Toxicity and Tolerability of the OEPA/COPDAC Regimen in Children and Adolescents With Hodgkin Lymphoma: A Real-World Experience

Abstract

Vincristine, etoposide, prednisone, and doxorubicin (OEPA)/cyclophosphamide, vincristine, prednisone, and dacarbazine (COPDAC) regimen represents a preferred chemotherapy backbone for response-adapted treatment of pediatric Hodgkin Lymphoma (HL). Epidemiological, demographic, and clinical characteristics differ between children with HL from developing and developed countries. Administration of OEPA/COPDAC in low-middle-income countries (LMIC) has been associated with high treatment-related mortality (TRM), hindering its wide adoption. In this comprehensive analysis, we evaluated OEPA/COPDAC-associated adverse events and their impact on treatment delivery in 301 Egyptian patients with pediatric HL aged 2.5–17.9 years. The mean age at presentation was 10.1 years (72% of patients ≤ 13 years) with a male-to-female ratio of 2.6:1. The three treatment groups (TG) were represented. Nodular Sclerosis classic HL (59.8%) represented the most common histopathological subtype. Adverse events were reported during 49.8% of the administered cycles. Eighty-nine and 76.4% of the patients encountered toxicity during OEPA1 and OEPA2 cycles respectively. The frequency of toxicity during COPDAC cycles ranged from 16% to 29.4%. Grade 3/4 decreased neutrophils were the most commonly occurring AE during OEPA cycles (range 71%–85%). Profound neutropenia occurred in 27.9% and 13.8% during OEPA1 and OEPA2 respectively. Profound neutropenia significantly differed across age groups. Treatment-related mortality (TRM) occurred in 1% of the patients. Ninety-eight percent of the scheduled chemotherapy cycles were successfully administered. Treatment modification due to toxicity was required in 9.3% of patients whereas 121 hospital admissions (891 days) were reported. Recurrent toxicity that is, toxicity in > 50% of administered cycles and consequently hospital admission significantly differed across age groups. Our findings support that low TRM is achievable in LMIC centers with adequate infrastructure and treatment capabilities. We additionally provide real-life data on the associated treatment modification and hospital admission.