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

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.