Session: 613. Acute Lymphoblastic Leukemias: Therapies Excluding Allogeneic Transplantation: Poster II
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Pediatric, Diseases, Therapy sequence, Treatment Considerations, Young adult , Lymphoid Malignancies, Human, Study Population
The primary objective was to compare disease-free (DFS) and overall survival (OS) in patients receiving identical systemic COG ALL therapy ±IM2. Secondary objectives were to examine the efficacy of IM2 in SR-ALL with the current standard q12week steroid/vincristine pulses and within cytogenetic subsets. Eligibility criteria for these analyses were designed to match treatment arms between trials. For HR-ALL, inclusion criteria were age ≥13 years old and end of induction (EOI) minimal residual disease (MRD) <0.01%, based on eligibility for the AALL1131 VHR arm. For SR-ALL, patients with neutral or favorable cytogenetics (ETV6::RUNX1 or double trisomies 4 and 10) and EOI MRD <0.01% were included. Patients with BCR::ABL1, KMT2A rearrangement, hypodiploidy, or EOI MRD ≥0.01% were excluded due to treatment variation among trials. Statistical analyses compared DFS and OS via log-rank test and were reported at five years with standard errors. Cox multivariable models analyzed hazard ratios (HR) adjusted for presenting features (demographics, white blood cell count, cytogenetics, central nervous system status).
In HR-ALL, 249 patients from AALL0232 and 65 patients from AALL1131 VHR were eligible. For AALL1131 VHR versus AALL0232, the addition of IM2 was not associated with a difference in DFS (85%±4.7 vs 85%±2.5, p=0.91) or OS (90%±4.0 vs 90%±2.1, p=0.63). In SR-ALL patients receiving q4week pulses in Maintenance, 1,317 patients were eligible from AALL0331 and 1,186 patients from AALL0932. As compared to AALL0331, addition of IM2 in AALL0932 was associated with significantly higher DFS (94%±0.7 vs 91%±0.8, p= 0.0024) and OS (99%±0.4 vs 97%±0.5, p<0.0001). In the Cox multivariable model comparing SR-ALL patients receiving q4week pulses, IM2 significantly decreased risk for an event (HR 0.67, p=0.0048). In SR-ALL patients enrolled in AALL0932 who were randomized to receive q12week pulses (n=1,178), addition of IM2 was associated with higher DFS and OS versus AALL0331 (95%±0.7 vs 91%±0.8, p<0.0001 and 99%±0.3 vs 97%±0.5, p<0.0001, respectively). However, adjusted Cox models demonstrated the decreased event risk was largely in those with neutral cytogenetics (HR=0.62, p=0.0179), with OS (HR=0.58, p=0.0783). No difference in DFS/OS was noted in SR-ALL with favorable cytogenetics.
Within the limitations of unplanned subset analyses, we determined that IM2 may be able to be safely omitted in MRD-negative patients with HR-ALL or with SR-ALL with favorable cytogenetics and that IM2 may provide a survival advantage for patients with SR-ALL, neutral cytogenetics, and MRD <0.01%. Whether IM2 is necessary in patients with higher risk B-ALL due to adverse cytogenetics or persistent MRD was not addressed in these analyses.
Disclosures: Orgel: Jazz Pharma: Consultancy. Wood: Cellnomics LLC: Current equity holder in private company; Amgen: Consultancy. Angiolillo: Servier Pharmaceuticals: Current Employment. Teachey: Jazz: Membership on an entity's Board of Directors or advisory committees; NeoImmune Tech: Research Funding; BEAM Therapeutics: Research Funding. Carroll: Merck: Consultancy. Hunger: Amgen: Current equity holder in publicly-traded company, Honoraria; Jazz Pharmaceuticals: Honoraria; Servier US: Honoraria; Novartis: Consultancy.