Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma

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.).

Figure 1. Registration and Randomization of the Patients and Outcomes of Positron-Emission Tomography–Computed Tomography (PET-CT).

PET findings on the interim PET-CT scan were scored with the use of a 5-point scale, according to the level of any residual uptake of ¹⁸F-fluorodeoxyglucose at involved sites on baseline PET and with higher scores indicating greater uptake. A score of 1, 2, or 3 was regarded as indicating negative findings, and a score of 4 or 5 was regarded as indicating positive findings. BEACOPP-14 is an accelerated version of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) that involves growth-factor support. Escalated BEACOPP involves higher-than-standard doses of etoposide, doxorubicin, and cyclophosphamide. ABVD denotes doxorubicin, bleomycin, vinblastine, and dacarbazine, AVD doxorubicin, vinblastine, and dacarbazine, DLBCL diffuse large-B-cell lymphoma, and NLPHL nodular lymphocyte-predominant Hodgkin’s lymphoma.

Figure 2. Progression-free and Overall Survival.

Panel A shows progression-free survival among patients with negative PET findings after two cycles of ABVD who underwent randomization, Panel B overall survival among patients with negative PET findings who underwent randomization, Panel C progression-free survival among patients with positive PET findings, and Panel D overall survival among patients with positive PET findings.