Role of blinatumomab, inotuzumab, and CAR T-cells: Which to choose and how to sequence for patients with relapsed disease

Abstract

Recent approval of several novel agents has dramatically improved outcomes for patients with relapsed and refractory (R/R) B-cell acute lymphoblastic leukemia. Blinatumomab, a bi-specific T-cell engager targeted to CD3 and CD19, inotuzumab ozogamicin (InO), an antibody-drug conjugate to CD22, and tisagenlecleucel, a CD19 chimeric antigen receptor T-cell with a 4-1BB costimulatory domain, have all demonstrated impressive response rates in R/R B-ALL as compared to historic controls. However, important considerations when choosing among these novel agents include clinical features that may impact efficacy, such as relative disease burden, antigen expression, and T-cell function, as well as patient and disease characteristics that may contribute to risk of toxicity. In addition, suitability of the patient for hematopoietic stem cell transplant (HSCT) as well as patient preference must also be considered. This review will focus on factors to weigh when choosing an agent in the setting of R/R disease and important challenges moving forward.

Keywords: Acute lymphoblastic leukemia; immunotherapy.