PET-Adapted Treatment in Newly Diagnosed Advanced Hodgkin Lymphoma
In the phase III AHL2011 trial reported in The Lancet Oncology, Casasnovas et al found that positron-emission tomography (PET)-guided treatment produced good outcomes in newly diagnosed advanced Hodgkin lymphoma, allowing de-escalation of induction to ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in early responders with no loss of disease control and reduced toxicity.
Study Details
In the open-label, noninferiority trial, 823 patients from 90 sites in France and Belgium were randomly assigned between May 2011 and April 2014 to receive standard treatment with escalated BEACOPP (increased-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) given every 21 days for six cycles (n = 413) or PET-driven treatment (n = 410).
All patients received two cycles of upfront escalated BEACOPP and then underwent PET assessment (PET2). Patients in the standard treatment group completed two additional cycles of escalated BEACOPP induction, irrespective of PET2 findings. Patients in the PET-driven group with positive PET2 scans received the additional two cycles of escalated BEACOPP, whereas those with a negative scan switched to two cycles of ABVD for remaining induction therapy. PET at the end of induction in both groups was used to determine whether to continue consolidation therapy in those with negative scans or to provide salvage therapy in patients with positive scans (two cycles of ABVD in PET2-negative patients in the PET-driven group or two cycles of escalated BEACOPP).
The primary endpoint was investigator-assessed progression-free survival.
Progression-Free Survival
A total of 346 patients (84%) in the PET-driven treatment group received ABVD after PET2. With median follow-up of 50.4 months, 5-year progression-free survival on intent-to-treat analysis was 86.2% in the standard treatment group vs 85.7% in the PET-driven group (difference within the noninferiority margin of 10%; hazard ratio [HR] = 1.084, P = .65); on per-protocol analysis, rates were 86.7% vs 85.4% (HR = 1.144, P = .74). Overall survival at 5 years was 95.2% vs 96.4% (HR = 0.936, P = .43) on intent-to-treat analysis and 95.6% vs 95.9% on per-protocol analysis (HR = 1.248, P = .69).
Adverse Events
The most common grade 3 or 4 adverse events were leukopenia (92% in standard treatment group vs 95% in PET-driven group), neutropenia (87% vs 90%), anemia (69% vs 28%), thrombocytopenia (66% vs 40%), febrile neutropenia (35% vs 23%), infections (22% vs 11%), and gastrointestinal disorders (11% vs 11%). Treatment-related serious adverse events occurred in 47% vs 28% of patients, including infections in 20% vs 12% and febrile neutropenia in 5% vs 6%. Treatment-related adverse events resulted in death in six patients in the standard treatment group (septic shock in two, pneumopathy in two, heart failure in one, and acute myeloblastic leukemia in one) and two patients in the PET-driven group (septic shock in one and acute myeloblastic leukemia in one).
The investigators concluded, “PET after two cycles of induction escalated BEACOPP chemotherapy safely guided treatment in patients with advanced Hodgkin lymphoma and allowed the use of ABVD in early responders without impairing disease control and reduced toxicities. PET staging allowed accurate monitoring of treatment in this trial and could be considered as a strategy for the routine management of patients with advanced Hodgkin lymphoma.”
René-Olivier Casasnovas, MD, of the Department of Haematology, University Hospital F. Mitterrand and Inserm UMR 1231, Dijon, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the Programme Hospitalier de Recherche Clinique. The study authors’ full disclosures can be found at thelancet.com.
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