Impact of Myc in HIV-associated non-Hodgkin lymphomas treated with EPOCH and outcomes with vorinostat (AMC-075 trial)

Juan C. Ramos, Joseph A. Sparano, Amy Chadburn, Erin G. Reid, Richard F. Ambinder, Eric R. Siegel, Page C. Moore, Paul G. Rubinstein, Christine M. Durand, Ethel Cesarman, David Aboulafia, Robert Baiocchi, Lee Ratner, Lawrence Kaplan, Adam A. Capoferri, Jeannette Y. Lee, Ronald Mitsuyasu, Ariela Noy

Research output: Contribution to journalArticle

Abstract

EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) is a preferred regimen for HIV-non-Hodgkin lymphomas (HIV-NHLs), which are frequently Epstein-Barr virus (EBV) positive or human herpesvirus type-8 (HHV-8) positive. The histone deacetylase (HDAC) inhibitor vorinostat disrupts EBV/HHV-8 latency, enhances chemotherapy-induced cell death, and may clear HIV reservoirs. We performed a randomized phase 2 study in 90 patients (45 per study arm) with aggressive HIV-NHLs, using dose-adjusted EPOCH (plus rituximab if CD20+), alone or with 300 mg vorinostat, administered on days 1 to 5 of each cycle. Up to 1 prior cycle of systemic chemotherapy was allowed. The primary end point was complete response (CR). In 86 evaluable patients with diffuse large B-cell lymphoma (DLBCL; n = 61), plasmablastic lymphoma (n = 15), primary effusion lymphoma (n = 7), unclassifiable B-cell NHL (n = 2), and Burkitt lymphoma (n = 1), CR rates were 74% vs 68% for EPOCH vs EPOCH-vorinostat (P = .72). Patients with a CD4+ count <200 cells/mm3 had a lower CR rate. EPOCH-vorinostat did not eliminate HIV reservoirs, resulted in more frequent grade 4 neutropenia and thrombocytopenia, and did not affect survival. Overall, patients with Myc+ DLBCL had a significantly lower EFS. A low diagnosis-to-treatment interval (DTI) was also associated with inferior outcomes, whereas preprotocol therapy had no negative impact. In summary, EPOCH had broad efficacy against highly aggressive HIV-NHLs, whereas vorinostat had no benefit; patients with Myc-driven DLBCL, low CD4, and low DTI had less favorable outcomes. Permitting preprotocol therapy facilitated accruals without compromising outcomes. This trial was registered at www.clinicaltrials.gov as #NCT0119384.

Original languageEnglish (US)
Pages (from-to)1284-1297
Number of pages14
JournalBlood
Volume136
Issue number11
DOIs
StatePublished - Sep 10 2020

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Impact of Myc in HIV-associated non-Hodgkin lymphomas treated with EPOCH and outcomes with vorinostat (AMC-075 trial)'. Together they form a unique fingerprint.

  • Cite this

    Ramos, J. C., Sparano, J. A., Chadburn, A., Reid, E. G., Ambinder, R. F., Siegel, E. R., Moore, P. C., Rubinstein, P. G., Durand, C. M., Cesarman, E., Aboulafia, D., Baiocchi, R., Ratner, L., Kaplan, L., Capoferri, A. A., Lee, J. Y., Mitsuyasu, R., & Noy, A. (2020). Impact of Myc in HIV-associated non-Hodgkin lymphomas treated with EPOCH and outcomes with vorinostat (AMC-075 trial). Blood, 136(11), 1284-1297. https://doi.org/10.1182/blood.2019003959