Olverembatinib Plus Low-Intensive Regimen in Frontline Therapy for Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia： a Case Series from a Single Center

BCR::ABL1 tyrosine kinase inhibitors (TKI) have shown promising results in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). However, resistance and intolerance to TKIs remains a clinical challenge. Olverembatinib is an oral, novel third-generation TKI developed by Ascentage Pharma. Olverembatinib is effective against most ABL1 kinase domain mutants, including mutant T315I. In November 2021, olverembatinib was approved in China for the treatment of adults with BCR::ABL1T315I-mutant chronic myeloid leukemia (CML). However, data on clinical use of olverembatinib in Ph+ ALL are very limited. Herein, we report a retrospective analysis of patients with newly diagnosed Ph+ ALL who received olverembatinib plus low-intensive regimen (VP: Vindesine + dexamethasone / prednisone ) at our institution. Olverembatinib was administered at a dose of 40 mg orally QOD continuously. Vindesine was given 4 mg intravenously on day 1, 8, 15, 22 and dexamethasone /prednisone was administered from days 1 to 22 during induction. After two courses of olverembatinib plus VP, olverembatinib-based regimens was recommended for consolidation. The choice of sequentially consolidation treatment with allogeneic hematopoietic stem-cell transplantation (allo-HSCT), blinatumomab or intensive chemotherapy, was made by the investigators and patients preference. Prophylactic intrathecal chemotherapy with cytarabine and dexamethasone was administered in each cycle. Maintenance therapy was olverembatinib and low-intensive regimens. The primary endpoint was complete molecular response (CMR) rate. CMR was defined as BCR-ABL1/ABL1 ratio < 0.01% by quantitative real-time polymerase chain reaction(qPCR). Between November 2021 and June 2022, a total of 12 consecutive patients with Ph +ALL treated with the olverembatinib plus VP at our center were enrolled. The median age was 48 years (range, 18-72 years). Ten patients were male and two were female. The median white-cell counts were 77,000 per cubic millimeter (range, 1200 to 356,000). Seven patients had the p190 fusion transcript, five had the p210 transcript. All 12 patients completed induction phase with olverembatinib plus VP regimen. At the end of the 4 weeks of induction , all 12 patients (100%) achieved complete hematologic response. The primary endpoint CMR was reached in 6/12 patients (60%) at 4 weeks; in 12/12 patients (100%) at 8 weeks. For treatment-emergent adverse events, most of which were mild and manageable. No serious nonhematologic toxicities were observed. With a median follow-up of 5 months, all patients were in CMR in the last follow-up, four patients proceeded to allo-HSCT. Conclusions: Olverembatinib was well tolerated and showed high early response in newly diagnosed Ph +ALL. These promising findings warrant further investigation in future trials.