TWiPO #12 ~ ALL: Anti-CD19 BiTE and Genetic Risk Groups

August 05, 2011

Host Dr. Tim Cripe and co-host Maureen O’Brien discuss recent papers on immunotherapy and DNA sequencing studies revealing new potential targets in acute lymphoblastic leukemia (ALL).

1:45 min. Results on use of BiTE antibody (Bi-specific T-cell engaging) blinatumomab in adults with lymphoma and leukemia:

Exp Cell Res. 2011 May 15;317(9):1255-60. Epub 2011 Mar 16. Immunomodulatory therapy of cancer with T cell-engaging BiTE antibody blinatumomab

J Clin Oncol. 2011 Jun 20;29(18):2493-8. Epub 2011 May 16. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival.

Use of blinatumomab in pediatrics was recently reported in Germany, and an international phase I/II trial for pediatrics is due to begin accruing this year.

Leukemia. 2011 Jan;25(1):181-4. Epub 2010 Oct 14. Complete remission after blinatumomab-induced donor T-cell activation in three pediatric patients with post-transplant relapsed acute lymphoblastic leukemia.

23:00 min. Recent findings from the TARGET Initiative (Therapeutically Applicable Research to Generate Effective Treatments) http://target.cancer.gov/

Through NIH's TARGET initiative, scientists sequenced 120 candidate genes in 187 high-risk childhood B-precursor acute lymphoblastic leukemias (HR B-ALL) and normal tissues and combined the results with data from previous studies using microarry and gene copy number studies. Sorting through this massive amount of information revealed a high frequency of recurrent genetic alterations in several specific cancer signaling pathways. The information appears to be useful to stratify these patients into subcategories, some of whom do much better than others. These data highlight potential new therapeutic targets in certain subsets of childhood ALL.

Blood. 2010 Dec 2;116(23):4874-84. Epub 2010 Aug 10. Identification of novel cluster groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with gene expression profiling: correlation with genome-wide DNA copy number alterations, clinical characteristics, and outcome

Blood. 2011 Jun 16. [Epub ahead of print] Key pathways are frequently mutated in high risk childhood acute lymphoblastic leukemia: a report from theChildren's Oncology Group

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