Rituximab + ABVD Improves Event-Free Survival (EFS) in Patients with Classical Hodgkin Lymphoma in All International Prognostic Score (IPS) Groups and in Patients Who Have PET Positive Disease after 2–3 Cycles of Therapy.

The use of rituximab in classical Hodgkin lymphoma (HL) has been proposed to have a therapeutic value by several mechanisms;

1. to The malignant Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL) rarely survive outside their microenvironment of reactive B-cells, and therefore we hypothesized that depleting B-cells from HL microenvironment by rituximab may deprive HRS cells from critical survival and resistance factors and therefore improving the efficacy of chemotherapy,

2. Rituximab may have a direct killing effect on HRS cells that express CD20, and

3. recent data from Johns Hopkins Medical Center suggested that HRS stem cells are CD20+ cells.

With this background, we evaluated the safety and efficacy the combination of rituximab and ABVD (R-ABVD) chemotherapy in newly diagnosed patients with classical HL. In addition, PET after 2–3 cycles of ABVD has been shown to confer poor prognosis and therefore proposed to guide future therapy. (Hutchings et al, Blood, 2006) reported a negative PET scan after two cycles of ABVD to be a good predictor of outcome with 96% 2-year progression free survival (PFS). Those with PET positive after 2 cycles had a 0% PFS at 2 years. Thus, we examined the effect of RABVD on early PET imaging and determined whether PET status remains predictive of treatment outcome in patients receiving RABVD. To date 70 newly diagnosed pts are enrolled, of whom 65 pts had at least 12 months of follow up and are evaluable for treatment response. Median age 28 years (Range; 18–72 years). Patients had stage II (50%), stage III (31%), stage IV (19%) disease. Using the IPS prognostic score model, 36 patients (55%) had a score of 2 or higher. With a median follow up of 32 months, the estimated event-free survival (EFS) is for the entire group is 85% and overall survival 98%. EFS for patients with IPS 0–1, 2, and >2 are 95%, 76%, and 77%, respectively, suggesting that R-ABVD improved EFS in all IPS scores with the biggest impact seen in patients with IPS > 2. 55 patients had PET after 2–3 cycles and were included in the predictive analysis of PET on treatment outcome. PET became negative in 43 patients (78%) after completing 2–3 cycles of RABVD and positive in the remaining 12 patients (22%). 5-year EFS for those with negative PET was 93% and 75% for those who remained PET positive (p=0.05). We conclude that in patients with classical HL, the addition of 6 weekly doses of rituximab to standard dose and schedule of ABVD chemotherapy is effective in terms of remission rate and remission duration irrespective of IPS category. Our data confirmed prior reports that patients who remain PET positive after 2–3 cycles have worse prognosis when compared to those that achieve PET negativity. However, the outcome for those who remained PET positive after 2–3 cycles of RABVD seems to be significantly better than what has been previously reported when using ABVD alone. A randomized trial comparing ABVD with RABVD is planned to confirm these observations.