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.