Treatment Intensification for Childhood B-Cell Lymphoblastic Leukemia With IKZF1 Deletion


Key Points

  • Treatment intensification in patients with IKZF1del reduced risk of relapse.
  • Overall survival was improved by treatment intensification for IKZF1del and the addition of imatinib to treatment of BCR-ABL1–positive disease.

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.

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