Is It Better to Start Treatment with ABVD and Continue with PET2-Adapted Approach or Should We Use 2 Cycles of Beacopp Escalated and 2 Cycles of ABVD and Irradiation in Early Unfavorable Hodgkin Lymphoma?
Authors: Mocikova Heidi , Markova Jana , Gaherova Lubica , Maco Maria , Sykorova Alice , Belada David , Lukasova Marie , Prochazka Vit K , Hradska Katarina , Ďuraš Juraj , Havranek Ondrej , Kozak Tomas 
Published: November 2021

Abstract
Introduction. EORTC H10 trial confirmed better selection of patients who needed reduced or more intensive treatment using PET response after 2 cycles of ABVD in early stages of classical Hodgkin lymphoma (cHL). GHSG HD17 showed that radiotherapy can be safely omitted in PET4-negative early unfavorable HL treated with 2 cycles of BEACOPP escalated plus 2 cycles of ABVD (2+2 chemotherapy). We compared PET2-adapted approach including 30Gy involved-node radiotherapy (INRT) with 2+2 chemotherapy followed by 30 Gy INRT (or involved-field radiotherapy, IFRT) regardless of interim PET in patients with early unfavorable cHL assessed according to the GHSG risk factors.
Methods. Overall 243 patients with early unfavorable cHL (aged 18-60 years) prospectively observed in the Czech Hodgkin lymphoma study group registry between 2003-2020 were analyzed. Patients in clinical stage IIB with massive mediastinal tumor and/or with extranodal disease were not included into this analysis as they were treated with BEACOPP escalated only. Chemotherapy 2+2+30 Gy INRT/IFRT received 213 patients. Overall 30 patients were treated with PET2-adapted approach: 29 PET2-negative patients received 4 cycles of ABVD and 30 Gy INRT and one PET2-positive patient was treated with 2 cycles of ABVD plus 2 cycles of BEACOPP escalated and 30 Gy INRT.
Results. Median age at the time of cHL diagnosis was 32 (range 18-59) years. Median follow-up was longer in the 2+2+INRT/IFRT group (91.3, range 6.2-211.2) months when compared to the PET2-adapted approach (19.4, range 6.4-90.4) months. The estimated 2-year progression-free survival (PFS) did not differ in both groups (100% [95% CI 100-100] both), however, the estimated 5-year PFS was significantly better in the 2+2+INRT/IFRT group (99.5% [95% CI 98.5-100]) in comparison to PET2-adapted treatment (75.0% [95% CI 32.5-100]), p&lt;0.001. The estimated 5-year overall survival was comparable in both groups (2+2+INRT/IFRT: 99.5% [95% CI 98.5-100]; PET2-guided treatment: 100% [95% CI 100-100]). Hematological toxicity was reported in most of the patients in both groups. Grade 3 non-hematological toxicity occured in 3 patients in the 2+2+INRT/IFRT approach (2 infections, 1 deep vein thrombosis).
Conclusion. This retrospective analysis indicates that 2+2+INRT/IFRT is more effective in the long-term disease control, but there is no difference in overall survival in both groups. The current approach includes 2+2 chemotherapy and INRT is added in PET4-positive patients.
This work was supported by the Research project Q 28 Progres awarded by the Third Faculty of Medicine of Charles University in Prague in the Czech Republic.

Disclosures
Belada: Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Celgene: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding.