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Phase II Trial of CHOP Plus Rituximab in Patients With HIV-Associated Non-Hodgkin’s Lymphoma

Division of Medical Oncology A, National Cancer Institute–Centro di Riferimento Oncologico, Aviano, Italy

To the Editor:

Recently Bouè et al¹ published the results of a French phase II trial with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in 61 patients with HIV-associated non-Hodgkin's lymphoma (HIV-NHL). They reported a complete remission rate of 77% and a 2-year survival of 75% without any increase of both toxic deaths and life-threatening infections. These results are similar to that of our pooled analysis of three international phase two studies using rituximab plus infusional cyclophosphamide, doxorucin and etoposide (R-CDE)² in 74 patients with HIV-NHL with a complete remission rate of 70% and a 2-year survival of 64%. However, a significant increase in hematologic toxicity and infections were found in the R-CDE study, in particular, grade 3 to 4 neutropenia in 78% of patients and infection in 31% of patients. These differences could be related to several factors. First, in the R-CDE study all patients were treated, while in the R-CHOP study only patients with good or intermediate prognosis (ie, no more than one of the following prognostic factors: CD4 cell count < 100/dL, prior history of opportunistic infections, and Eastern Cooperative Oncology Group performance status > 2) were enrolled. Second, due to the continuous infusion of R-CDE all patients used a central venous catheter, which is a risk factor for bacterial infections. Third, in the R-CDE study all antiretroviral drugs were allowed while in the R-CHOP study, the use of mielotoxic antiretroviral drugs, such as zidovudine or ritonavir, was avoided, leading to a low rate of grade 3 or 4 neutropenia (33% in R-CHOP v 78% in R-CDE). Last, the use of etoposide could have contributed to the increase of bone marrow toxicity.

Overall, the results of the French study confirm the results of R-CDE with a high efficacy of the addition of rituximab to chemotherapy in the treatment of patients with HIV-NHL without any overall increase in severe toxicity. These results are in contrast with the previous US data published by Kaplan et al³ where rituximab was associated to an unacceptable rate of treatment-related infectious deaths; although, the patient selection could be the reason for this toxicity. In conclusion, rituximab plus chemotherapy should be considered the standard treatment of patients with HIV-NHL. Randomized studies comparing rituximab plus CHOP versus rituximab plus infusional chemotherapy (CDE or etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin [EPOCH]) could be warranted in order to improve both response rate and overall survival.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The authors indicated no potential conflicts of interest.

ACKNOWLEDGMENTS

Supported by grants from the Istituto Superiore di Sanità and the Associazione Italiana Ricerca sul Cancro.

REFERENCES

1. Bouè F, Gabarre J, Gisselbrecht C, et al: Phase II trial of CHOP plus rituximab in patients with HIV-associated non-Hodgkin's lymphoma. J Clin Oncol 24:4123-4128, 2006[Abstract/Free Full Text]

2. Spina M, Jaeger U, Sparano JA, et al: Rituximab plus infusional cyclophosphamide, doxorucin, and etoposide in HIV-associated non-Hodgkin's lymphoma: Pooled results from 3 phase 2 trials. Blood 105:1891-1897, 2005[Abstract/Free Full Text]

3. Kaplan LD, Lee JY, Ambinder RF, 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's lymphoma: AIDS-Malignancies Consortium trial 010. Blood 106:1538-1543, 2005[Abstract/Free Full Text]

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