lymphoma subtype.
