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Abstract

BACKGROUND:

We tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma.

METHODS:

Patients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PET-CT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points.

RESULTS:

A total of 1214 patients were registered; 937 of the 1119 patients (83.7%) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7% (95% confidence interval [CI], 82.1 to 88.6) and 97.2% (95% CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4% (95% CI, 80.7 to 87.5) and 97.6% (95% CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95% CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4% had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5% and the overall survival rate 87.8%. A total of 62 patients died during the trial (24 from Hodgkin's lymphoma), for a 3-year progression-free survival rate of 82.6% and an overall survival rate of 95.8%.

CONCLUSIONS:

Although the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy. (Funded by Cancer Research UK and Others; ClinicalTrials.gov number, NCT00678327.).

Comment in

Fine-Tuning the Treatment of Hodgkin's Lymphoma. [N Engl J Med. 2016] 

Author information​

Johnson P1, Federico M1, Kirkwood A1, Fosså A1, Berkahn L1, Carella A1, d'Amore F1, Enblad G1, Franceschetto A1, Fulham M1, Luminari S1, O'Doherty M1, Patrick P1, Roberts T1, Sidra G1, Stevens L1, Smith P1, Trotman J1, Viney Z1, Radford J1, Barrington S1.

1From the Cancer Research UK Centre, University of Southampton, Southampton (P.J.), Cancer Research UK and University College London Cancer Trials Centre (A.K., P.P., T.R., L.S., P.S.) and the PET Imaging Centre, King's College London, King's Health Partners, St. Thomas' Hospital (M.O., Z.V., S.B.), London, the Department of Haematology, Lincoln County Hospital, Lincoln (G.S.), and the Department of Medical Oncology, Christie Hospital, Manchester (J.R.) - all in the United Kingdom; the Department of Diagnostic, Clinical, and Public Health Medicine, University of Modena and Reggio Emilia, Modena (M. Federico, A. Franceschetto, S.L.), the Department of Hematology, San Martino University Hospital, Genoa (A.C.), and Arcispedale Santa Maria Nuova-Istituti di Ricovero e Cura a Carattere Scientifico, Reggio Emilia (S.L.) - all in Italy; the Department of Medical Oncology, Oslo University Hospital, Oslo (A. Fosså); the Department of Haematology, Auckland City Hospital, Auckland, New Zealand (L.B.); the Department of Hematology, Aarhus University Hospital, Aarhus, Denmark (F.A.); the Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden (G.E.); and the Department of Molecular Imaging, Royal Prince Alfred Hospital (M. Fulham), and Concord Repatriation General Hospital, University of Sydney (J.T.), Sydney.