Philadelphia chromosome-negative acute lymphoblastic leukemia: therapies under development

Abstract

Although the prognosis of adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) has steadily improved over the past decade, less than 50% of patients maintain their remission at 5 years. Several approaches have been explored in the past few years including: monoclonal antibodies - either 'naked' (rituximab) or in combination with an immunotoxin (calicheamicin or maytansin), plant toxin (ricin), or bacterial toxin (Pseudomonas or diphtheria), and a novel bispecific T-cell-engaging antibody (blinatumomab); chimeric antigen therapy using autologous T cells that target CD19-expressing ALL; and novel agents such as proteasome inhibitors, liposomal vincristine, hypomethylating agents, nelarabine and NOTCH1 inhibitors. This review summarizes treatment approaches currently under investigation for the treatment of adult Philadelphia chromosome-negative ALL.

Keywords: NOTCH1 inhibitors; chimeric antigen receptor therapy; immunotoxin; novel monoclonal antibodies; proteasome inhibitors.