Blinatumomab for the Treatment of Philadelphia Chromosome-Negative, Precursor B-cell Acute Lymphoblastic Leukemia.
Blinatumomab is a CD19/CD3 bispescific antibody designed to redirect T cells toward malignant B cells and induce their lysis. It recently gained accelerated approval by the FDA for the treatment of relapsed or refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (RR-ALL). In the phase II trial that served as the basis for approval, blinatumomab demonstrated significant single-agent activity and induced remission [complete remission (CR) and CR with incomplete recovery of peripheral blood counts (CRh)] in 43% of 189 adult patients with RR-ALL; the majority of responders (82%) also attained negative minimal residual disease (MRD(-)) status that did not generally translate into long-term remissions in most cases. Additional studies show that blinatumomab can induce high response rates associated with lasting remissions in patients in first remission treated for MRD positivity, suggesting a role for blinatumomab in the upfront, MRD-positive setting. Blinatumomab infusion follows a predictable immunopharmacologic profile, including early cytokine release that can be associated with a clinical syndrome, T-cell expansion, and B-cell depletion. Neurologic toxicities represent a unique toxicity that shares similarities with adverse effects of other T-cell engaging therapies. Further studies are needed to clarify the optimal disease setting and timing for blinatumomab therapy. Additional insights into the pathogenesis, risk factors, and prevention of neurologic toxicities as well as a better understanding of the clinical consequences and biologic pathways that are associated with drug resistance are needed.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Ofir
O
Wolach
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. rstone@partners.org.
Richard M
RM
Stone
D000818:Animals; D018033:Antibodies, Bispecific / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018941:Antigens, CD19 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000068456:Clinical Studies as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D058990:Molecular Targeted Therapy; D010677:Philadelphia Chromosome; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D016896:Treatment Outcome
D018033:Antibodies, Bispecific; D018941:Antigens, CD19; D000970:Antineoplastic Agents; C510808:blinatumomab