Chronic Myeloid Leukaemia Developing During Long-Term Alectinib Therapy Successfully Managed With Concomitant Nilotinib: A Case Report.

Therapy-related chronic myeloid leukaemia (t-CML) is an extremely rare myeloid neoplasm. Here, we report a first case of CML developing during long-term treatment with alectinib, a highly selective tyrosine kinase inhibitor (TKI) targeting anaplastic lymphoma kinase (ALK). A 53-year-old never-smoking woman with ALK-positive non-small cell lung cancer (NSCLC) developed mediastinal lymph node and brain metastases after curative surgery. Alectinib therapy achieved sustained systemic and intracranial disease control for nearly 3 years without serious adverse events. However, 3 years and 1 month after initiating alectinib, progressive leukocytosis with marked basophilia and circulating immature myeloid cells was observed. Bone marrow analysis confirmed the diagnosis of CML with BCR-ABL1 fusion. Nilotinib was initiated while alectinib was continued, resulting in a rapid hematologic response without serious adverse events. Further accumulation of cases is needed to clarify the potential leukemogenic risk of ALK-TKIs and to establish the safety and clinical utility of combined ALK-TKI and BCR-ABL-TKI therapy.