Evaluation of the Childhood Hodgkin International Prognostic Score (CHIPS) in High-Risk Pediatric Hodgkin Lymphoma Patients Treated on Children's Oncology Group AHOD1331

Background: CHIPS (Childhood Hodgkin International Prognostic Score), a predictive score for event-free-survival (EFS), was originally developed using factors presenting at diagnosis in patients with intermediate-risk Hodgkin lymphoma (HL). Prospective validation of CHIPS in patients was a pre-specified aim of AHOD1331, a trial comparing brentuximab-vedotin, doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide (Bv-AVEPC) to standard ABVE-PC (and response-adapted radiation) in children with high-risk HL. Methods: AHOD1331 was a multicenter randomized phase 3 study. Patients were aged 2–21 years with untreated stages IIB+bulk, IIIB, IV HL. CHIPS was determined by assigning one point each for: Stage IV disease, large mediastinal adenopathy (greater than one-third thoracic diameter), albumin (<3.5 g/dL), and fever (T ≥ 38°C). Associations between CHIPS, baseline patient, and disease characteristics were tested. The validity of CHIPS to predict EFS was evaluated by both overall and within pre-specified subgroups defined by treatment arm, PET2 response, and disease stage. Results: The four CHIPS components were analyzable in 576 of the 587 eligible patients. Distribution of CHIPS did not differ by study treatment arm (p = 0.158). CHIPS was significantly prognostic for EFS in this high-risk cohort (p = 0.008) and was independently predictive of EFS regardless of treatment arm, PET2 response, or stage. In subset analyses, CHIPS remained independently prognostic among patients with PET2 rapid responding lesions (RRL; p = 0.021) or Stage IVB disease (p = 0.047). Conclusion: CHIPS were predictive of EFS in patients with high-risk HL treated on AHOD1331. CHIPS may aid in the allocation of patients to risk-based treatment algorithms, and can serve as an effective, inexpensive, and feasible proxy for more biologically based factors.