IKZF1 Deletion–Based Gene Profile and Outcome in Pediatric B-Cell Precursor ALL
In a study reported in the Journal of Clinical Oncology, Stanulla et al found that a gene profile including somatic deletions in the lymphoid transcription factor–coding gene IKZF1 and deletions in other genes was associated with minimal residual disease (MRD)-dependent very-poor prognosis category in pediatric B-cell precursor acute lymphoblastic leukemia (ALL).
Study Details
The study involved 991 patients with B-cell precursor ALL treated in the Associazione Italiana Ematologia ed Oncologia Pediatrica–Berlin-Frankfurt-Muenster (AIEOP-BFM) ALL 2000 trial with complete information on copy number alterations for IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, Xp22.33/Yp11.31 (PAR1 region; CRLF2, CSF2RA, and IL3RA), and ERG.
IKZFF1plus Profile
IKZF1 deletions that occurred simultaneously with deletions in CDKN2A, CDKN2B, PAX5, or PAR1 in the absence of ERG deletion (IKZF1plus group) were associated with the worst outcome. This group accounted for 6% of B-cell precursor ALL patients and had 5-year event-free survival of 53%, compared with 79% among patients with IKZF1 deletion who did not meet the IKZF1plus definition and 87% among patients without IKZF1 deletion (overall P < .001). The 5-year cumulative relapse incidence in these 3 groups was 44%, 11%, and 10% (overall P ≤ .001). These findings were confirmed in a replication cohort of 417 patients from the trial. Multivariate analysis showed that IKZF1plus was an independent predictor of relapse, with the largest hazard ratio among predictive factors (hazard ratio = 4.00, P < .001).
In analysis stratified for MRD levels after induction treatment, 5-year event-free survival was 94% among MRD standard risk IKZF1plus patients vs 40% among MRD intermediate risk and 30% among MRD high risk IKZF1plus patients (overall P ≤ .001). Rates of 5-year cumulative relapse were 6%, 60%, and 60% in these three groups (overall P ≤ .001).
The investigators concluded, “IKZF1plus describes a new MRD-dependent very-poor prognostic profile in [B-cell precursor ALL]. Because current AIEOP-BFM treatment is largely ineffective for MRD-positive IKZF1plus patients, new experimental treatment approaches will be evaluated in our upcoming trial, AIEOP-BFM ALL 2017.”
The study was supported by ERA-NET TRANSCAN/European Commission under the Seventh Framework Programme, Madeleine-Schickedanz-Kinderkrebsstiftung, Deutsche Krebshilfe, Verein für krebskranke Kinder Hannover eV, Deutsche José Carreras Leukämie-Stiftung, Grant Agency of the Czech Republic, and Austrian Science Fund.
Martin Stanulla, MD, of the Department of Pediatric Hematology and Oncology, Hannover Medical School, 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®.
