US Intergroup Trial of Response-Adapted Therapy for Stage III to IV Hodgkin Lymphoma Using Early Interim Fluorodeoxyglucose-Positron Emission Tomography Imaging: Southwest Oncology Group S0816

Abstract

Purpose: Four US National Clinical Trials Network components (Southwest Oncology Group, Cancer and Leukemia Group B/Alliance, Eastern Cooperative Oncology Group, and the AIDS Malignancy Consortium) conducted a phase II Intergroup clinical trial that used early interim fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to determine the utility of response-adapted therapy for stage III to IV classic Hodgkin lymphoma.

Patients and methods: The Southwest Oncology Group S0816 (Fludeoxyglucose F 18-PET/CT Imaging and Combination Chemotherapy With or Without Additional Chemotherapy and G-CSF in Treating Patients With Stage III or Stage IV Hodgkin Lymphoma) trial enrolled 358 HIV-negative patients between July 1, 2009, and December 2, 2012. A PET scan was performed after two initial cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and was labeled PET2. PET2-negative patients (Deauville score 1 to 3) received an additional four cycles of ABVD, whereas PET2-positive patients (Deauville score 4 to 5) were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for six cycles. Among 336 eligible and evaluable patients, the median age was 32 years (range, 18 to 60 years), with 52% stage III, 48% stage IV, 49% International Prognostic Score 0 to 2, and 51% score 3 to 7.

Results: Three hundred thirty-six of the enrolled patients were evaluable. Central review of the interim PET2 scan was performed in 331 evaluable patients, with 271 (82%) PET2-negative and 60 (18%) PET2-positive. Of 60 eligible PET2-positive patients, 49 switched to eBEACOPP as planned and 11 declined. With a median follow-up of 39.7 months, the Kaplan-Meier estimate for 2-year overall survival was 98% (95% CI, 95% to 99%), and the 2-year estimate for progression-free survival (PFS) was 79% (95% CI, 74% to 83%). The 2-year estimate for PFS in the subset of patients who were PET2-positive after two cycles of ABVD was 64% (95% CI, 50% to 75%). Both nonhematologic and hematologic toxicities were greater in the eBEACOPP arm than in the continued ABVD arm.

Conclusion: Response-adapted therapy based on interim PET imaging after two cycles of ABVD seems promising with a 2-year PFS of 64% for PET2-positive patients, which is much higher than the expected 2-year PFS of 15% to 30%.

Fig 1.

CONSORT diagram demonstrating patient flow of 358 patients enrolled in the Southwest Oncology Group S0816 trial. ABVD, doxorubicin, bleomycin, vinblastine, and dacarbazine; CT, computed tomography; eBEACOPP, escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone; G-CSF, granulocyte colony-stimulating factor; IPS, International Prognostic Score; PET, positron emission tomography; RT, radiotherapy.

Fig 2.

Overall and progression-free survival for 336 patients with Hodgkin lymphoma treated with response-adapted therapy on the Southwest Oncology Group S0816 trial, regardless of interim positron emission tomography/computed tomography scan result or treatment arm.

Fig 3.

Progression-free survival of 331 evaluable patients with Hodgkin lymphoma treated with response-adapted therapy on the Southwest Oncology Group S0816 trial.

Fig 4.

Progression-free survival of 331 evaluable patients with Hodgkin lymphoma treated with response-adapted therapy on the Southwest Oncology Group S0816 trial. Patients were stratified by Deauville score assessed via centralized positron emission tomography (PET) review of the fluorodexoxyglucose-PET interim scan performed after two cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine. Only five patients had a Deauville score of 5 after two cycles of ABVD, so they are combined with the 55 patients with a Deauville score of 4.