Acute lymphoblastic leukemia (ALL) accounts for approximately 20% of adult leukemias, 25% of which are Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). In the past decade, tyrosine kinase inhibitors (TKIs) based regimens greatly improved the prognosis for newly diagnosed and recurrent Ph+ ALL patients, but facing challenges of kinase mutations. In the current study, five relapsed/refractory (R/R) Ph+ ALL patients harboring BCR/ABL kinase mutations were treated with olverembatinib, a third-generation TKI based therapy. Before the treatment, all patients had bone marrow relapses, of whom one presented with central nervous system leukemia (CNSL) and one with both CNSL and extramedullary disease (pleura involvement). The patients received olverembatinib in combination with glucocorticoids or chemotherapy, and intrathecal prophylaxis was used regardless of CNS involvement. At the last follow-up, all patients responded to olverembatinib based treatment with three complete molecular remission (CMR), one complete remission (CR) and one partial remission (PR). Our results suggest that olverembatinib is effective with R/R Ph+ ALL with BCR/ABL kinase mutations and warrants broader clinical evaluation.

No relevant conflicts of interest to declare.

Olverembatinib,an oral, third-generation BCR-ABL1 TKI developed by Ascentage Pharma for the treatment of haematological malignancies, including CML-CP and CML-AP, and solid tumours, such as GIST

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