TOPLINE

A pediatric-inspired chemotherapy regimen was associated with a durable survival benefit in adolescents and young adults with Philadelphia chromosome-negative (Ph-negative) acute lymphoblastic leukemia (ALL), according to the 10-year follow-up of the CALGB 10403 study. Late relapses were uncommon, occurring mainly in patients with B-cell ALL. However, less than 40% of patients completed planned therapy because of toxicity or nonadherence.

METHODOLOGY

• Pediatric-inspired regimens have become the standard of care for young adults with ALL. While blinatumomab has recently become a standard consolidation option in patients with Ph-negative B-cell disease, access remains limited, making conventional chemotherapy-only regimens relevant in this population. Initial results from the CALGB 10403 trial established early efficacy, but long-term outcome data remain scarce.
• The prospective phase 2 CALGB 10403 study enrolled 295 adolescent and young adult patients aged 16-39 years (median age, 24 years) with newly diagnosed Ph-negative precursor B-cell or T-cell ALL who received a pediatric-inspired chemotherapy regimen between November 2007 and September 2012.
• The complete response rate after induction was 89%, and induction mortality was 3%. Of the 263 patients who achieved complete response, 28 underwent hematopoietic cell transplantation during first complete response, and an additional 28 underwent transplantation during second complete response or later. 
• The study outcomes included 10-year overall survival, event-free survival, disease-free survival, and time of relapse. The median follow-up duration was 120 months. 
• Researchers evaluated prognostic factors such as obesity (BMI ≥ 30), Ph-like signature, CRLF2 gene expression, and measurable residual disease status after induction in a subset of 80 patients. 

TAKEAWAY

• The 10-year overall survival rate was 56%, the event-free survival rate was 44%, and the disease-free survival rate was 49.3%.
• Among the 102 relapses observed, 18.6% occurred between 3 and 5 years after diagnosis, and 5.9% occurred 5 years after; all late relapses beyond 3 years occurred in patients with B-cell ALL.
• In univariate analysis, obesity, a Ph-like signature, high CRLF2 expression, and detectable measurable residual disease after induction were associated with worse outcomes for overall survival and event-free survival. In multivariable analysis for disease-free survival, obesity (hazard ratio [HR], 1.82) and high CRLF2 expression (HR, 2.84) remained significant risk factors. 
• However, only 39% of patients completed planned therapy due to toxicity or nonadherence. Patients who completed planned maintenance therapy had lower 10-year relapse rates than those who discontinued treatment (21.3% vs 39.6%; P = .01), while patients who discontinued protocol therapy and underwent hematopoietic cell transplantation during first complete response had inferior 10-year disease-free survival than those who did not undergo transplantation (16.7% vs 53.2%). 

IN PRACTICE

“These long-term findings underscore the importance of early risk stratification and will help inform the design of future trials aimed at improving outcomes in [adolescents and young adult] patients with ALL,” the study authors wrote.

“These results should be celebrated, yet it is important to note the limitations,” Jerry W. Luo and Lori S. Muffly, both of Stanford University, California, wrote in an accompanying comment. For instance, “only 39% of patients enrolled on the trial were able to complete all intended therapy.”

SOURCE

This study, led by Wellington F. Silva, University of São Paulo, São Paulo, Brazil, was published online in Blood Advances.

LIMITATIONS

This study was restricted to US centers, which might limit generalizability to resource-constrained settings. Molecular profiling reflected testing available at the time and did not fully characterize all high-risk subgroups by current standards.

DISCLOSURES

This study received funding support from the National Cancer Institute at the National Institutes of Health under multiple award numbers. Silva disclosed receiving research support from Libbs and consulting for Amgen and Servier. Some authors reported receiving research support, playing consulting and advisory roles, and receiving royalties from multiple companies. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.