Administering an intensified regimen of BEACOPP chemotherapy (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine [Matulane], and prednisone) to patients with interim PET-positive advanced Hodgkin lymphoma (HL) after treatment with two courses of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) may be superior to continuing treatment with four additional courses of ABVD, according to results of a phase II (non-randomized) trial presented at the 2010 ASCO Annual Meeting.¹ Use of escalated BEACOPP in this high-risk group boosted 2-year progression-free survival (PFS) compared to historical data.

The 2-year PFS rate in patients with advanced HL who remain PET positive after ABVD has been suggested to be around 10% to 12%. In this study, 64% of PET-positive patients were alive and progression-free at 2 years, presumably because they received escalated BEACOPP.

"Interim PET-positive scans after two courses of ABVD is the most powerful prognostic tool for advanced HL in predicting treatment outcome. Our study sought to address whether we could change the destiny of PET-positive patients after two courses of ABVD by giving them BEACOPP. In other words, we wanted to see if there is an advantage in this cohort of giving intensified chemotherapy," said senior author of this paper, Andrea Gallamini, MD, of Santa Croce Hospital in Cuneo, Italy.

Dr. Gallamini added, "Another question posed by our study was this: Could the overall PFS of this entire cohort of advanced-stage HL patients-among whom a small subset of interim PET-positive patients received intensified chemotherapy with BEACOPP-be improved by this strategy, as compared with historic ABVD-treated control patients? The answer is probably yes, because the 2-year PFS of advanced-stage, ABVD-treated historical control patients was 80% to 85%, as opposed to about 91% in our study. However, longer follow-up is needed to confirm these results."

Some physicians reserve the use of BEACOPP for high-risk patients because it is highly myelotoxic. In this study, a less toxic regimen of ABVD was given up front to patients with advanced HL, and escalated BEACOPP was given to those with interim PET-positive scans but not to those with PET-negative scans. This approach spared the PET-negative patients from the short- and long-term toxicity associated with BEACOPP, Dr. Gallamini explained.

Study Details

The investigation was based on pooled patients (n = 162) from eight centers in Italy and one in the United States. All patients enrolled in the trial had advanced-stage HL, and all were treated initially with two courses of ABVD followed by an interim PET scan. Less than 25% of these patients had high-risk advanced-stage disease (ie, International Prognostic Index score > 3). The interim PET-positive patients (n = 27) were given four courses of escalated BEACOPP and then four courses of standard ­BEACOPP, followed by consolidation radiotherapy. The interim PET-negative group (n = 135) was treated with four additional courses of ABVD followed by consolidation radiotherapy.

The investigators found no differences in pretreatment patient characteristics between the two arms. At a mean follow-up of 26 months, 2-year PFS in 158 evaluable patients was 92.5% in the PET-negative group vs 64% in the PET-positive group. Some discordance arose in interpreting the interim PET scans in six patients whose initial classification as positive or negative by the local PET reviewer changed upon central review. Thus, these six patients were incorrectly treated according to the study protocol. Taking these six patients out of the analysis, 2-year PFS was 96.2% in the PET-negative group vs 60.5% in the PET-positive group.

"This approach [in PET-positive patients] is now being studied prospectively in multiple trials that are running worldwide," Dr. Gallamini told listeners. ■

Reference

1. Fiore F, Patti K, Viviani S, et al: Effect of early intensification with BEACOPP in high-risk interim-PET positive, advanced-stage Hodgkin lymphoma on overall treatment outcome of ABVD. 2010 ASCO Annual Meeting. Abstract 8006. Presented June 5, 2010.