Phase II trial of single-agent panobinostat consolidation improves responses after sub-optimal transplant outcomes in multiple myeloma

Br J Haematol. 2021 Apr;193(1):160-170. doi: 10.1111/bjh.17080. Epub 2020 Sep 18.


Panobinostat is a pan-deacetylase inhibitor that modulates the expression of oncogenic and immune-mediating genes involved in tumour cell growth and survival. We evaluated panobinostat-induced post-transplant responses and identified correlative biomarkers in patients with multiple myeloma who had failed to achieve a complete response after autologous transplantation. Patients received panobinostat 45 mg administered three-times weekly (TIW) on alternate weeks of 28-day cycles commencing 8-12 weeks post-transplant. Twelve of 25 patients (48%) improved their depth of response after a median (range) of 4·3 (1·9-9·7) months of panobinostat. In responders, T-lymphocyte histone acetylation increased after both three cycles (P < 0·05) and six cycles (P < 0·01) of panobinostat when compared to baseline, with no differences in non-responders. The reduction in the proportion of CD127+ CD8+ T cells and CD4:CD8 ratio was significantly greater, after three and six cycles of panobinostat compared to pre-transplant, in non-responders when compared to responders. Whole marrow RNA-seq revealed widespread transcriptional changes only in responders with baseline differences in genes involved in ribosome biogenesis, oxidative phosphorylation and metabolic pathways. This study confirmed the efficacy of panobinostat as a single agent in multiple myeloma and established acetylation of lymphocyte histones, modulation of immune subsets and transcriptional changes as pharmacodynamic biomarkers of clinical benefit.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • CD4 Antigens / drug effects
  • CD4 Antigens / immunology
  • CD8 Antigens / drug effects
  • CD8 Antigens / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / pathology
  • Female
  • Follow-Up Studies
  • Histone Deacetylase Inhibitors / administration & dosage
  • Histone Deacetylase Inhibitors / adverse effects
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Histones / drug effects
  • Histones / metabolism
  • Humans
  • Interleukin-7 Receptor alpha Subunit / drug effects
  • Interleukin-7 Receptor alpha Subunit / immunology
  • Male
  • Middle Aged
  • Multiple Myeloma / immunology
  • Multiple Myeloma / metabolism*
  • Multiple Myeloma / mortality
  • Multiple Myeloma / therapy*
  • Neoplasm Staging / methods
  • Oncogenes / drug effects
  • Panobinostat / administration & dosage
  • Panobinostat / adverse effects
  • Panobinostat / therapeutic use*
  • Remission Induction
  • Survival Analysis
  • Transplantation, Autologous / adverse effects*
  • Transplantation, Autologous / statistics & numerical data
  • Treatment Outcome


  • CD4 Antigens
  • CD8 Antigens
  • Histone Deacetylase Inhibitors
  • Histones
  • Interleukin-7 Receptor alpha Subunit
  • Panobinostat