A phase II trial of pegylated doxorubicin, rituximab, cyclophosphamide, vincristine, and prednisone (DR-COP) in patients with newly diagnosed AIDS-associated B-cell non-Hodgkin's lymphoma (ARL): An AIDS Malignancy Consortium trial (AMC 047).

Abstract

8034 Background: Previous studies of CHOP have shown some efficacy in patients with ARL; addition of rituximab has improved response. Response might be limited by MDR-1 resistance, reported in 66% at diagnosis (Leuk Res 2002: 26: 121-7). Infusional regimens such as (R)- EPOCH (Blood 2003:101: 4653-59) may overcome MDR-1, and have shown superior results, but phase III studies of CHOP- vs EPOCH have not been performed in HIV patients. Substitution of doxorubicin for pegylated doxorubicin may overcome MDR-1, and DR-COP would be easier to administer than a 96 hour EPOCH infusion. We wished to determine response rates, duration, median survival and infections after DR-COP. Methods: All patients received pegylated doxorubicin 40 mg/m2, rituximab 375 mg/m2, cyclophosphamide 750 mg/m2 and vincristine 1.4 mg/m2 (2 mg) IV on day 1, with prednisone, 100 mg daily × 5 days, every 21- 28 days for 6-8 cycles depending on interim response. Restaging was performed after cycles 2, 4 and 6. Anti-retroviral therapy was given to all. Results: 43 patients were enrolled; 2 withdrew prior to receiving therapy. Median age was 44 years (21-68); 10 were female. Major risk factors for HIV were homosexual/bisexual (41%), and heterosexual contact (39%). Median CD4 cell count at entry was 119 (5 - 1026); median HIV viral load was 27,175 copies/ml (undetectable to > 9 million). Stage IV was present in 56%. Diffuse large B-cell lymphoma was diagnosed in 98%. 46% completed treatment per protocol, 27% terminated early for disease progression, and 12% terminated early for adverse event. Complete remission was documented in 15 (37%); PR in 8 (20%). Twelve patients have died (29%), due to lymphoma in 11, and progressive multifocal leukoencephalopathy (PML) in 1. The overall survival at one year is 67% (95% CI, 47%, 81%). Conclusions: Preliminary results of the DR-COP regimen do not indicate equivalent efficacy to EPOCH based regimens in ARL. Only one patient died of infection (PML), despite use of rituximab. Future studies should build upon the EPOCH backbone in patients with ARL. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NCI