ALL-216: Outcomes of Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in Molecular Response at Three Months of Therapy

Abstract

Context The combination of tyrosine kinase inhibitors (TKI) with intensive chemotherapy improves outcome of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-pos ALL), particularly among patients in molecular response within three months of therapy. Objective The aim of this study is to identify prognostic factors for relapse and/or death in patients with Ph-pos ALL after 3 months of therapy. Design Retrospective analysis of patients who enrolled on prospective clinical trials of the combination of hyper-CVAD (HCVAD) with a TKI. Setting MD Anderson Cancer Center. Patients or other participants We analyzed 204 patients with newly diagnosed Ph-pos ALL who were treated with HCVAD with a TKI; imatinib (N=44), dasatinib (N=88), and ponatinib (N=72). Interventions Molecular response was assessed at CR, at 3 months, every 3 months during the first 2 years, and every 3-6 months thereafter. Allogeneic stem cell transplantation was offered at the discretion of patient and treating physician. Ponatinib dose was reduced to 15 mg daily, once CMR is achieved. Main outcome measures Progression -free survival (PFS) was calculated from the date of treatment initiation until date of relapse, or death. Overall survival (OS) was calculated from the time of treatment initiation until death. Results By multivariate analysis for PFS and OS in patients who achieved CMR within 3 months of therapy, ponatinib therapy was the only significant independent factor predicting for progression (P=0.028; hazard ratio [HR], 0.388; 95% confidence interval [CI], 0.166-0.904) and death (P=0.042; HR, 0.379; 95% CI, 0.149-0.966); among patients who did not achieve CMR within 3 months, the achievement of major molecular response was a favorable prognostic factor. Though the number of patients with MMR and without molecular response (i.e., no CMR/MMR) is limited, there was a tendency of improved PFS in patients who received allogeneic stem cell transplant. Conclusions The achievement of CMR within 3 months of therapy is the landmark for long-term survival. Ponatinib maintains CMR, and prevents relapse and death in patients with newly diagnosed Ph-pos ALL. MMR within 3 months was associated with improved survival compared to the lack of MMR within 3 months of TKI therapy.