CD antibodies are typically not used in childhood ALL, with the exception of rituximab (Rituxan) which targets the CD20 receptor and is first line therapy for Burkitt lymphoma/leukemia. Alemtuzumab (Campath) targets the CD52 receptors and is used to treat B-cell chronic lymphocytic leukemia. Gemtuzumab ozogamicin (Mylotarg) is an anti-CD33 antibody used to treat childhood AML. Inotuzumab ozogamicin (CMC-544) targets CD22, and was evaluated for the treatment of non-Hodgkin lymphoma and ALL. SGN-CD19A targets CD19, which is currently being evaluated for refractory B-lineage ALL.

Immunotherapy currently has 2 approaches in the treatment of leukemia, both of which utilize autologous T-cell manipulation. Chimeric antigen receptor (CAR) T-cell technology creates autologous T-cells to activate cytotoxic cellular effector mechanisms once human leukocyte antigen (HLA)-independent CD19 antigen-positive ALL cells are detected. Patients with ALL who were relapsed/refractory showed a complete response rate of 90%.  “Smart antibody” technology is another approach. Blinatumomab (Blincyto), which combines single chain antibody fragments of CDC19 and CD3 and brings T-cells closer to a malignant lymphoblastic cell causing lysis, was evaluated in relapsed/refractory B-precursor ALL adult patients. Dendritic cell (DC) vaccinations have shown antileukemic effects against the Wilms tumor gene, and mRNA transfected DC vaccines are being explored as a strategy to delay or prevent AML relapses.


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Radioimmunotherapy, such as ibritumomab tiuxetan (Zevalin) and tositumomab (Bexxar), works to deliver radiation directly to cancer cells. Ibritumomab is indicated for adults with untreated follicular NHL and relapsed/refractory low-grade follicular B-cell NHL refractory to rituximab. Tositumomab is used for relapsed/refractory, low-grade, transformed or follicular NHL expressing the CD20 antigen, and is rituximab refractory.

Small molecules used in the treatment of leukemia include imatinib, dasatinib, and nilotinib, which target the disease-specific BCR/ABL1 rearranged gene products. Potential new small molecules are being developed to prevent the activation of the NOTCH1 mutation, a mutation observed in approximately half of patients with ALL. Other gene mutation targets include Janus kinase (JAK), mammalian target of rapamycin (mTOR), phosphatidylinositol-3-kinase (PI3K) pathways, and signal transducer and activator of transcription (STAT).

As summarized by the reviewers, there are existing modalities as well as novel treatments under development, to improve outcomes and minimize morbidities in ALL and AML.

Reference

<1. >Eryilmaz E, Canpolat C. Novel agents for the treatment of childhood leukemia: an update [published online July 4, 2017]. Onco Targets Ther. doi: 10.2147/OTT.S126368