Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL)

Abstract

BACKGROUND. Elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) have a poor prognosis, with a low complete remission (CR) rate, high induction mortality, and short remission duration. Imatinib (IM) has a favorable toxicity profile but limited antileukemic activity in advanced Ph+ALL. Imatinib in combination with intensive chemotherapy has yielded promising results as front-line therapy, but its value as monotherapy in newly diagnosed Ph+ALL is not known. METHODS. Patients with de novo Ph+ALL were randomly assigned to induction therapy with either imatinib (IndIM) or multiagent, age-adapted chemotherapy (Indchemo). Imatinib was subsequendy coadministered with consolidation chemotherapy. RESULTS. In all, 55 patients (median age, 68 years) were enrolled. The overall CR rate was 96.3% in patients randomly assigned to IndIM and 50% in patients allocated to Indchemo (P = .0001). Nine patients (34.6%) were refractory and 2 patients died during Indchemo; none failed imatinib induction. Severe adverse events were significantly more frequent during Indchemo (90% vs 39%; P = .005). The estimated overall survival (OS) of all patients was 42% ± 8% at 24 months, with no significant difference between the 2 cohorts. Median disease-free survival was significantly longer in the 43% of patients (21 of 49 evaluable) in whom BCR-ABL transcripts became undetectable (18.3 months vs 7.2 months; P = .002). CONCLUSIONS. In elderly patients with de novo Ph+ALL, imatinib induction results in a significantly higher CR rate and lower toxicity than induction chemotherapy. With subsequent combined imatinib and chemotherapy consolidation, this initial benefit does not translate into improved survival compared with chemotherapy induction. © 2007 American Cancer Society.