Session: 613. Acute Lymphoblastic Leukemias: Therapies Excluding Allogeneic Transplantation: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research, Pediatric, Study Population, Human
Methods: Event free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were compared among CNS2 pre- vs post-amendment patients, stratified by NCI risk group. Multivariable models were also constructed to adjust for demographic and disease variables.
Results: When stratified by trial, pre- and post-amendment patients did not differ significantly by demographic or disease factors, including age at diagnosis, end of induction bone marrow MRD status, and blast cytogenetics.
For patients with NCI SR B-ALL and CNS2 enrolled on AALL0932 (8% of study population, n=535 pre-amendment, n=207 post-amendment), the 5-year EFS pre- vs post-amendment was 86.7% (SE, 1.5%) vs 88.9% (SE, 2.3%), p=0.44, and 5-year OS pre- vs post-amendment was 95.5% (SE, 0.9%) vs 96.0% (SE, 1.5%), p=0.50. The 5-year CIR for isolated CNS relapse was 3.6% (SE, 0.8%) vs 4.0% (SE, 1.4%) pre- vs post-amendment, p=0.71, and for combined marrow and CNS relapses was 1.0% (SE, 0.4%) vs 1.0% (SE, 0.7%), p=0.71. Among post-amendment NCI SR patients (CNS1 n=2033, CNS2 n=207), the adverse impact of CNS2 status remained statistically significant, with 5-year EFS of 93.2% (SE, 0.6%) vs 88.9% (SE, 2.3%) for CNS1 vs CNS2, p=0.025.
For patients with NCI HR B-ALL and CNS2 status (16.6% of study population, n=488 pre-amendment, n=313 post-amendment), the 5-year EFS pre- vs post-amendment was 66.5% (SE, 2.4%) vs 73.5% (SE, 3.4%), p=0.095 and OS pre- vs post-amendment was 80.2% (SE, 2.0%) vs 84.0% (SE, 2.8%), p=0.20. The 5-year CIR for isolated CNS relapse was 5.9% (SE, 1.1%) vs 5.6% (SE, 1.4%) pre- vs post-amendment, p=0.92, and for combined marrow and CNS relapses was 2.7% (SE, 0.8%) vs 0.7% (SE, 0.5%) pre- vs post-amendment, p=0.068. The post-amendment impact of CNS status on outcomes remained significant for NCI HR patients (CNS1 n=1326, CNS2 n=313), with 5-year EFS of 78.4% (SE 1.5%) vs 73.5% for CNS1 vs CNS2, p=0.049.
In multivariable analyses conducted separately for AALL0932 and AALL1131 and adjusting for disease prognosticators and race/ethnicity, treatment post-amendment was not significantly associated with any difference in EFS (AALL0932: hazard ratio 0.99, 95CI 0.6-1.6, p=0.95; AALL1131: hazard ratio 0.80, 95CI 0.6-1.1, p=0.14). Additional analyses evaluating subgroups defined by cytogenetics (favorable, neutral, unfavorable) or disease response did not find any subpopulation that significantly benefited from extra IT chemotherapy. The additional therapy was not associated with an increase in toxicity.
Conclusions: Additional IT cytarabine during induction for patients with CNS2 disease on AALL0932 and AALL1131 did not improve outcomes or mitigate the adverse prognostic impact of CNS2 status. Rates of CNS2 status and impact on outcome vary greatly between cooperative groups, and factors such as variability in CSF analysis and post-induction therapy need to be considered in order to identify this population accurately and treat accordingly. Given these results showing lack of improvements in outcome and concerns surrounding repeated anesthesia exposure, future frontline B-ALL COG studies will not include additional IT cytarabine for the CNS2 population. Alternative methods of improving outcomes for CNS2 patients are needed.
Disclosures: Angiolillo: Servier Pharmaceuticals: Current Employment. Hunger: Jazz Pharmaceuticals: Honoraria; Servier US: Honoraria; Amgen: Current equity holder in publicly-traded company, Honoraria; Novartis: Consultancy. Teachey: Jazz: Membership on an entity's Board of Directors or advisory committees; NeoImmune Tech: Research Funding; BEAM Therapeutics: Research Funding. Gupta: Amgen: Other: Educational session.