Secondary Diffuse Large B-Cell Lymphoma After Sequential Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid...

Tyrosine kinase inhibitors (TKIs) targeting the BCR::ABL1 fusion protein have revolutionized the treatment of chronic myeloid leukemia (CML), transforming it into a chronic and manageable disease with markedly improved survival. However, prolonged TKI exposure has been associated with rare hematological complications, including secondary lymphoid malignancies.

We describe a 39-year-old woman with CML who developed diffuse large B-cell lymphoma (DLBCL) after long-term nilotinib therapy. She had previously received imatinib and dasatinib, both discontinued due to intolerance and cytogenetic failure. Five years after initiating nilotinib, she presented with gastric pain and right cervical lymphadenopathy. Histopathological examination confirmed a nongerminal center B-cell (non-GCB) subtype DLBCL (CD20+, MUM1+, BCL6+, Ki-67: 80%). The patient received eight cycles of R-CHOP, achieving complete remission. At the most recent follow-up, she maintained a major molecular response for CML and complete remission for lymphoma.

This case highlights a rare occurrence of DLBCL following long-term TKI therapy for CML. Although a direct causal relationship remains unproven, cumulative drug exposure, immune dysregulation, and genomic instability may contribute to lymphomagenesis. Continuous long-term surveillance is essential for early detection and management of secondary malignancies in patients receiving chronic TKI therapy.