Rituximab (Rituxan) Combined with ESHAP Chemotherapy Is Highly Active in Relapsed/ Refractory Aggressive Non-Hodgkin’s Lymphoma.

Patients with relapsed/refractory aggressive lymphoma have limited options for achieving long-term remission other than stem cell transplantation. ESHAP is active in aggressive NHL and has the added advantage of being a non-anthracycline regimen. However, the response rate and remission duration with ESHAP chemotherapy alone are low in this group of patients. Encouraged by the increased efficacy of chemo-immunotherapy combinations like CHOP + Rituximab (Rituxan) in untreated aggressive lymphoma, and the in vitro synergy of Rituximab with cisplatin, cyclophosphamide and steroids, we studied the safety and efficacy of ESHAP + Rituximab combination in this group of patients. Standard ESHAP regimen (Etoposide 40 mg/m²/d IV/2h day1–4; Methylprednisolone 500 mg/m² IV days 1–4; Cytarabine 2 g/m² IV/3h day 5 and Cisplatin 25 mg/m²/d CIV days 1–4) was administered. Rituximab 375 mg/m² IV was administered in the following manner: 2 doses separated by one week prior to the first cycle of ESHAP and 2 doses administered similarly after completion of the sixth cycle of ESHAP; one dose of Rituximab each was also given 48 hours prior to the third and fifth cycle of ESHAP. Treatment cycles were repeated every 28 days x 6. GMCSF (Leukine) and Erythropoietin (Procrit) were used at the discretion of the investigator. 14 patients were enrolled in the study. Median age was 55.5 years (range 37–70); there were 12 males and 2 females. 11/14 (71%) of patients had advanced disease (stage III/IV). Extranodal disease sites included kidney, lungs and adrenals. Histology was Diffuse Large Cell: 13 (93%) and Mantle Cell Lymphoma: 1 (7%). All patients had prior therapy: 1^st relapse 11, 2^nd relapse 1 and 3^rd relapse 2. Prior therapies included CHOP, modified CHOP, Fludarabine-based regimen, Rituxan and Bexxar. 7 patients (50%) achieved CR, 2 PR, 1 stable disease and 4 PD. Among the 6 patients who received all 6 cycles of therapy, 4/6 (67%) achieved CR and 2/6 (33%) PR, (ORR 100%). Duration of response in patients who received all 6 cycles: All Responders: 26.3 months (1–53.3) and Patients who achieved CR: 35 months (24.1–53.3). Significant toxicity included grade III/IV hematologic in 43% and grade III/IV infection/febrile neutropenia in 21%.

Conclusion: ESHAP combined with Rituximab appears to be more active than ESHAP alone with no additional toxicity other than infusion-related adverse events in patients with relapsed/refractory aggressive lymphoma. Patients who achieved CR with this regimen appear to have longer remissions. Prospective, controlled trials are warranted.