ABSTRACT
Limited comparative data exist for the treatment of HIV-associated non-Hodgkin lymphoma. We analyzed pooled individual patient data for 1546 patients from 19 prospective clinical trials to assess treatment-specific factors (type of chemotherapy, rituximab, and concurrent combination antiretroviral [cART] use) and their influence on the outcomes complete response (CR), progression free survival (PFS), and overall survival (OS). In our analysis, rituximab was associated with a higher CR rate (odds ratio [OR] 2.89; P < .001), improved PFS (hazard ratio [HR] 0.50; P < .001), and OS (HR 0.51; P < .0001). Compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), initial therapy with more dose-intense regimens resulted in better CR rates (ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisolone]: OR 1.70; P < .04), PFS (ACVBP: HR 0.72; P = .049; "intensive regimens": HR 0.35; P < .001) and OS ("intensive regimens": HR 0.54; P < .001). Infusional etoposide, prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide (EPOCH) was associated with significantly better OS in diffuse large B-cell lymphoma (HR 0.33; P = .03). Concurrent use of cART was associated with improved CR rates (OR 1.89; P = .005) and trended toward improved OS (HR 0.78; P = .07). These findings provide supporting evidence for current patterns of care where definitive evidence is unavailable.
Subject(s)
Anti-HIV Agents/therapeutic use , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , HIV Infections/drug therapy , Lymphoma, AIDS-Related/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , Antiretroviral Therapy, Highly Active , Clinical Trials as Topic , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Drug Administration Schedule , Etoposide/therapeutic use , HIV/drug effects , HIV Infections/complications , HIV Infections/mortality , HIV Infections/virology , Humans , Infusions, Intravenous , Lymphoma, AIDS-Related/complications , Lymphoma, AIDS-Related/mortality , Lymphoma, AIDS-Related/virology , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/virology , Prednisone/therapeutic use , Rituximab , Survival Analysis , Treatment Outcome , Vincristine/therapeutic useABSTRACT
BACKGROUND: Highly active antiretroviral therapy (HAART) has improved the survival of patients with acquired immunodeficiency syndrome-related lymphoma (ARL). The German ARL Study Group investigated whether HAART administered concomitantly with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy compromised the course of immune parameters during and after chemotherapy and exerted a positive effect on remission and survival. METHODS: From 1997 to 2001, 72 patients with ARL were stratified prospectively into a standard-risk group (n = 48 patients) and a high-risk group (n = 24 patients) with either 0-1 or 2-3 of the following risk factors: CD4 < 50/microL, prior opportunistic infection, and/or a World Health Organization performance status > or = 3. Patients in the high-risk group received > or =75% of the CHOP regimen. RESULTS: In the standard-risk group (CD4 = 223/muL; age-adjusted International Prognostic Index [aaIPI], 38% > or = 2), the complete remission (CR) rate was 79%, and median survival was not reached after a median 47 months of follow-up. CD4 counts did not change from baseline to 4 weeks after the end of chemotherapy (206/microL). In the high-risk group (CD4 = 34/muL; aaIPI, 88% > or = 2), the CR rate was 29%, and the median survival was 7.2 months (3 patients survived for > 3 yrs). Toxicity was moderate: Leukopenia Grade 3 or 4 occurred in 100 of 249 chemotherapy cycles (40%) in the standard-risk group and in 70 of 102 cycles (69%) in the high-risk group. CONCLUSIONS: Based on the aaIPI, the survival of patients in the standard-risk group was very similar to that achieved by nonhuman immunodeficiency virus-infected patients who had aggressive lymphomas. Concurrent CHOP plus HAART can be administered in an outpatient setting. Thus, the authors recommend using this modality as first-line therapy for patients with ARL.
Subject(s)
Acquired Immunodeficiency Syndrome/complications , Anti-Retroviral Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antiretroviral Therapy, Highly Active , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/virology , Administration, Oral , Adult , Age Factors , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Humans , Infusions, Intravenous , Male , Prednisone/administration & dosage , Prospective Studies , Risk Factors , Survival Analysis , Vincristine/administration & dosageABSTRACT
Recently, the median survival of patients with AIDS-related lymphoma has changed significantly. This effect is mainly because of changes in the use of antiviral (highly active antiretroviral therapy; HAART) or chemotherapy regimens. Several novel treatment options have been explored in patients with lymphoma. It is hoped that innovative strategies will lead to a survival benefit in these patients. In this review, we present an update of current strategies for the treatment of AIDS-related lymphoma.
