Multicenter phase II study of rituximab-ABVD in classic Hodgkin lymphoma (cHL).

Abstract

8039 Background: Unlike Hodgkin and Reed Sternberg (HRS) cells, cHL cancer stem cells (CSC) may have a CD20+, memory B cell phenotype and circulate in high frequencies (Jones RJ et al, Blood 2009;113:5920), potentially explaining rituximab’s activity in cHL. Methods: An inter-SPORE study of rituximab-ABVD, to explore the activity of rituximab in cHL using both correlative assays of cHL CSC and clinical outcome, was conducted and accrual completed in 6/2009. Eligibility criteria included stage II, III or IV untreated cHL; age ≥ 18 y; HIV and hepatitis B surface antigen negative; creatinine ≤ 2 mg/dL; bilirubin ≤ 5 mg/dL. Planned treatment was 6 cycles of ABVD with addition of rituximab 375 mg/m2 1 week prior to first ABVD; on days 1, 8, 15, 22 of cycle 1 ABVD; and on day 1 of cycles 2, 4, 6. Dose delays, growth factors and radiation were at physician discretion. Results: Clinical outcomes of all 49 evaluable patients (pts) are presented. Median age was 33 (range 18-66); 26 (53%) were male; stage was IIA in 15 pts, IIB in 5, III-IV in 29 (59%); and 17 (35%) had bulky mediastinal disease. HRS cells were CD20+ in 4 of 47 cases assessed (8.5%). International Prognostic Score (IPS) was 0-1 in 20 pts (41%); 2 in 14 (29%); ≥ 3 in 15 (31%). In urgent cases omission of first rituximab was permitted, and this occurred in 17 pts (35%). Addition of rituximab was generally well tolerated. One death from sepsis occurred during cycle 2. Mean delivered relative dose intensity with 6 cycles was high: 92% for the ABVD combination (96% for AVD, 80% for bleomycin). After 6 cycles, 39 pts (81%) had CR, 6 (12.5%) PR, 1 SD (2%), 2 (4%) progressive disease by 2007 IWG criteria. Only 4 pts received radiation. On centralized review of cycle 2 PET (41 pts), 36 (88%) were PET negative (tumor uptake < liver) and 5 (12%) were PET positive by modified London criteria. Pts with positive interim PET had inferior EFS (P < 0.004). With median 28 month follow-up (range 1.5-48 months), actuarial EFS after treatment initiation is 92% at 2 y and 83% at 3 y (90% at 3 y if IPS ≥ 2). Actuarial overall survival is 98%. Analysis of biomarkers in relation to disease status is ongoing to define cHL CSC biology. Conclusions: Rituximab-ABVD yields encouraging clinical results in cHL, despite a minority of tumors expressing CD20.