DOSE DENSE ABVD (DD-ABVD) AS FIRST LINE THERAPY IN EARLY-STAGE UNFAVORABLE HODGKIN LYMPHOMA (HD): RESULTS OF A PHASE II, PROSPECTIVE STUDY BY FONDAZIONE ITALIANA LINFOMI

Four cycles of ABVD followed by 30Gy involved site radiotherapy (ISRT) is the standard of care in unfavourable classical Hodgkin lymphoma (HL). Since dose‐density might represent an important factor to achieve complete remission and longterm survival, we designed a trial to evaluate dose‐dense ABVD (ddABVD) in ptinents (pts) with early unfavourable HL. This prospective, multicentric, phase 2 study enrolled pts aged 18–70 years with newly diagnosed cHL, unfavourable stage I or II (EORTC criteria). Stage IIB bulky were excluded. Aims of the study were feasibility, safety and efficacy of ddABVD. DdABVD 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 ddABVD followed by ISRT were administered. Interim PET was mandatory after 2 courses (PET2). Pts experiencing PD were shifted to second‐line therapy. Feasibility and activity of ddABVD were the primary endpoints of the study. By design, the study was considered feasible if ≤5 out of 52 pts required a dose reduction below 85% of the planned dose. The percentage of PET2 negativity was chosen as the parameter to evaluate its activity. Between Feb 2012 and Jun 2015, 96 pts were enrolled and evaluated. The feasibility endpoint was achieved with only 4 out of 52 pts requiring a dose reduction greater than 15%. The mean dose intensity in the 96 pts who started ddABVD treatment was 93.7% with only 3 pts unable to complete ddABVD due to toxicity. The activity analysis was performed in all 96 pts. PET‐2 was available for 92/96 (95.8%) pts: 79 were PET2 negative (85.9%) and 13 PET2 positive (14.1%). In 4 pts PET2 wasn't performed (3 logistic reasons, 1 switched to standard ABVD due to a SAE at cycle 1). Considering the global outcome of the 96 pts who received at least 1 ddABVD course: 90 pts achieved CR (93.8%), 1 PR (1%), 4 PD (4.2%) and 1 (1%) was without a known disease assessment. With a median followup of 39.9 months (2.1‐ 57.6), median PFS and OS were not reached, at 24 months PFS and OS were 91.5% and 97.9%. No statistically significant differences were observed for PET2 negative and PET2 pts for both 2 years PFS (94.9% vs 84.6%, p:0.260) and OS (98.7% vs 100% a, p:0.560). 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 1 toxic death after cycle 4; 3 pts were discontinued due to toxicity and were switched to standard ABVD or AVD. The study demonstrates the feasibility of ddABVD in early unfavourable cHL which also allows a reduction in overall treatment duration without a significant increase in toxicity. The dose‐dense strategy translated in excellent outcome in term of CR rate, PFS, OS with a low rate of PR at 2 years. DdABVD deserves further comparison with conventional ABVD.