Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010

Abstract

The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy results in significant improvement in clinical outcome for individuals with non-HIVassociated aggressive B-cell lymphoma. To assess the potential risks and benefits of the addition of rituximab to CHOP for HIV-associated non-Hodgkin lymphoma (HIV-NHL) 150 patients receiving CHOP for HIV-NHL were randomized (2:1) to receive 375 mg/m 2 rituximab with each chemotherapy cycle (n ‫؍‬ 99) or no immunotherapy (n ‫؍‬ 50) in a multicenter phase 3 trial. The complete response rate (CR ؉ CRu) was 57.6% for R-CHOP and 47% for CHOP (P ‫؍‬ .147). With a median follow-up of 137 weeks, time to progression, progression-free survival, and overall survival times were 125, 45, and 139 weeks, respectively, for R-CHOP and 85, 38, and 110 weeks, respectively, for CHOP (P ‫؍‬ not significant, all comparisons). Treatment-related infectious deaths occurred in 14% of patients receiving R-CHOP compared with 2% in the chemotherapy-alone group (P ‫؍‬ .035). Of these deaths, 60% occurred in patients with CD4 counts less than 50/mm 3 . Progression-free survival was significantly influenced by CD4 ؉ count (P < .001) and International Prognostic Index score (P ‫؍‬ .022), but not bcl-2 status. The addition of rituximab to CHOP in patients with HIV-NHL may be associated with improved tumor responses. However, these benefits may be offset by an increase in infectious deaths, particularly in those individuals with CD4 ؉ lymphocyte counts less than 50/mm 3 .

Burkitt lymphoma in adults

“…A corollary of the association of BL with relative high CD4 counts is that the introduction of effective anti-retroviral therapy has not reduced the incidence of BL as it has for other types of AIDS-related lymphomas (Biggar et al, 2007). Until recently it was thought that the severely immunocompromised patient could not tolerate the intensive chemotherapy regimens used in sporadic BL, this view was supported by the finding of a worse outcome associated with rituximab (+CHOP) in a randomized trial for patients with AIDS-related lymphomas (Kaplan et al, 2005). This view no longer predominates, and almost all centres advocate aggressive short duration regimens although some still withhold rituximab (Perkins & Friedberg, 2008).…”

Rituximab therapy in malignant lymphoma

“…The only yet reported randomized study without benefit in the rituximab arm was in patients with human immunodeficiency virus -associated lymphoma: the RR was not statistically different in R-CHOP or CHOP arms (Kaplan and Scadden (2004)). However, this study did not have the power to show a significant difference and the follow-up is extremely short.…”

AIDS and associated malignancies

“…These patients had favorable prognostic factors (median CD4+ lymphocyte count of 233 mm 3 /ml) [20]. Enhanced toxicity of rituximab and CHOP chemotherapy was recently noted in a large multi-center trial conducted by the AMC [22]. The addition of rituximab to standard-dose CHOP as compared to CHOP alone led to increased infectious complications and deaths attributable to sepsis.…”