Combination of Olverembatinib and VP Regimen for Newly Diagnosed Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Background Philadelphia Chromosome -positive acute lymphoblastic leukemia (PH+ALL) is a common type of adult ALL, and TKI combined with chemotherapy is the main treatment option; early achievement of molecular remission has been found to be an important factor affecting long-term survival. The combination of third-generation TKI Ponatinib can achieve a higher percentage of early molecular remission and significantly improve the prognosis, but the safety is unsatisfactory; Olverembatinib is a novel third-generation TKI, which has demonstrated better efficacy and safety in patients with CML; This study is intended to explore the efficacy and safety of Olverembatinib in combination with VP regimen in the treatment of newly diagnosed adult PH+ALL.

Methods This is a single-arm, prospective trial that enrolled adult patients with newly diagnosed Ph+ ALL. Patients were treated with a combination of Olverembatinib (40mg QOD d1-28), Vindesine 4mg d1,8,15, Prednisone1mg/Kg/d d1-14, and then gradually tapered off for 28d in induction therapy, Post-induction treatment to be decided by each centre.

Results From February 2022 to December 2023, a total of 26 pts were enrolled and all pts completed induction therapy. Among all , Male 12 and Female 14, the median Age was 52(18-70) years old. Sixteen pts (61.5%) expressed the p190 transcript and ten pts (38.4%) expressed the p210 transcript. IKZF1 mutation detected in 5 patients by second-generation sequencing. All patients achieved CR at the end of induction therapy, and no tumor lysis syndrome or treatment-related deaths occurred. No patients had adverse reactions leading to dose reduction or discontinuation, and no treatment-related non-hematological adverse reactions were observed. Molecular response at the end of induction therapy was MMR in 16 patients (53.8%), CMR in 10 (30.8%). The demand for blood transfusion and the incidence of infections were significantly lower compared with our historical data treating with 2nd generation TKI plus chemotherapy treating with low-intensive chemotherapy plus TKIs. During a median follow-up of 354 days, one patient died of transplant complications, while all the remaining survived without relapse.

Conclusion The combination of Olverembatinib and reduced-intensity chemotherapy (VP) is a safe and effective regimen in patients with newly diagnosed Ph+ ALL. The regimen results in high rates of CMR in the absence of intensive chemotherapy, and promises to improve long-term survival in patients with PH+ALL.