A phase II study of dose‐dense and dose‐intense ABVD (ABVD_DD‐DI) without consolidation radiotherapy in patients with advanced Hodgkin lymphoma

Abstract

SummaryWe explored activity and safety of a dose-dense/dose-intense adriamycin, bleomycin, vinblastine and dacarbazine regimen (ABVD DD-DI ) in 82 patients with advanced Hodgkin Lymphoma. Patients entered a two-stage Bryant-Day Phase II study to receive six cycles of ABVD DD-DI without consolidation radiotherapy. Cycles were supported with granulocyte colonystimulating factor and delivered every 21 d; drugs were administered on days 1 and 11 at the same doses of standard ABVD except for doxorubicin (35 mg/m 2 ; first four cycles only). Co-primary endpoints were complete response (CR) rate and severe acute cardiopulmonary toxicity; secondary endpoints were event-free (EFS) and disease-free survival (DFS). All patients received the four doxorubicin-intensified courses and 96% concluded all six cycles (82Á3% within the intended 18 weeks). This translated into a 66Á9% increase of received dose-intensity for doxorubicin and 31Á8% for the other agents over standard ABVD. The CR rate was 95Á1% (78/82) and 87Á8% (72/82) achieved a metabolic CR after two cycles. Cardiopulmonary toxicity never exceeded grade 2 and affected 14Á6% of patients. Most frequent toxicities were grade 4 neutropenia (10%) and anaemia (9%), grade 3 infection (17%) and grade 2 mucocutaneous changes (30%). Fiveyear EFS and DFS was 88Á3% and 93Á7%, respectively. ABVD DD-DI regimen was well-tolerated and ensured substantial CR and EFS rates without radiotherapy.

Feasibility and efficacy of dose‐dense and dose‐intense ABVD for high‐risk patients with advanced Hodgkin lymphoma

“…In line with the pivotal ABVD DD‐DI trial (Russo et al , ), we confirm that a high response rate can be achieved also in patients with high‐risk features and support that intensification of the ABVD programme is feasible in ‘real‐life’ clinical practice, without a demanding management and burdening toxicity. In this regard, ABVD DD‐DI results may favourably match, in terms of CR rate, early PET‐negativity and acute toxicity, with those of escalated BEACOPP (Skoetz et al , ).…”

“…A recent report highlighted the promising results of a phase II trial of dose‐dense (DD) and dose‐intense (DI) ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine; ABVD DD‐DI ) in advanced classical Hodgkin lymphoma (HL) (Russo et al , ). In this study, a dose‐powered ABVD variant was administered to 82 patients on a three‐weekly basis without encumbering toxicities and with remarkable response and event‐free survival rates.…”

“…The analysis of long‐term survival outcomes from the ABVD DD‐DI phase II trial also hypothesized that consolidation RT may be redundant in patients achieving CR after intensified chemotherapy (Russo et al , ). Similarly, in our series, none of the complete responders received consolidation RT.…”

“…On the other hand, management of patients with 18 F‐FDG uptakes persisting beyond Cycle 4 of ABVD DD‐DI , was not addressed in the phase II trial because such patients were considered failures ‘per protocol’ and exited the study (Russo et al , ). In our series only two (14%) patients maintained 18 F‐FDG‐PET positivity after completion of chemotherapy, one of whom had a PR to CR conversion upon consolidation RT.…”

Feasibility and efficacy of dose‐dense and dose‐intense ABVD for high‐risk patients with advanced Hodgkin lymphoma: reply to D'Arco et al

“…We read with deep interest the report of D'Arco et al (), presenting a series of newly diagnosed patients with advanced Hodgkin lymphoma (HL) treated according to the dose‐dense (DD) and dose‐intense (DI) ABVD schedule (doxorubicin, bleomycin, vinblastine, dacarbazine: ABVD DD‐DI ) described in a phase II study from our group (Russo et al , ).…”