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

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 T & uuml;rkiye. 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 T & uuml;rkiye. 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.