Imatinib Gets Nod for Pediatric ALL

Improved treatment strategies for children with acute lymphoblastic leukemia (ALL), the most common pediatric cancer, have led to high survival rates and transformed ALL into a largely curable cancer over the past few decades.

However, a subset of patients with Philadelphia chromosome–positive (Ph⁺) ALL—2% to 3% of children with ALL and 25% of adults—has been an exception, says Kirk Schultz, MD, a senior clinician-scientist at the Child & Family Research Institute and professor at the University of British Columbia in Vancouver, Canada. “They just do not do well,” Schultz says.

In January, the U.S. Food and Drug Administration (FDA) approved imatinib (Gleevec; Novartis) to treat children newly diagnosed with Ph⁺ ALL.

The chromosomal abnormality these children carry is similar to that in chronic myelogenous leukemia (CML), for which imatinib was approved in 2001. In 2011, the FDA approved the tyrosine kinase inhibitor for children with chronic-phase CML, a rare condition.

Schultz led a 2009 study published in the Journal of Clinical Oncology that served as the basis for the Ph⁺–ALL approval and was part of a collaborative effort by the multi-institutional Children's Oncology Group sponsored by the National Cancer Institute.

In the study, children with Ph⁺ ALL who had undergone induction therapy to bring their cancer into remission were treated with intensive chemotherapy alongside daily imatinib.

Schultz says that previous studies suggested imatinib would not be effective as a solo treatment, but the effect of combining it with chemotherapy was dramatic. The team later reported 3-year survival rates of 88% in patients who received continuous doses of the drug. “It's altered the treatment strategy,” he says, with increasing numbers of doctors now choosing this approach over a transplant.

The approval is one of only a few by the FDA for targeted cancer drugs in pediatric use. “Almost everything we use is off label,” Schultz says.

Seeking to improve this situation, the FDA offers incentive programs to encourage drug development for pediatric patients, most recently through the 2012 Safety and Innovation Act. The bill includes a provision under which manufacturers who receive approval for a rare pediatric disease earn a voucher requiring the FDA to review a second drug within 6 months of submission of an application for its approval.