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

Stefan K. Barta, Jeannette Y. Lee, Lawrence D. Kaplan, Ariela Noy, Joseph A. Sparano

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)3977-3983
Number of pages7
JournalCancer
Volume118
Issue number16
DOIs
StatePublished - Aug 15 2012

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Non-Hodgkin's Lymphoma
Acquired Immunodeficiency Syndrome
HIV
Drug Therapy
Vincristine
Prednisone
Neoplasms
Doxorubicin
Cyclophosphamide
Etoposide
CD4 Lymphocyte Count
Lymphoma
Clinical Trials
Lymphoma, Large B-Cell, Diffuse
Rituximab
Patient Selection
B-Lymphocytes
Therapeutics

Keywords

  • acquired immunodeficiency syndrome
  • acquired immunodeficiency syndrome-related
  • antineoplastic agents
  • B-cell lymphoma
  • Burkitt lymphoma
  • drug therapy
  • human immunodeficiency virus
  • immunoblastic
  • large-cell
  • lymphoma
  • murine-derived monoclonal antibodies
  • non-Hodgkin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma. / Barta, Stefan K.; Lee, Jeannette Y.; Kaplan, Lawrence D.; Noy, Ariela; Sparano, Joseph A.

In: Cancer, Vol. 118, No. 16, 15.08.2012, p. 3977-3983.

Research output: Contribution to journalArticle

Barta, Stefan K. ; Lee, Jeannette Y. ; Kaplan, Lawrence D. ; Noy, Ariela ; Sparano, Joseph A. / Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma. In: Cancer. 2012 ; Vol. 118, No. 16. pp. 3977-3983.
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abstract = "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. {\circledC} 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.",
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journal = "Cancer",
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TY - JOUR

T1 - Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma

AU - Barta, Stefan K.

AU - Lee, Jeannette Y.

AU - Kaplan, Lawrence D.

AU - Noy, Ariela

AU - Sparano, Joseph A.

PY - 2012/8/15

Y1 - 2012/8/15

N2 - 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.

AB - 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.

KW - acquired immunodeficiency syndrome

KW - acquired immunodeficiency syndrome-related

KW - antineoplastic agents

KW - B-cell lymphoma

KW - Burkitt lymphoma

KW - drug therapy

KW - human immunodeficiency virus

KW - immunoblastic

KW - large-cell

KW - lymphoma

KW - murine-derived monoclonal antibodies

KW - non-Hodgkin

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DO - 10.1002/cncr.26723

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