BEACOPP Chemotherapy Is Able to Induce Durable Complete Remission in Poor-Prognosis Hodgkin’s Lymphoma Patients with a Positive Interim PET after 2 ABVD Cycles

Background: Early interim-PET (PET-2) is the most powerful factor able to predict treatment outcome in advanced-stage Hodgkin Lymphoma (HL) patients treated with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). The 2-y PFS of PET-2 positive patients is only 12%, but the optimal treatment for this patient subset is still unknown. For this reason in January 2006 a treatment policy was designed by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) to early intensify chemotherapy with BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) for HL patients with a PET-2 positive after 2 ABVD cycles.

Patients and methods: 136 HL patients with advanced-stage or intermediate-stage with adverse prognostic factors (more than 3 nodal sites, ESR > 50 mm, sub diaphragmatic presentation, bulky lesion), consecutively admitted to nine GITIL Italian centers were treated with two ABVD courses and re-evaluated with interim-PET. Twenty-one of these 136 patients proved to be PET-2 positive, and 19/21 are the object of this analysis. The mean age was 31.7 years (16–64), 10 patients were in stage II, 9 in stage III–IV. Bulky disease was present in 11, and B-symptoms in 16. Fourteen patients showed an IPS score 0–2, 5 patients a score 3–7. The median interval between the end of second ABVD course and PET-2 was 11 days (5–14). BEACOPP (4 escalated and 4 standard cycles) was followed by consolidation radiotherapy in 3 patients for bulky mediastinal tumor. PET scan were centrally reviewed by two well-experienced nuclear medicine experts, using the blood pool mediastinal structures (BPMS) as reference for the residual uptake, as elsewhere published (Gallamini, JCO 2007).

Results. Upon central review, 2 interim-PET scan were classified as minimally positive in 2 patients, with a single MRU (Minimal Residual Uptake) lesion showing a SUV (Standardized Uptake Value) lower than BPMS, and therefore only 19 cases were suitable for the BEACOPP salvage treatment. After a mean follow-up of 14.3 months (7.0–30.2), 15 patients remain in continuous CR and 4 had a treatment failure because of disease relapse (1) or progression (3). For the responding patients the mean duration of CR was 13.0 months (6.5–30.2). The IPS score for progressing patients was 2, 3, and 4; for the relapsing-one, 0. At time of this analysis, l8 patients are still alive and 1 died during BEACOPP treatment for disease progression. The 1-year second treatment failure-free survival (1-y 2TFFS) was 94.7 % (95% C.I. 84.7–100). The 1 y OS survival was 93.3 (95%C.I. 80.7–100). In univariate analysis the only clinical factor related to treatment failure was the presence of extra-nodal disease. (Log-rank=6.8 p=0.009).

Conclusions. BEACOPP-escalated regimen was able to induce durable CR in most (15/19) HL patients with a positive interim-PET. These results, although requiring a longer follow-up and a higher number of patients, seem to suggest that

1. the very-poor prognosis of PET-2 positive, ABVD-treated HL patients can be substantially improved by early chemotherapy intensification;

2. escalated-BEACOPP is likely to represent a good treatment choice for this very poor prognosis patient subset.