Treatment Intensification for Childhood B-Cell Lymphoblastic Leukemia With IKZF1 Deletion
In an analysis of Asian trials reported in the Journal of Clinical Oncology, Yeoh et al found evidence that treatment intensification improved outcomes in childhood B-cell acute lymphoblastic leukemia (B-ALL) with IKZF1 deletion (del).
The analysis compared outcomes in the Malaysia-Singapore ALL 2003 (MS2003) and 2010 (MS2010) trials in childhood B-ALL. In MS2003, IKZF1del was not considered in risk assignment, and patients with the alteration received a standard chemotherapy regimen. In MS2010, the presence of IKZF1del was considered to elevate risk; patients with the alteration received chemotherapy intensification, and imatinib was added to the treatment of patients with BCR-ABL1 fusion. The impact of IKZF1del on the 5-year cumulative incidence of relapse was compared between the two studies.
IKZF1del was present in 59 (14.4%) of 410 patients tested in MS2003 and in 50 (18.2%) of 275 in MS2010.
Outcomes With Treatment Intensification
In MS2003, IKZF1del vs wild-type IKZF1 was associated with a significantly higher 5-year cumulative incidence of relapse (30.4% vs 8.1%, P = 8.7 x 10-7), particularly among patients with intermediate risk and no high-risk features (25.0% vs 7.5%, P = .01). IKZF1del was also associated with a higher 5-year cumulative incidence of relapse among patients with BCR-ABL1–negative disease (20.5% vs 8.0%, P = .01). In MS2010, the 5-year cumulative incidence of relapse among patients with IKZF1del decreased to 13.5% (P = .05) and was not significantly different among those with BCR-ABL1–negative disease (11.4% vs 4.4%, P = .09).
Thus, among patients with BCR-ABL1–negative disease, 5-year cumulative incidence of relapse decreased from 20.5% in MS2003 to 11.4% in MS2010. Among the relatively small subgroups of patients with BCR-ABL1–positive disease, the 5-year cumulative incidence of relapse was reduced from 66.7% in MS2003 to 20.0% in MS2010 (P = .06). Overall survival for patients with IKZF1del at 5 years was 69.6% in MS2003 and 91.6% in MS2010 (P = .007).
The investigators concluded, “Intensification of therapy for patients with IKZF1del by upgrading to the next risk group for patients with BCR-ABL1–negative disease and adding imatinib to the treatment of patients with BCR-ABL1–positive disease can negate the adverse outcome of IKZF1del in … contemporary ALL therapy….”
The study was supported by Singapore National Medical Research Council Clinician Scientist Investigator Awards, a Cancer Science Institute, Singapore and Centre grant, Goh Foundation, Children’s Cancer Foundation, Singapore Totalisator Board, and VIVA Foundation of Children With Cancer.
Allen Eng Juh Yeoh, MD, of Viva-University Children’s Cancer Centre, National University of Singapore, is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
