Pediatric imatinib for Philadelphia-chromosome ALL fights relapse

Aug 15 2012

By Lynda Williams, Senior MedWire Reporter

Trial findings confirm the benefits of imatinib therapy in children with Philadelphia-chromosome-positive acute lymphoblastic leukemia (ALL).

The European intergroup study of postinduction treatment of Philadelphia-chromosome-positive ALL (EsPhALL) results for the receptor tyrosine kinase inhibitor add to those of the Children's Oncology Group (COG) study, which showed improved disease-free survival (DFS) with the treatment compared with historical controls.

In the current study, published in The Lancet Oncology, children with a good risk, defined as an early response to induction treatment and complete remission, who were given postinduction imatinib 300 mg/m² per day (n=46) plus chemotherapy modeled on a Berlin-Frankfurt-Munster high-risk backbone had significantly greater 4-year DFS than their counterparts given chemotherapy alone (n=44), at 72.9% and 61.7%, respectively.

This gave an intention to treat hazard ratio for failure of 0.63, after adjusting for minimal residual disease, report Andrea Biondi (University of Milano-Bicocca, Monza, Italy) and co-authors.

For the 70 poor-risk patients, all of whom were given postinduction imatinib therapy, the 4-year survival rate was 53.5%, and therefore significantly different from that achieved by good-risk patients. This result contrasts with that of COG study, which found that minimal disease after induction did not significantly predict DFS, the authors note.

"In view of the different induction protocols used in each study, interpretation of this variation is difficult," the researchers say.

Biondi et al suggest that patients with a poor response to chemotherapy including prednisone may comprise those with the most highly resistant disease. "Whether starting imatinib (or a second generation tyrosine-kinase inhibitor) during induction would cancel the negative effect of poor early response with steroids is still unclear," they write.

There was no significant difference in the rate of serious adverse events between good-risk patients treated with and without imatinib, and poor risk patients (28, 32, and 34%, respectively), with infection the most common events.

"Our data support further investigation of new tyrosine-kinase inhibitors in conjunction with the established chemotherapy backbone for treatment of children with Philadelphia-chromosome-positive ALL," the team concludes.

"The EsPhALL network is assessing the effect of earlier, continuous, and longer exposure to imatinib and use of a second generation tyrosine-kinase inhibitor. Possible next steps are assessments of whether exposure to tyrosine-kinase inhibitors can change the intensity of chemotherapy and the use of transplantation in first remission."

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