B Acute Lymphoblastic Leukemia

P2, N=90, Not yet recruiting, SWOG Cancer Research Network

P1, N=12, Recruiting, University of Michigan Rogel Cancer Center | Not yet recruiting --> Recruiting

P1, N=23, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2026 --> May 2027 | Trial primary completion date: May 2026 --> May 2027

Vignettes explored access to evidence-informed but not universally funded therapies: blinatumomab for low-risk relapse of B-cell acute lymphoblastic leukemia (B-ALL), larotrectinib for TRK-fused soft tissue sarcoma, PBT for unresectable head-and-neck sarcoma, and tisagenlecleucel for first relapse of B-ALL in a patient with Down syndrome. Access to evidence-informed cancer therapies for Canadian children remains variable. Universal funding, simplified approval processes, and the establishment of Canadian PBT centres to reduce travel burden, would ensure timely, equitable access to high-cost therapies.

Following a protocol amendment to evaluate the efficacy of siltuximab as a first-line treatment of CRS, one patient received siltuximab with full resolution of CRS after two doses without needing additional anti-cytokine-directed therapies...This extended experience demonstrates that CD19.22.BBζ CAR T-cell therapy is safe and clinically active, particularly as a bridge to HSCT. Non-response was confined to patients with non-CNS EMD, highlighting the persistent challenge of effectively targeting EMD and informing the design of future CAR constructs.Trial registration numberNCT03448393.

P1, N=24, Suspended, City of Hope Medical Center | Recruiting --> Suspended

P2/3, N=340, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2029 --> Oct 2033 | Trial primary completion date: Feb 2029 --> Oct 2033

P1/2, N=196, Active, not recruiting, The First Affiliated Hospital of Soochow University | Recruiting --> Active, not recruiting

Among the pharmacogenetic factors influencing toxicity of commonly used B-ALL treatments, variants in the TPMT and NUDT15 genes, both involved in the metabolism of 6-mercaptopurine, represent the most robust and clinically validated predictors. Emerging evidence also links additional genetic variants to toxicities associated with other key agents used in ALL treatment regimens, including variants in SLCO1B1 associated with methotrexate-related gastrointestinal toxicity and variants in CEP72 associated with vincristine-induced neuropathy. The integration of pharmacogenomic biomarkers into clinical protocols, enabling genotype-guided dose adjustment, may represent a valuable strategy to avoid toxicity and improve overall cancer outcomes. However, further studies and innovative approaches are required to validate emerging biomarkers and facilitate their translation into routine clinical practice.

RAG-mediated SVs were also associated with relapse risk in T-cell ALL patients. Off-target RAG-mediated SV burden at diagnosis is a risk factor of relapse in pediatric ALL across molecular subtypes and independent of MRD status.

P=N/A, N=107, Not yet recruiting, Gruppo Italiano Malattie EMatologiche dell'Adulto

P2, N=121, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Aug 2025 --> Oct 2027