Reduced intensity VEPEMB regimen compared with standard ABVD in elderly Hodgkin lymphoma patients: results from a randomized trial on behalf of the Fondazione Italiana Linfomi (FIL)

Abstract

Survival rates for elderly Hodgkin Lymphoma (HL) have not improved substantially in recent years, mainly because of a lack of prospective randomized studies, due to difficulties in enrolling patients. Between 2002 and 2006, 54 untreated HL patients, aged between 65 and 80 years and considered 'non-frail' according to a comprehensive geriatric evaluation, were enrolled into a phase III randomized trial to compare a reduced-intensity regimen (vinblastine, cyclophosphamide, procarbazine, prednisone, etoposide, mitoxantrone, bleomycin; VEPEMB) with standard ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). Primary endpoint was progression-free survival (PFS). Seventeen patients were in early stage (I-IIA), while 37 were advanced stage. Median age was 72 years and median follow-up was 76 months. Five-year PFS rates were 48% vs. 70% [adjusted Hazard ratio (HR) = 2·19, 95% confidence interval (CI) = 0·94-5·10, P = 0·068] and 5-year overall survival (OS) rates were 63% vs. 77% (adjusted HR = 1·67, 95% CI = 0·69-4·03, P = 0·254) for VEPEMB compared to ABVD. Overall treatment-related mortality was 4%. World Health Organization grade 4 cardiac and lung toxicity occurred in four patients treated with ABVD versus no cases in the VEPEMB arm. Standard ABVD regimen resulted in better PFS and OS than the VEPEMB, although the differences were not statistically significant. The low toxicity of both treatments was probably attributable to stringent selection of patients based on a Comprehensive Geriatric Assessment that excluded frail patients.

Hodgkin lymphoma in the elderly: new perspectives and a 10‐year monocenter real‐life experience

“…In the SHIELD study an attempt to reduce treatment intensity was made with VEPEMB regimen (vinblastine, cyclophosphamide, procarbazine, etoposide, mitoxantrone, bleomycin), including only 2 bleomycin doses . However, a randomized trial comparing VEPEMB with ABVD showed the same treatment‐related mortality with reduced progression‐free survival (PFS) for VEPEMB regimen …”

The treatment of older Hodgkin lymphoma patients

“…In the aforementioned VEPEMB study, Zallio et al () used co‐morbidity according to the CIRS, the ADL index, index of Instrumental Activity of Daily Living and Geriatric Depression Scale (GDS). Patients were defined as frail and excluded from the study, if they met one or several of the following conditions: age ≥80 years, ≥3 grade 3 comorbidities or ≥1 grade 4 comorbidity according to the CIRS scale, ADL score <6 and/or geriatric syndrome.…”

“…In contrast, mediastinal involvement and bulky lymphoma are less common in older compared to younger patients (Engert et al , ; Klimm et al , ). One important characteristic in older HL patients is their low tolerance to treatment due to pre‐existing comorbidities, resulting in dose reductions, therapy delays and, ultimately, excessive treatment‐related toxicity and mortality (Proctor et al , ; Böll et al , 2013a, ; Zallio et al , ; Björkholm et al , ). Remarkably this increased vulnerability towards therapy‐associated toxicity is not restricted to patients above the age of 60 years but treatment‐related toxicity and mortality is increased even at the age of 40 or 50 years compared to younger patients (Wongso et al , ; Björkholm et al , ).…”

Current treatment paradigms for advanced stage Hodgkin lymphoma

“…Interestingly, independent of chemotherapy regime, no patients who were ‘frail’ achieved a CR at the end of treatment (Proctor et al , ). A small randomised trial compared VEPEMB to ABVD in carefully‐selected non‐frail patients aged 65–80 years, and found the results with ABVD to be slightly better, with 5‐year PFS rates of 48% vs. 70% and OS 63% vs. 77%, although these differences were not significant owing to the small size of the study (Zallio et al , ). Similar results were seen in the RATHL trial, where the 5‐year PFS among 43 patients over 65 years was 65%, with a 5‐year OS of 83% (Johnson et al , ).…”