Adolescent and Young Adult Hodgkin Lymphoma: Is More Better?

Background: There is a lack of a uniform approach in the treatment of Classical Hodgkin lymphoma (CHL) in adolescents and young adults (AYA). Age cutoffs are arbitrary and based on institutional experience. Chemotherapy using ABVD (Adriamycin Bleomycin Vinblastine Dacarbazine) is the standard of care in most centers for the management of adult CHL. Children and adolescents have been managed with more chemo intense approaches like the EURONET protocol, with better Event-free survival (EFS) outcomes while reducing the need for radiation therapy (RT). There is a knowledge gap regarding the optimum treatment in the AYA group and this pertains to strategies to improve EFS while addressing increasing concerns of acute toxicities and long-term complications of therapy, RT especially. We share the retrospective experience of our center where young adults and adolescents received two different strategies based on an age cutoff alone, resulting in different outcomes.

Methodology: A retrospective chart review of patients aged 10-30 years with newly diagnosed CHL between January 2014 to Dec, 2019 was undertaken. The demographic and clinical profile, treatment details, treatment related complications, RT requirement, and follow-up status for the entire cohort and for each of ABVD and EURONET treatment subsets were analysed. EURONET treatment strategy used 2 cycles of OEPA (Vincristine + Etoposide + Prednisone + Adriamycin) followed by 1-4 cycles of COPDAC (Cyclophosphamide + Vincristine + Dacarbazine + Prednisone), based on the risk level. ABVD protocol used 2 cycles of ABVD followed by 2 - 4 cycles of AVD/ABVD, or intensified chemotherapy based on the interim PET-CT scan response. RT was reserved for inadequate responders during interim assessment in both protocols. Events calculated were death, progression, refractory disease and relapse.

Results: 470 patients with CHL were registered at our centre in the study period. 156 patients were in the 10-30yrs age group. 30 adolescents between ≥10 and <18 years of age (with median age 15.9 years) received the EURONET treatment strategy and 126 patients between ≥18 and ≤30 years (median age 22.7 years) received ABVD protocol. Median follow-up for the entire cohort was 28 months. The patient characteristics are shown in the Table 1. Advanced disease (Stage IIB-IV, and Bulky disease) was seen in 67.4% and 63.3% of patients treated with ABVD and EURONET treatment protocols, respectively. RT was administered in 37.7% of the patients on ABVD and 3.3 % patients on EURONET treatment protocol (Figure 1). 23% of the patients receiving the ABVD therapy had an event compared to 3.3% of the patients in the EURONET treatment group. The EURONET treatment group experienced more grade 3 or 4 acute toxicities (46.6%) when compared to ABVD (8%), the majority being neutropenic fever episodes. There was no treatment related mortality. The 3 year estimated EFS was 93.1% (Std.error=0.04) for the EURONET treated group whereas it was 71.9% (Std.error=0.044) for the ABVD group (Figure 2).

Conclusions: This large single centre retrospective study of CHL in AYA patients shows better EFS and lesser requirement of RT in the EURONET treated group, at the cost of increased acute hematological toxicity. Though an age-matched direct comparison between the treatment groups was not feasible, this study suggests that chemotherapy intensification in the AYA group is possible and may potentially improve EFS while reducing the need for Radiotherapy.