Introduction
Rapid, iterative improvements in treating B-ALL, especially in younger patients, has been one of the great success stories of cancer therapy. Initial observations that naval personnel exposed to mustard gas during World War II experienced toxic changes in the hematopoietic cells in the bone marrow, creating the fundamental basis of chemotherapy, have given way to the current ability for scientists to identify specific genetic lesions in leukemic blasts for precise targeting of driver kinases. The pace of discovery coupled with clinical relevance has been remarkable1. However, with the exception of tyrosine kinase inhibitors in Philadelphia-chromosome positive B-ALL, other targeted therapies are still in development for B-ALL. The large majority of patients who respond to conventional therapies do well, but the prognosis for patients with relapsed/refractory (r/r) B-ALL remains dismal. Thus, development of new therapies remains vital.
In 2017, the autologous chimeric antigen receptor (CAR) T cell therapy tisagenlecleucel became the first gene therapy and the first genetically engineered adoptive cell therapy to be approved by the Food and Drug Administration (FDA), with an indication for patients up to 25 years old with B-ALL that is refractory or in second or greater relapse2. Shortly after, in May 2018, a second indication for treatment was added, including adult patients with relapsed or refractory large B cell lymphoma after two lines of therapy3. This review will discuss the use of tisagenlecleucel in children and young adults with r/r B-ALL, including its clinical efficacy, common side effects, and current challenges.