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

TitleImpact of Myc in HIV-associated non-Hodgkin lymphomas treated with EPOCH and outcomes with vorinostat (AMC-075 trial).
Publication TypeJournal Article
Year of Publication2020
AuthorsRamos JC, Sparano JA, Chadburn A, Reid EG, Ambinder RF, Siegel ER, Moore PC, Rubinstein PG, Durand CM, Cesarman E, Aboulafia D, Baiocchi R, Ratner L, Kaplan L, Capoferri AA, Lee JY, Mitsuyasu R, Noy A
Date Published2020 09 10
KeywordsAdult, Aged, Anti-HIV Agents, Antineoplastic Combined Chemotherapy Protocols, CD4 Lymphocyte Count, Cyclophosphamide, DNA, Viral, Doxorubicin, Drug Administration Schedule, Etoposide, Female, Genes, myc, Herpesviridae Infections, Herpesvirus 4, Human, Herpesvirus 8, Human, Histone Deacetylase Inhibitors, HIV Infections, HIV-1, Humans, Kaplan-Meier Estimate, Lymphoma, AIDS-Related, Lymphoma, Non-Hodgkin, Male, Middle Aged, Neutropenia, Prednisone, Progression-Free Survival, Prospective Studies, Rituximab, Thrombocytopenia, Treatment Outcome, Vincristine, Viral Load, Vorinostat

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 as #NCT0119384.

Alternate JournalBlood
PubMed ID32430507
PubMed Central IDPMC7483436
Grant ListP30 AI094189 / AI / NIAID NIH HHS / United States
UG1 CA189859 / CA / NCI NIH HHS / United States
UM1 CA181255 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
P30 CA240139 / CA / NCI NIH HHS / United States
UM1 CA121947 / CA / NCI NIH HHS / United States
U01 CA121947 / CA / NCI NIH HHS / United States
Related Faculty: 
Amy Chadburn, M.D. Ethel Cesarman, M.D., Ph.D.

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