Outcomes of Tyrosine Kinase Inhibitors Maintenance Therapy with or without Allogeneic Hematopoietic Stem Cell Transplantation in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia in First Complete Remission: A Systematic Review and Meta-Analysis

Abstract

We conducted a systematic review and meta-analysis to compare outcomes of tyrosine kinase inhibitor (TKI) maintenance therapy with or without allogeneic hematopoietic stem cell transplantation (HSCT) in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in first remission (CR1). A literature search was performed on PubMed, Cochrane, and Clinical trials.gov. After screening 1720 articles, 12 studies were included. Proportions and odds ratios (OR) with 95% confidence intervals (CI) were computed. I² provides an estimate of the percentage of variability in results across studies that is due to real differences and not due to chance. Of 1039 patients, 635 (61%) had TKI alone and 404 (39%) patients had HSCT followed by TKI. At 3 years, a trend towards poor overall survival (OS; OR 0.67, 95% CI 0.39-1.15, I² = 68%), (disease-free survival; OR 0.58, 95% CI 0.26-1.29, I² = 76%), and higher relapse rate (RR; OR = 2.52, 95% CI = 1.66-3.83, I² = 26%) was seen with TKI alone compared to HSCT-TKI. Although HSCT followed by TKI maintenance in Ph+ ALL has long been considered standard of care, the introduction of potent third-generation TKIs and bispecific T-cell engagers such as Blinatumomab has significantly improved outcomes while sparing the need for HSCT in newly diagnosed patients.

Keywords: Allogeneic hematopoietic cell transplantation; Cellular therapies; Hematologic malignancies; Outcomes; Philadelphia positive acute lymphoblastic leukemia; Protein kinase inhibitors.