Among adult patients with BCR–ABL1 negative B-cell acute lymphoblastic leukemia (B-ALL), genomic evaluation may lead to improved risk assessment, according to research published in Blood.
While treatment of BCR–ABL1 negative B-ALL has improved over the past several decades, outcomes in some patient groups remain poor, and poor tolerance of intensive treatment is commonplace. Given the wide use of new markers, such as minimal residual disease, and treatments, including chimeric antigen receptor (CAR) T-cell therapies, the identification of risk categories through genomic research is pressing in this patient population.
Previous research has suggested that particular genetic abnormalities may be linked with differential responses to treatment in BCR–ABL1 negative B-ALL. Using data from the Cancer Research Group E2993 trial (ClinicalTrials.gov Identifier: NCT00002514), researchers aimed to evaluate genomic analysis in conjunction with patient outcomes to determine whether any previously unreported genotypes may affect clinical response and survival.
Overall, data from 1229 patients were included, in which the median age was 30 years (range, 14-65). In this cohort, 93% of patients had a remission, although 41% had a relapse after a median 13 months. The 5-year overall survival (OS) rate was determined to be 42%.
Genomic data evaluable in 264 patients included in this trial were used to categorize patients by risk type. These included standard-risk patients who had favorable outcomes (29.5%), among whom the 5-year OS rate was 65% to 80%. In this group, patients had high-risk genotypes, in which patients had a 5-year OS rate of 0% to 27%, or intermediate-risk genotypes, in which patients had a 5-year OS rate of 33% to 45%.
Genomic markers in the high-risk genotype population included Ph-like (21.2%), KMT2A-AFF1 (12%), low-hypodiploid/near-haploid (14.3%), and BCL2/MYC rearrangement (2.8%).
A total of 40% of patients considered high-risk based on age and white blood cell count had genomic markers linked with standard- and intermediate-risk outcomes.
“These data in a large adult B-ALL cohort treated with a non–risk-adapted approach on a single trial show the prognostic importance of genomic analyses, which may translate into future therapeutic benefits,” the authors wrote.
Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Paietta E, Roberts KG, Wang V, et al. Molecular classification improves risk assessment in adult BCR-ABL1-negative B-ALL. Blood. 2021;138(11):948-958. doi:10.1182/blood.2020010144