Adding Rituximab to CHOP for HIV-Lymphoma: Do the Benefits Outweigh the Risks?
Abstract & Commentary
By William B. Ershler, MD, Editor, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.
Synopsis: Patients with HIV-associated non-Hodgkin's lymphoma have been successfully treated with chemotherapy since the advent of more effective anti-retroviral combinations. The question remains whether the additional value of rituximab to the CHOP combination would be countered by its immunosuppressive effects and risk of infection. In the current phase II trial from France, 61 patients with HIV-NHL were treated with R-CHOP and the results in terms of complete response rate and survival are quite encouraging. However, the patients included in this trial did not have advanced AIDS or low CD4 counts and, thus, the current findings do not reflect the full spectrum of HIV-NHL and should not be generalized with regard to treatment recommendations.
Source: Boue F, et al. Phase II trial of CHOP plus rituximab in patients with HIV-associated non-Hodgkin's lymphoma. J Clin Oncol. 2006;24:4123-4128.
Prior to the advent of highly active antiretroviral therapy (HAART) the occurrence of non-Hodgkin's lymphoma (NHL) was a strongly negative prognostic factor and lymphoma treatment success was unusual. For example, in various clinical trials the median survival was 8 months and only 10% survived two years after lymphoma onset.1 However, since the occurrence of HAART, prognosis for HIV-NHL patients has improved considerably.2 The current study was undertaken in 1998 in a French multicenter trial to address the concern whether the addition of the monoclonal anti-CD20 rituximab would, due to its immunosuppressive effects, adversely affect clinical outcomes for HIV patients with NHL.
HIV-seropositive patients with high-grade lymphoma of B-cell origin were eligible if their CD4 cell count was > 100/ L, they were without prior history of opportunistic infection and were of reasonably good performance status (ECOG, 0-2). All of the enrolled patients (n = 61) were evaluable with regard to safety and in 52 tumor responses could be assessed. The median age was 41 years and the median CD4 count was 172/L. The histologic types included diffuse large B-cell lymphoma (n = 42), immunoblastic (n = 2), Burkitt lymphoma (n = 16) and plasmablastic (n = 1). Forty-two patients had stage III/IV disease and the International Prognostic Index (IPI) was 0 to 1 in 31 patients and 2 to 3 in 27 patients. Rituximab was administered at a dose of 375 mg/m2 followed (next day) by CHOP (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 [maximum 2 mg], and prednisone 40 mg/m2 orally for 5 days).
Grade 3 or 4 toxicity consisted of febrile neutropenia in 9 patients, anemia in 16 patients, and thrombocytopenia in 5 patients. Complete remission (CR) was achieved in 40 of the 52 assessable patients, partial remission in 5 patients and disease progression in 7 patients. At a median of 33 months, 43 patients were alive and the estimated 2-year overall survival rate was 75% (95% CI, 64%-86%). In the 18 patients who had died, lymphoma was the primary cause in 16, HIV encephalitis in 1 and infection in 1.
Thus, the authors concluded that rituximab could be safely added to CHOP chemotherapy for selected patients with HIV-associated NHL in an effort to optimize response rate and overall survival.
In this Phase II study, rituximab added to the standard CHOP regimen produced quite favorable results (77% CR rate, 75% two-year survival), numbers that are most encouraging in this setting. Yet, the numbers are in stark contrast to that from the AIDS-Malignancies Consortium trial (AMC 010).3 In that randomized trial, there were 16 infection-related deaths and 15 of these occurred in the rituximab arm. However, in the AMC trial patients with more advanced HIV infection were included, whereas the current trial excluded patients who, at the time of enrollment, had CD4 counts < 100/L and any history of opportunistic infection.
Accordingly, this report adds significant positive information with regard to which HIV-NHL patients can be safely treated with R-CHOP. The data suggest for HIV patients with good performance status and CD4 counts above 100/L, rituximab can be safely used in lymphoma treatment schemas. For patients with active AIDS, low CD4 counts or poor performance status, reservations regarding rituximab use would still seem appropriate.
1. Kaplan LD, et al. Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med. 1997;336:1641-1648.
2. Besson C, et al. Changes in AIDS-related lymphoma since the era of highly active antiretroviral therapy. Blood. 2001;98:2339-2344.
3. Kaplan LD, et al. 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. Blood. 2005;106:1538-1543.