Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma

BACKGROUND: Improved outcomes have recently been reported for rituximab (R) plus rituximab plus infusional etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) chemotherapy in patients with human immunodeficiency virus (HIV)-associated, aggressive B-cell, non-Hodgkin lymphoma (NHL). The objective of the current analysis was to assess whether patient selection or other factors contributed to this improvement and to identify patients who are at the greatest risk for lethal toxicity. METHODS: The authors performed a pooled analysis of 2 consecutive trials that included 150 patients with HIV-associated NHL who received either R-CHOP (n = 99; Acquired Immunodeficiency Syndrome [AIDS] Malignancy Consortium Trial 010 [AMC010]) or R-EPOCH (n = 51; AMC034). Age-adjusted International Prognostic Index (aaIPI), CD4 count at lymphoma diagnosis (<100/μL vs ≥100/μL), and treatment (R-CHOP vs R-EPOCH) were included as variables in a multivariate logistic regression model for complete response (CR) and in a Cox proportional hazards regression models for event-free survival (EFS) and overall survival (OS). RESULTS: Features that were associated significantly with an improved CR rate and improved EFS and OS included a low aaIPI score and a baseline CD4 count ≥100/μL. When the analysis was adjusted for aaIPI and CD4 count, patients who received concurrent R-EPOCH had improved EFS (hazard ratio [HR] 0.40; 95% confidence intervals [CI], 0.23, 0.69; P <.001) and OS (HR, 0.38; 95% CI, 0.21, 0.69; P <.01). Treatment-associated death occurred significantly more often in patients with CD4 counts <50/μL (37% vs 6%; P <.01). CONCLUSIONS: The current analysis provided additional level 2 evidence supporting the use of concurrent R-EPOCH in patients with HIV-associated lymphoma and a CD4 count >50/μL, and the results support the design of an ongoing phase 3 trial comparing concurrent R-EPOCH with R-CHOP in immunocompetent patients with diffuse large B-cell lymphoma (National Clinical Trial no. NCT00118209). Cancer 2012. © 2011 American Cancer Society. Clinical outcomes improve for patients with human immunodeficiency virus-associated lymphoma who receive concurrent rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin compared with patients who receive rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone when the analyses are adjusted for other covariates in a pooled analysis that includes 2 consecutive clinical trials. In addition, treatment-associated deaths occur significantly more often in patients who have baseline CD4 counts <50/μL irrespective of therapy.