Immunotoxin combined with chemotherapy for patients with AIDS-related non-Hodgkin's lymphoma

BACKGROUND. The objective of this study was to develop and test a combined therapeutic approach for patients with AIDS-related lymphoma (ARL), employi ng agents with independent mechanisms of action and nonoverlapping toxicity . This study was designed to test the feasibility and tolerance of combinin g low dose chemotherapy with infusional immunotoxin in the treatment of ARL patients. METHODS. Previously untreated patients received low dose methotrexate, bleo mycin, doxorubicin, cyclophosphamide, and vincristine (m-BACOD) on a 21- to 28-day schedule. Patients who did not have progressive disease by Cycle 3 received anti-B4-blocked ricin (anti-B4bR), a murine monoclonal antibody li nked to modified ricin, 20 mu g/kg/day for 7 days administered by continuou s infusion on an outpatient basis. A repeat cycle of anti-B4-bR was adminis tered during Cycle 4 of chemotherapy based on tolerance. Patients received two cycles of chemotherapy beyond complete remission up to eight cycles. St udy endpoints were toxicity, development of human antimurine antibody (HAMA ) and human antiricin (HARA), tumor response, and survival. RESULTS. Twenty-six of 44 patients received the immunotoxin therapy. Anti-B 4-bR infusion was associated with transaminase elevation (Grade 3) in 14 of 26 patients (58%), and flulike symptoms were common. HAMA or HARA was obse rved in 8 patients (31%). The overall response rate was 57% (13 complete re sponses and 12 partial responses). The median survival for all patients was 8.9 months. CONCLUSIONS. This study demonstrates the safety and feasibility of using ch emotherapy and immunotoxin therapies in combination and supports their furt her evaluation to improve the outcomes of patients with ARL. Cancer 1998;83 :2580-7. (C) 1998 American Cancer Society.