Unfavorable Prognosis in Childhood T-Cell ALL Persists Despite Advancements in Treatment

By Cailin Conner - September 20, 2023

According to a study published in the Journal of Clinical Oncology, despite advancements in therapy, the prognosis for induction failure (IF) in childhood T-cell acute lymphoblastic leukemia (ALL) remains poor. “The lack of a unifying genetic driver suggests alternative approaches, particularly using immunotherapy, are urgently needed,” the investigators wrote.

With the goal of addressing the limited understanding of clinical and genetic factors that influence outcome in a cohort of patients with T-cell ALL IF, investigators examined all cases of T-cell ALL IF in 2 randomized trials (UKALL2003 and UKALL2011) to identify risk factors, treatments, and outcomes.

The results of the study revealed that IF occurred in 10.3% of T-cell ALL cases. Additionally, IF occurred in 20% of patients with T-cell ALL aged >16 years, suggesting that age may play a role in treatment resistance.

Despite the increased utilization of nelarabine-based chemotherapy followed by hematopoietic stem cell transplantation in the randomized UKALL2011 trial, there was no observable enhancement in the overall treatment outcome. The presence of persistent molecular residual disease at the end of consolidation treatment was linked to a notably worse prognosis (5-year overall survival [OS] rate, 14.3% vs 68.5%; hazard ratio [HR], 4.10; 95% CI, 1.35-12.45; P=.0071).

Genomic profiling showed 25 distinct initiating anomalies, which converged on 10 subtype-defining genes. Notably, an abundance of TAL1 noncoding anomalies was identified, and these anomalies were associated with an unfavorable prognosis (5-year OS rate, 12.5%). When TAL1 anomalies were combined with mutations in the MYC and RAS pathways, a genetic stratification emerged that could effectively identify patients highly likely to experience treatment failure (5-year OS rate, 23.1% vs 86.4%; HR, 6.84; 95% CI, 2.78-16.78; P<.0001).

“The abysmal outcome in those relapsing after IF emphasizes that there is only 1 opportunity to cure these patients and better therapies are urgently needed to achieve this. The lack of progress made in relapsed [or] refractory [T-cell ALL] over the past 2 decades contrasts starkly with the influx of efficacious immunotherapies in [B-cell ALL],” the investigators wrote. “Thankfully, similar agents are now on the horizon for [T-cell ALL] with monoclonal antibodies and CAR T cells entering the clinical arena.”

Source: Journal of Clinical Oncology

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