Blinatumomab in de novo AYA ALL—Results of the Australasian Leukaemia and Lymphoma Group ALL09 “SUBLIME” study

Pediatric regimens improve outcomes in adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL) patients. End-consolidation (time point 2 [TP2]) minimal residual disease negativity (MRD^neg) is associated with improved survival. In this study, standard consolidation chemotherapy was replaced with blinatumomab to improve TP2 MRD^neg-a key survival surrogate in B-lineage ALL. From 2019 to 2022, 55 patients constituted the intention-to-treat (ITT) cohort, median age 25 (range, 16-39) years. Using a Simon's 2-stage design, blinatumomab replaced standard consolidation chemotherapy cycles with TP2 MRD^neg as the primary endpoint. Blinatumomab was associated with an improved TP2 MRD^neg rate of 70.8% (95% CI, 55.9%-83.0%) versus the null hypothesis of 60% (P = 0.037). When compared to our previous ALL06 study, median time from protocol I commencement to next treatment phase was 84 versus 97 days (P = 0.0001), with 82.7% versus 45.1% (P < 0.0001), commencing protocol M or high-risk block therapy by day 94. Induction mortality was 1.8%. Blinatumomab was well tolerated. Median follow-up was 42.9 (range, 1.9-54.7) months, with 3-year disease-free survival (DFS) 88.6% (95% CI, 76.3%-94.7%) and 3-year overall survival (OS) 90.5% (95% CI, 78.6%-95.9%) in the ITT cohort. Higher than medium-risk patients had poorer DFS but not OS. Standard genomic risk patients had 100% 3-year DFS and OS. Adverse genomic risk stratified by TP2 MRD^pos predicted poorer DFS but not OS. Blinatumomab consolidation for de novo B-lineage AYA ALL was associated with high MRD^neg rates and excellent survival, particularly in standard-risk disease. Genomics may assist in predicting response to blinatumomab in de novo ALL (ACTRN12618001734257).