R/R MM: HDAC inhibitor achieves response in combination with bortezomib and dexamethasone

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Takeaway

  • Ricolinostat 160 mg/d in combination with bortezomib and dexamethasone was well tolerated and delivered promising efficacy in patients with relapsed/refractory (R/R) multiple myeloma (MM).

Why this matters

  • Resistance to proteasome inhibition is inevitable leading to disease progression.
  • Ricolinostat is a selective histone deacetylase (HDAC6) inhibitor which may offer anti-myeloma efficacy in combination with proteasome inhibition.

Study design

  • Phase 1/2 study to investigate ricolinostat in 72 patients with R/R MM.
  • Patients were assigned to 5 ricolinostat monotherapy cohorts and 9 dose cohorts in combination with bortezomib and dexamethasone.
  • Funding: Acetylon Pharmaceuticals, Inc.

Key results

  • No patients achieved response with ricolinostat monotherapy.
  • Overall 29% response with combination therapy; 39% clinical benefit rate.
  • The greatest response (37%) and clinical benefit rate (53%) was observed at 6 mo in patients receiving ricolinostat 160 or 240 mg daily as part of the combination regimen.
  • 17% overall response in bortezomib-refractory patients receiving combination therapy.
  • 20% response in bortezomib-refractory patients receiving ricolinostat 160 mg twice-daily as part of the combination regimen.
  • Most common adverse events with combination therapy: thrombocytopenia (71%), diarrhea (67%), anemia (42%), fatigue (42%), nausea (38%).

Limitations

  •  Limited sample size for each dose cohort.