Philadelphia Chromosome as a Clinically Favorable Prognostic Factor of B-cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma in Transplant-Ineligible Elderly Patients in the Era of Molecular-Targeted Therapy

Background and objective There is scarce data on the treatment outcomes of B-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL) in elderly patients in the era of tyrosine kinase inhibitors (TKIs), blinatumomab, and inotuzumab ozogamicin. In light of this, we aimed to address this gap in data by conducting this retrospective study. Methods Treatment outcomes were retrospectively evaluated by using data from transplant-ineligible patients aged 65 years or older with newly diagnosed B-ALL/LBL (n=29) at two hospitals in Oita, Japan between 2013 and 2023. Results The median age of the cohort was 72 (65-88) years, and 10 patients were male; 17 patients had Philadelphia chromosome (Ph)-positive ALL, and the others had Ph-negative ALL. Dasatinib combined with prednisolone was the most common induction therapy for Ph-positive ALL (88.2%). Complete response (CR) was achieved in 93.1%, and the CR rate did not differ significantly between Ph-positive ALL (100%) and Ph-negative ALL (83.3%) (p=0.16). The median observation period was 1.52 (range: 0.03-8.98) years. Overall survival (OS) and event-free survival (EFS) were significantly longer in Ph-positive ALL patients than in Ph-negative ALL patients on univariate analysis (OS: p=0.011, EFS: p=0.041). Multivariate analyses showed that the presence of Ph was significantly and independently associated with longer OS [hazard ratio (HR): 0.29, 95% confidence interval (CI): 0.10-0.87, p=0.027] and EFS (HR: 0.34, 95% CI: 0.12-0.91, p=0.03). There was no difference in relapse-free survival (RFS); 13 patients (76.5%) with Ph-positive ALL were treated with ponatinib (salvage therapy, n=7; consolidation or maintenance therapy in CR, n=6). Six of seven patients (85.7%) with ponatinib salvage therapy achieved CR, and all six patients treated with ponatinib consolidation or maintenance therapy retained CR at the last follow-up. Six patients (Ph-positive ALL: n=4; Ph-negative ALL: n=2) were treated with blinatumomab, including salvage therapy for primary refractory or relapse (n=3), and consolidation therapy due to intolerance to conventional chemotherapies (n=3). Two of three patients with blinatumomab salvage therapy achieved CR, and all three patients with blinatumomab consolidation therapy maintained CR in follow-up. Two patients (Ph-positive ALL: n=1; Ph-negative ALL: n=1) were treated with inotuzumab ozogamicin for relapsed or refractory ALL. A patient with Ph-positive ALL for the third relapse achieved CR, which was sustained for three years. The other patient with Ph-negative ALL for primary refractory achieved CR but relapsed after the fourth course of inotuzumab ozogamicin. Conclusions Elderly patients with Ph-positive ALL showed significantly longer OS and EFS than those with Ph-negative ALL in the era of molecular-targeted therapy.