Induction failure (IF) as a prognostic marker in adult acute lymphoblastic leukemia (ALL).

Abstract

6546 Background: Despite advances in the treatment of adult ALL, risk factors for IF and optimal management are poorly understood. We aimed to characterize patients (pts) with IF after therapy for newly diagnosed (nd)ALL and their outcomes. Methods: We performed a retrospective chart review of adult ndALL pts treated at Weill Cornell Medicine from 2012-2025. We defined IF as failure to achieve < 5% bone marrow blasts, count recovery and extramedullary disease clearance after 1 cycle of induction. Fisher’s exact test was used for analysis of discrete variables and Wilcoxon rank-sum test for continuous ones. Results: Among 220 pts, 48.2% were female, mean age at diagnosis was 50.5 (18-87) yrs, 74.5% had B-cell ALL (of which 41.5% Ph+), with median follow-up 24.5 months. 34 pts (15.5%) had IF (22 B cell, 12 T cell). B-cell IF patients were more likely to have Ph-(77.3% vs 50%, p=0.0211) or Ph-like phenotype (13.6% vs 3.5%, p=0.0753). IF pts were more likely to have CNS disease at diagnosis (p= 0.034). There was no significant difference in baseline median white cell count (13.18 vs 9.60 p=0.4) or LDH (448 vs 517 p=0.17) in IF vs non-IF pts. IF was not associated with age, asparaginase-treatment, BMI, abnormal cytogenetics, pertinent mutations, or year of diagnosis. On multivariable logistic analysis controlling for age and lineage, CNS disease at diagnosis remained associated with IF (OR 2.81, p=0.0343). Overall survival (OS) was significantly worse in IF vs non-IF pts at 3-years (29.2% vs 66.8%, p = 0.0002). OS did not vary by CNS disease at diagnosis in IF pts. Of IF pts, 27/34 (79.4%) achieved CR with subsequent therapy (median time to CR 68.5 days, range 21-228), with improved survival vs the 7 pts (5 B cell, 2 T cell) who did not (p = 0.00001). 4/7 patients without CR died within 4 months, and none of these 7 patients received allo-SCT. In the 27 IF pts attaining later CR, there was a trend towards worse OS vs non-IF pts (1029 days vs not reached, p=0.0659), though importantly a subset of 10 pts who achieved minimal residual disease (MRD)-negativity had OS similar to the non-IF group (p=0.95). IF patients were more likely to receive allo-SCT than non-IF patients (51.4% vs 29.7%, p=0.0164). Receiving allo-SCT tended to be associated with improved survival in this group (p=0.0578) vs no allo-SCT. 16/22 B cell IF patients received blinatumomab and/or inotuzumab. These were not associated with MRD-negative status or allo-SCT, but did show a trend towards subsequent CR (p=0.1) and better OS (p=0.1119). Conclusions: In our single-center retrospective cohort of ALL pts, 15.5% had IF. 29.4% of these patients (4.5% of the total cohort) were able to achieve MRD- status with subsequent treatment, resulting in outcomes comparable to pts without IF. ALL-IF patients should be closely monitored for MRD and may benefit from early application of immunotherapeutic approaches and/or allo-SCT.