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Intensified therapy improves outcomes for childhood B-cell acute lymphoblastic leukemia subgroup
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Intensifying therapy significantly improved OS and reduced the risk for relapse among children with childhood B-cell acute lymphoblastic leukemia and IKZF1 deletion, study data showed.
“ALL is the most common form of childhood cancer. It is a heterogeneous disease driven by various recurrent genetic aberrations, including chromosomal/genetic copy number alterations and translocations that create new fusion transcripts,” Allen Eng Juh Yeoh, MD, associated professor at Yong Loo Lin School of Medicine, National University of Singapore, and colleagues wrote. “These genetic aberrations confer distinctly different treatment outcomes and are incorporated into the 2008 method to determine IKZF1 deletion status, enabling its incorporation into contemporary ALL trials.”
Although IKZF1 deletion increases risk for relapse among childhood B-cell acute lymphoblastic
Leukemia, it had been uncertain whether treatment intensification would improve outcomes.
The researchers performed an analysis of all children with B-ALL in the MS2003 (n = 507; 87.3% of total study population) and MS2010 (n = 316; 91.3% of total study population) studies. Researchers screened all patients for IKZF1 deletion using the multiplex ligation-dependent probe amplication assay. In the MS2010 study, the researchers prospectively upgraded the risk assignment of patients who had IKZF1 deletion to the next highest level and added imatinib to therapy for all children with BCR-ABL1 fusion.
Yeoh and colleagues compared the impact of IKZF1 deletion on the 5-year cumulative incidence of relapse between the two studies.
Patients in both studies had similar characteristics, including regarding the frequency of IKZF1 deletions (MS2003, 14.4% vs. MS2010, 18.2%).
In the MS2003 study — which did not use IKZF1 deletion in risk assignment — patients with IKZF1 deletion had at a significantly higher 5-year cumulative risk for relapse compared with those without the deletion (30.4% vs. 8.1%; P = 8.7 X 10–7). This was particularly true of patients considered intermediate risk who did not demonstrate high-risk features (25.0% vs. 7.5%; P = .01).
IKZF1 deletion also was associated with an increased 5-year cumulative risk for relapse among patients who had BCR-ABL1-negative disease (20.5% vs. 8%; P = .01).
In the MS2010 study, which intensified treatment for patients with IKZF1 deletion, the 5-year cumulative risk for relapse in this group significantly fell to 13.5% (P = .05). Also, 5-year cumulative risk for relapse was no longer significantly different among patients with BCR-ABL1-negative disease and IKZF1 deletion (11.4% v 4.4%).
Among patients with IKZF1 deletions, 5-year OS rose from 69.6% in MS2003 to 91.6% in MS2010 (P = .007).
“We have shown that prospective IKZF1 deletion screening is feasible in a multicenter trial setting,” the researchers wrote. “Intensication of therapy for patients with IKZF1 deletion 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 IKZF1 deletion in a contemporary ALL therapy using the ALL-Berlin-Frankfurt-Munster backbone.” –by Andy Polhamus
Disclosures: Yeoh reports honoraria and consulting and advisory roles from Novartis. No other authors report any relevant financial disclosures.
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