Advanced Hodgkin lymphoma in the East of England: a 10-year comparative analysis of outcomes for real-world patients treated with ABVD or escalated-BEACOPP, aged less than 60 years, compared with 5-year extended follow-up from the RATHL trial

Abstract

Treatment with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated(e)-BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) remains the international standard of care for advanced-stage classical Hodgkin lymphoma (HL). We performed a retrospective, multicentre analysis of 221 non-trial (“real-world”) patients, aged 16–59 years, diagnosed with advanced-stage HL in the Anglia Cancer Network between 2004 and 2014, treated with ABVD or eBEACOPP, and compared outcomes with 1088 patients in the Response-Adjusted Therapy for Advanced Hodgkin Lymphoma (RATHL) trial, aged 18–59 years, with median follow-up of 87.0 and 69.5 months, respectively. Real-world ABVD patients (n=177) had highly similar 5-year progression-free survival (PFS) and overall survival (OS) compared with RATHL (PFS 79.2% vs 81.4%; OS 92.9% vs 95.2%), despite interim positron-emission tomography-computed tomography (PET/CT)-guided dose-escalation being predominantly restricted to trial patients. Real-world eBEACOPP patients (n=44) had superior PFS (95.5%) compared with real-world ABVD (HR 0.20, p=0.027) and RATHL (HR 0.21, p=0.015), and superior OS for higher-risk (international prognostic score ≥3 [IPS 3+]) patients compared with real-world IPS 3+ ABVD (100% vs 84.5%, p=0.045), but not IPS 3+ RATHL patients. Our data support a PFS, but not OS, advantage for patients with advanced-stage HL treated with eBEACOPP compared with ABVD and suggest higher-risk patients may benefit disproportionately from more intensive therapy. However, increased access to effective salvage therapies might minimise any OS benefit from reduced relapse rates after frontline therapy.

Guideline for the first‐line management of Classical Hodgkin Lymphoma — A British Society for Haematology guideline

“…With median 69 months follow-up in RATHL, patients aged 18-59 had a PFS of 81.4%. 23 Both trials identified similar proportions of iPET-positive patients (16% in RATHL and 18% in SWOG) and despite dose escalation, PFS of iPET-positive patients remained 10% to 17% inferior to that of iPET-negative patients. The use of radiotherapy was not mandated and only 6.5% of patients in RATHL had consolidation radiotherapy.…”

“…With 5.9 years follow‐up in the SWOG trial, five‐year PFS was 74%. With median 69 months follow‐up in RATHL, patients aged 18–59 had a PFS of 81.4% 23 . Both trials identified similar proportions of iPET‐positive patients (16% in RATHL and 18% in SWOG) and despite dose escalation, PFS of iPET‐positive patients remained 10% to 17% inferior to that of iPET‐negative patients.…”

“…The rest will require intensification either after iPET2 or following a later relapse. Subanalysis of RATHL data 23 showed that IPS3+ patients have higher iPET‐positive rates than IPS 0–2 patients (22.1% vs 12.9%) and a higher five‐year relapse rate (23.7% vs 15.9%). Stage 4 patients also have a high five‐year relapse rate (23%).…”

Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics

“…The extended combination seems to be slightly more effective than ABVD in leukemia treatment, as presented in a pooled analysis of four independent clinical trials [ 94 ]. In non-Hodgkin lymphoma, BEACOPP is more effective than ABVD in progression-free survival but not in overall survival [ 95 ]. The statistical data confirm that the strategy of using wider drug combinations, especially when vincristine is included, represents the right way in modern cancer treatment.…”

Navigating increasingly individualised Hodgkin lymphoma treatments to optimally balance risks and benefits

“…In advanced stage disease, the authors recommend a PET‐2‐guided approach with either 4–6 × eBEACOPP (GHSG HD18), 9 2 × BEACOPP plus 4 × eBEACOPP or 4 × ABVD (AHL2011) 10 or 2 × ABVD plus 4 × ABVD or 4 × AVD (RATHL), 11 each with 30 Gy RT only administered to PET‐positive residues. However, the prognostic impact of PET seems to be dependent on the initial treatment regimen.…”