Kim, S.J. and Kim, W.S. recently responded to the comments of Tan et al. in the Annals of Oncology about their recently published study on Epstein-Barr Virus (EBV) reactivation in Extranodal Natural Killer/T-cell Lymphoma (ENKTL) patients. Their responding commentary included:
- Supporting their original statement that romidepsin should be avoided in ENKTL patients due to EBV reactivation based upon:
- Their own phase-II study where romidepsin was a single agent
- Their in vitro studies showing EBV reactivation in ENKTL cell lines after treatment with three different HDAC inhibitors.
- Additional studies which have also shown an association between HDAC inhibitors and reactivation of EBV e.g. Tsai et al, and Lee et al.
- Agreement that in R/R ENKTL, without any other options, a combination of two or more drugs
- One PR and one CR reported by Tan et al. (2015) in R/R ENKL pts treated with panobinostat and bortezomib in a phase-II study without EBV reactivation
- Implied HDAC inhibitor + proteasome inhibitor could be possible without EBV reactivation
- Unclear how proteasome inhibitor reduces the effect of HDAC inhibition on EBV reactivation
In conclusion, Kim and Kim stated that a larger study in R/R ENKTL patients needs to be conducted to better understand whether bortezomib combined with a HDAC inhibitor, such as romidepsin, could be both effective while mitigating the effect on EBV reactivation.
- Tan, D. et al. Histone deacetylase (HDAC) inhibitors when combined with a proteasome inhibitor are safe and effective in patients with extranodal natural killer/T-cell lymphoma (ENKTL). Annals of Oncology. 2016 Jun. 27 (9): 1811-1812. doi: 10.1093/annonc/mdw231.
- Kim, S.J. and Kim, W.S. Reply to the letter to the editor ‘Epstein–Barr virus reactivation in extranodal natural killer/T-cell lymphoma patients: a previously unrecognized serious adverse event in a pilot study with romidepsin, histone deacetylase (HDAC) inhibitors when combined with a proteasome inhibitor are safe and effective in patients with extranodal natural killer/T-cell lymphoma’. Annals of Oncology. 2016 Nov. 27 (11): 2133-2134. doi: 10.1093/annonc/mdw296.
- Tsai, PF. et al. Interplay between PKCδ and Sp1 on Histone Deacetylase Inhibitor-Mediated Epstein-Barr Virus Reactivation. Journal of Virology. 2011 Mar. 85 (5): 2273-2385. doi: 10.1128/JVI.01602-10.
- Lee, HH. et al. Essential role of PKCdelta in histone deacetylase inhibitor-induced Epstein-Barr virus reactivation in nasopharyngeal carcinoma cells. Journal of General Virology. 2008 Apr. 89: 878-883. doi: 10.1099/vir.0.83533-0
- Tan, D. et al. Panobinostat in combination with bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma: an open-label, multicentre phase 2 trial. Lancet Haematology. 2015 Aug. 2(8):e326-33. doi: 10.1016/S2352-3026(15)00097-6.