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

✍ Scribed by David T. Scadden; David P. Schenkein; Zale Bernstein; Barry Luskey; John Doweiko; Anil Tulpule; Alexandra M. Levine

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 101 KB
• Volume: 83
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/(sici)1097-0142(19981215)83:12<2580::aid-cncr25>3.0.co;2-c

✦ Synopsis

The objective of this study was to develop and test a combined therapeutic approach for patients with AIDS-related lymphoma (ARL), employing agents with independent mechanisms of action and nonoverlapping toxicity. This study was designed to test the feasibility and tolerance of combining low dose chemotherapy with infusional immunotoxin in the treatment of ARL patients.

METHODS. Previously

untreated patients received low dose methotrexate, bleomycin, 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 linked to modified ricin, 20 g/kg/day for 7 days administered by continuous infusion on an outpatient basis. A repeat cycle of anti-B4-bR was administered during Cycle 4 of chemotherapy based on tolerance. Patients received two cycles of chemotherapy beyond complete remission up to eight cycles. Study 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-B4-bR infusion was associated with transaminase elevation (Grade 3) in 14 of 26 patients (58%), and flulike symptoms were common. HAMA or HARA was observed in 8 patients (31%). The overall response rate was 57% (13 complete responses and 12 partial responses). The median survival for all patients was 8.9 months.

CONCLUSIONS.

This study demonstrates the safety and feasibility of using chemotherapy and immunotoxin therapies in combination and supports their further evaluation to improve the outcomes of patients with ARL.