A case study suggests that the third-generation tyrosine kinase inhibitor (TKI) bosutinib may be considered as induction therapy for blast phase chronic myeloid leukaemia (CML) in older patients.
The study also raises the possibility that bosutinib may have efficacy for the treatment of central nervous system (CNS) involvement, the researchers say.
As described in Case Reports in Hematology, the patient had initially presented with chronic phase CML at the age of 72 years and been treated sequentially with the TKIs imatinib, dasatinib and then nilotinib.
The patient achieved a complete cytogenetic response and major molecular response with dasatinib and then, after recurrence, with nilotinib.
After 7 years, however, the patient underwent further investigation for fatigue and weight loss and a poor performance status. Bone marrow biopsy revealed 42% blasts with partially positive status for CD34, indicating B cell lymphoblastic leukaemia infiltration.
The patient was treated with prednisone and bosutinib 500 mg/day, as well as CNS prophylaxis, consisting of methotrexate and dexamethasone.
Although the patient was hospitalised with pancytopenia – considered to be a side effect of bosutinib – and pneumonia, bone marrow biopsy indicated the acute lymphoblastic leukaemia was in remission.
After a 2-week interval, bosutinib was resumed at the lower dose of 500 mg every 2 days.
The patient underwent cranial imaging after developing depression and lack of appetite and this showed cerebral and cerebellar atrophy with CNS involvement; the patient was treated with radiotherapy, methotrexate and intrathecal chemotherapy but was unable to tolerate methotrexate–vincristine maintenance treatment.
Nevertheless, the patient continued with the bosutinib regimen and, after 14 months, achieved a complete haematological response and remission.
“Although there are no reports that have demonstrated bosutinib’s efficacy in CNS involvement, we continued with the treatment after the suspected CNS involvement was determined because he had been unresponsive to other TKIs”, explain Erden Atilla, from Ankara University School of Medicine in Turkey, and co-authors.
They therefore conclude: “Bosutinib, as a third-generation TKI, can be an alternative agent in elderly blastic-phase CML patients with a high tolerability profile and increased survival. “If bosutinib is found to be effective in CNS involvement, it should be investigated further.”
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