# Real-Life Retrospective Turkiye Data of the De-Escalation of ABVD to AVD in Hodgkin Lymphoma: On Behalf of the TSH Turkish Lymphoma Study Group

## TL;DR

This study shows that omitting bleomycin from Hodgkin lymphoma treatment based on PET scans is safe and effective in real-world practice in Türkiye.

## Contribution

The study provides real-world validation of PET-guided de-escalation of ABVD to AVD in Hodgkin lymphoma patients in Türkiye.

## Key findings

- 3-year PFS and OS rates were 86.0% and 96.1%, comparable to the RATHL trial.
- Bleomycin omission after two ABVD cycles was feasible and safe in 73.9% of patients.
- Extranodal involvement and higher IPS were linked to worse outcomes in patients treated with two ABVD cycles.

## Abstract

Background: Classical Hodgkin lymphoma (cHL) demonstrates high survival rates with the ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine); however, the use of bleomycin is associated with a significant risk of pulmonary toxicity. The Risk-Adapted Treatment of HL (RATHL) trial demonstrated that omitting bleomycin in patients with favorable interim Positron Emission Tomography (PET-CT) results did not adversely affect survival outcomes. In this study, we present real-world data from advanced-stage HL patients treated according to the RATHL protocol. Methods: This multicenter, retrospective study included newly diagnosed cHL patients with Ann Arbor stage IIB–IV disease or stage IIA disease with bulky disease or with involvement of three or more sites, enrolled from 29 centers across Türkiye. The analysis focused on patients whose initial treatment was de-escalated from ABVD to AVD (bleomycin was omitted). Data were collected on demographic and clinical prognostic characteristics, interim PET-CT findings (evaluated using the Deauville score), progression-free survival (PFS) and overall survival (OS). Survival outcomes were assessed using Kaplan–Meier analysis. Results: A total of 379 patients were included, with a median age of 34 years (range: 18–78). Following interim PET-CT assessments (After 2 cycles of ABVD), Deauville scores were 1 in 39.8% of patients, 2 in 39.1%, and 3 in 21.1%. Based on these results, bleomycin was omitted immediately after interim PET-CT in 73.9% of patients, after one additional ABVD cycle in 12.1%, and after two additional cycles in 14%. The median follow-up duration was 28 months (range: 6–96). The 3-year PFS and OS rates were 86.0% and 96.1%, respectively. Patients with Deauville scores of 1–2 had a 3-year PFS rate of 87.6%, compared to 79.8% in those with a score of 3 (p = 0.087). Increased age, poor Eastern Cooperative Oncology Group Scale (ECOG) performance status, bulky disease, and higher International Prognostic Scores (IPS) were significantly associated with inferior OS (p < 0.05). There were no significant differences in OS among patients who received 2, 3, or 4 cycles of ABVD. However, among patients treated with 2 cycles of ABVD, both extranodal involvement (p = 0.039) and higher IPS (p = 0.002) were significantly associated with decreased PFS. Conclusions: Our findings demonstrate that PET-guided de-escalation of bleomycin after two cycles of ABVD is feasible, effective, and safe in real-world multicenter practice in Türkiye. The survival outcomes are comparable to those reported in the RATHL study, reinforcing the role of interim PET-CT in guiding individualized therapy. However, patients with high IPS or extranodal involvement may require more tailored management strategies.