In the present study, we evaluated the efficacy and safety of rituximab in combination with standard doxorubicin, bleomycin, vinblastine, and dacarbazine (RABVD) in patients with classical Hodgkin lymphoma (cHL). In this phase 2 study, patients with chemotherapy-naive, advanced-stage cHL were treated with rituximab 375 mg/m 2 weekly for 6 weeks and standard ABVD for 6 cycles. The primary outcome was event-free survival (EFS) at 5 years. Eighty-five patients were enrolled, of whom 78 were eligible. With a median follow-up duration of 68 months (range, 26-110), and based on an intent-totreat analysis, the 5-year EFS and overall survival rates were 83% and 96%, respectively. The 5-year EFS for patients with stage III/IV cHLwas 82%. Furthermore, the 5-year EFS for patients with an International Prognostic Score of 0-2 was 88% and for those with a score of > 2, it was 73%. The most frequent treatment-related grade 3 or 4 adverse events were neutropenia (23%), fatigue (9%), and nausea (8%). Our results demonstrate that the addition of rituximab to ABVD is safe and has a promising clinical activity in patients with advanced-stage cHL. These data are currently being confirmed in a multicenter randomized trial. This trial has been completed and is registered with www.
IntroductionThe majority of patients with newly diagnosed classical Hodgkin lymphoma (cHL) are cured with initial multiagent chemotherapy. Among multiple chemotherapy regimens, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) remain the most widely used regimen for the treatment of patients with advanced-stage cHL. 1-7 Because undesired short-and long-term treatment-related toxicity continues to be problematic for this relatively young patient population, the development of more safe and effective frontline regimens continues to be actively pursued. [8][9][10] The anti-CD20 mAb rituximab has demonstrated a good safety profile and clinical activity in a wide variety of B-cell lymphomas, all of which express the CD20 Ag on the malignant B cells. Subsequent studies combining rituximab with frontline chemotherapy regimens resulted in improvement in the event-free survival (EFS) and, in several cases, in the overall survival (OS) of patients with different non-Hodgkin lymphoma subtypes. 11,12 In Hodgkin lymphoma, the malignant cells express CD20 of the lymphocyte-predominant subtype, but only in 20%-30% of the cHL subtype. [13][14][15][16] In those cases, rituximab also demonstrated single-agent activity. 17 Emerging data have suggested that rituximab may also have therapeutic value in patients with cHL whose tumors do not express CD20 by either depleting reactive B lymphocytes from the microenvironment, which may enhance antitumor immunity, 18 or by killing the putative CD20-expressing HL stem cells. 19 With this background, we conducted a phase 2 study to evaluate the safety and efficacy of rituximab in combination with standard ABVD chemoth...