Efficacy of Targeted Immunotherapy as Induction or Salvage Therapy in Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis

Abstract

Background: Monoclonal antibodies targeting cluster of differentiation (CD) proteins have been incorporated into standard treatments for multiple types of hematologic malignancies, including acute lymphoblastic leukemia (ALL). This systematic review and meta-analysis investigated the efficacy of using CD-targeted antibodies for ALL. Materials and Methods: The EMBASE and MEDLINE databases were searched for research papers using immunotherapy- and ALL-related terms from inception to July 2021. Eligible studies were randomized, controlled trials (RCTs) or cohort studies in which ALL patients received CD-targeted immunotherapy or conventional chemotherapy as the induction or salvage therapy. The reports had to report our primary outcomes of interest: overall survival (OS), relapse-free survival (RFS), or complete remission (CR), with the patient number for each outcome. The effect estimates with 95% confidence interval (CI) from each study were combined to calculate the pooled-effect estimate, using the Hantel-Maenszel method. Results: Five RCTs and 9 retrospective cohort studies were eligible for the meta-analysis. ALL patients given CD-targeted immunotherapy in the induction or salvage therapy had significantly higher OS and RFS rates than those administered conventional chemotherapy only, with pooled odds ratios (OR) of 2.11 (95% CI, 1.76-2.53; I2, 0%) and 2.25 (95% CI, 1.62-3.14; I2, 61%), respectively. The rates of achieving CR and minimal residual disease negativity were also higher for the immunotherapy group, with pooled ORs of 1.70 (95% CI, 1.07-2.69; I2, 79%) and 2.98 (95% CI, 1.17-7.58; I2, 90%), while developing less risk for febrile neutropenia (pooled OR, 0.22; 95% CI, 0.08-0.58; I2, 84%). Subgroup analyses revealed that all antibody types yielded dramatically better OS rates than those for patients administered chemotherapy alone. Conclusions: The ALL patients receiving CD-targeted immunotherapy as induction or salvage therapy had significantly higher response rates and survival outcomes, as well as lower odds of acquiring febrile neutropenia, than the patients given conventional chemotherapy.