Session: 612. Acute Lymphoblastic Leukemias: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Diseases, Lymphoid Malignancies
Methods: We retrospectively studied 107 patients with TP53-m ALL treated at seven different academic centers in North America. Genetic profiling of pre-treatment bone marrow samples was performed with a comprehensive panel covering 147 myeloid and lymphoid genes. We also performed RNA-sequencing to identify fusions that define ALL subtypes. Single nucleotide polymorphism (SNP) array was used to define low hypodiploidy.
Results: The median age at diagnosis was 59 years (range, 10-80), 42% were female, 70% White. 89% of pts had B-ALL while 11% had T-lineage ALL. 24% of pts were classified to have therapy-related ALL based on their history of exposure to genotoxic therapy for another cancer. 45% of pts had hypodiploid karyotype, 79% of whom were low-hypodiploid. 7% had hyperdiploid karyotype and 5% had BCR::ABL1. 11 pts had two different TP53 variants. 90% of TP53 variants involved the DNA binding domain. Most frequently observed co-occurring mutations involved CDKN2A (20%), NOTCH1 (12%) and RB1 (10%) genes.
71% of pts were treated with standard cytotoxic chemotherapy, while the remaining pts received newer antibody-based therapies (i.e., inotuzumab, blinatumomab) or venetoclax in first-line setting. 11% of pts received allogeneic hematopoietic cell transplant (HCT) in first complete remission (CR1) while 3% received HCT after relapse (CR2 or CR3). When patients with vs without low hypodiploidy were compared, we did not observe a significant difference in overall survival (OS) as outcomes were poor in both groups (median, 17 vs 19 months, p= 0.89). However, pts who had TP53 AF >0.5 had significantly worse OS when compared to pts with TP53 VAF <0.5 (13 vs 25 months, p= 0.03).
Conclusions: TP53-m ALL is a very high-risk disease subtype and its dismal outcome is independent from presence of co-existing low hypodiploidy. Loss of heterozygosity, characterized by TP53 AF >0.5 is associated with even worse survival. New therapies are urgently needed to improve outcomes in this subset.
Disclosures: Badar: Takeda: Other: advisory board ; Morphosys: Other: Advisory Board; pfizer: Other: Advisory board. Lin: Autolus: Consultancy; Rigel: Consultancy; ADC Therapeutics: Consultancy. Patel: Pfizer: Research Funding; Bristol Myers Squibb: Honoraria; Sobi: Honoraria; AbbVie: Honoraria; Sumitomo: Research Funding; Kronos Bio: Research Funding. Drazer: Argenx: Consultancy. Larson: AbbVie, Amgen, Ariad/Takeda, Astellas, Celgene/BMS, Curis, CVS/Caremark, Epizyme, Immunogen, Jazz Pharmaceuticals, Kling Biotherapeutics, MedPace, MorphoSys, Novartis, and Servier: Honoraria; Astellas, Celgene, Cellectis, Daiichi Sankyo, Forty Seven/Gilead, Novartis, and Rafael Pharmaceuticals: Research Funding; UpToDate: Patents & Royalties: royalties. Odenike: AbbVie; Blueprint Medicines; BMS; Bristol-Myers Squibb/Celgene (Inst); Celgene; CTI; Impact Biomedicines; Kymera; Novartis; SERVIER; Taiho Pharmaceutical; Treadwell Therapeutics: Honoraria; AbbVie (Inst); Agios (Inst); Aprea AB (Inst); Astex Pharmaceuticals (Inst); AstraZeneca (Inst); Bristol-Myers Squibb (Inst); Celgene (Inst); CTI BioPharma Corp (Inst); Daiichi Sankyo (Inst); Incyte (Inst); Janssen Oncology (Inst); Kartos Therapeutics (Ins: Research Funding. Shah: Adaptive Biotechnologies: Consultancy; Amgen: Consultancy; AstraZeneca: Consultancy; Bristol Myers Squibb: Consultancy; Eli Lilly: Consultancy; Jazz Pharmaceuticals: Consultancy; Kite Pharma: Consultancy; Autolus, Beigene, Century Therapeutics, Deciphera, Jazz, Kite/Gilead, Pfizer, Precision Biosciences, Novartis, Takeda: Consultancy; Jazz Pharmaceuticals, Kite-Gilead, Servier: Research Funding; Pepromene Bio: Other: DSMB. Stock: Adaptive: Consultancy, Honoraria; Kura: Research Funding; Kura, Servier, Newave, Adaptive, Jazz, Asofarma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Aldoss: Kite Pharma: Other: consulting fees; Sobi: Other: consulting fees; AbbVie: Other: research support; Takeda Pharmaceuticals: Other: consulting fees; Pfizer: Honoraria, Other: consulting fees; Jazz Pharmaceuticals: Other: consulting fees; Amgen: Honoraria, Other: consulting fees; Syndax Pharmaceuticals, Inc.: Other: consulting fees.
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