PS1237 DOSE DENSE ABVD (DD‐ABVD) AS FIRST LINE THERAPY IN EARLY‐STAGE UNFAVOURABLE HODGKIN LYMPHOMA (CHL): RESULTS OF A PHASE II, PROSPECTIVE, MULTI‐CENTER STUDY BY FONDAZIONE ITALIANA LINFOMI

Background: Four cycles of ABVD followed by 30 Gy involved site radiotherapy (ISRT) is the standard of care for patients with early unfavourable classical Hodgkin lymphoma (cHL). Since dose‐density might represent an important factor to achieve complete remission and longterm survival, we designed a prospective, multicenter, phase II trial to investigate feasibility, safety and efficacy of dose‐dense ABVD (dd‐ABVD) in patients with early unfavourable HL. This prospective, multicentric, phase 2 study enrolled patients aged 18–70 years with newly diagnosed cHL, unfavourable stage I or II, according to EORTC prognostic criteria. Patients with stage IIB bulky were excluded. Aims: Aims of the study were to investigate feasibility, safety and efficacy of dd‐ABVD in patients with early unfavorable cHL. Methods: Dd‐ABVD consists of Doxorubicin, Bleomycin, Vinblastine and Dacarbazine used at the same doses of conventional ABVD but is administered on days 1 and 8 every 3 weeks instead of days 1 and 15 every 4 weeks. In the absence of progressive disease (PD) or unacceptable toxicity, 4 cycles of dd‐ABVD followed by ISRT were administered. Interim PET was mandatory after 2 courses (PET‐2). Patients experiencing PD were shifted to second‐line salvage therapy. Feasibility and activity of dd‐ABVD regimen were the primary endpoints of the study. By design, the study was considered feasible if ≤5 out of 52 patients required a dose reduction below 85% of the planned dose. The percentage of interim PET negativity was chosen as the parameter to evaluate its activity. Results: Between February 2012 and June 2015, 96 patients were enrolled and evaluated. The feasibility endpoint was achieved with only 4 out of 52 patients requiring a dose reduction greater than 15%. The mean dose intensity in the 96 patients who started dd‐ABVD treatment was 93.7% with only 3 patients unable to complete ddABVD chemotherapy due to toxicity. The activity analysis was performed in all 96 patients. PET‐2 was available for 92/96 (95.8%) patients, of whom 79 were PET‐2 negative (85.9%) and 13 PET‐2 positive (14.1%). In 3 cases PET‐2 was not performed due to logistic reasons and in 1 patient because of switch to standard ABVD following a SAE at cycle 1. Considering the global outcome of the 96 patients who received at least 1 dd‐ABVD course: 90 patients achieved CR (93.8 %), 1 PR (1%), 4 PD (4.2 %) and 1 (1%) was without a known disease assessment. With a median follow‐up of 39.9 months (range: 2.1‐ 57.6 months), median PFS and OS were not reached, at 24 months PFS and OS were 91.5% and 97.9%, respectively. No statistically significant differences were observed for PET‐2 negative and PET‐2 positive patients for both 2 years PFS (94.9% vs 84.6%, p: 0.260) and OS (98.7% vs 100% a, p: 0.560) (figure 1). Most frequent toxicities were haematological. The infection rate was low (infection 8.3% and febrile neutropenia 6.25%); no patient developed cardiac toxicity until now. There was one toxic death after cycle 4; 3 patients were discontinued from the study due to toxicity and were switched to standard ABVD or AVD Summary/Conclusion: The study demonstrates the feasibility of the dd‐ABVD regimen in early unfavourable cHL which also allows a reduction in overall treatment duration without a significant increase in toxicity. Moreover, the dose‐dense strategy translated in excellent data of outcome in term of CR rate, PFS, and OS with a low rate of progression at 2 years. Dd‐ABVD deserves further comparison with conventional ABVD in early unfavourable as well in advanced cHL. image

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