title: Tolerability to romidepsin in patients with relapsed/refractory T-cell lymphoma.
abstract: BACKGROUND
  Histone deacetylase inhibitor romidepsin has demonstrated durable clinical responses and tolerability in patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma (PTCL, CTCL). Selection of novel drug therapies for patients with relapsed/refractory aggressive lymphoma requires not only considerations regarding efficacy but also careful evaluation of toxicities as well as overall clinical benefit. The purpose of this analysis was to examine common adverse events (AEs) reported in pivotal trials of romidepsin in relapsed/refractory PTCL or CTCL and to more clearly define the overall AE profile in these populations.
  
  
  METHODS
  Patients with relapsed/refractory PTCL or CTCL were treated with romidepsin at 14 mg/m(2) as a 4-hour intravenous infusion on days 1, 8, and 15 of 28-day cycles for up to 6 cycles; patients with at least stable disease could extend therapy until progressive disease or another withdrawal criterion was met. All enrolled patients who received ≥ 1 dose of romidepsin were included in the AE analyses.
  
  
  RESULTS
  Overall, safety profiles of common AEs were similar, although patients with relapsed/refractory PTCL had more frequent hematologic toxicities and grade ≥ 3 infections. In both patient populations, the greatest incidence of grade ≥ 3 AEs and the majority of discontinuations due to AEs occurred during cycles 1-2. Early discontinuations were primarily related to infection, thrombocytopenia, or electrocardiogram abnormalities, confirming the need to closely monitor patients with poor bone marrow reserve or other comorbidities. Despite this, 28% of patients with relapsed/refractory PTCL and 36% of patients with relapsed/refractory CTCL continued on romidepsin treatment for ≥ 6 cycles.
  
  
  CONCLUSIONS
  This study demonstrates that patients with relapsed/refractory PTCL or CTCL have similar AE profiles with romidepsin treatment, although patients with PTCL experienced more frequent and more severe hematologic toxicities and more frequent grade ≥ 3 infections. The greatest incidence of grade ≥ 3 AEs and the majority of discontinuations due to AEs occurred during treatment cycles 1-2. Extended dosing of romidepsin can be tolerated in responding patients.
  
  
  BACKGROUND
  NCT00426764,NCT00106431.
authors.affiliation: Yale Cancer Center, PO Box 208028, 333 Cedar Street, TMP 3, New Haven, CT 06520-8028, USA.
authors.forename: Francine
authors.initials: F
authors.lastname: Foss
authors.affiliation: Hospices Civils de Lyon, Lyon, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coiffier
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Horwitz
authors.affiliation: Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pro
authors.affiliation: Peter MacCallum Cancer Centre and University of Melbourne, East Melbourne, Victoria, Australia.
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
authors.affiliation: Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Lubomir
authors.initials: L
authors.lastname: Sokol
authors.affiliation: Royal North Shore Hospital, Sydney, New South Wales, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Greenwood
authors.affiliation: Boston Medical Center, Boston, MA, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Lerner
authors.affiliation: Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Caballero
authors.affiliation: Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Eugeniusz
authors.initials: E
authors.lastname: Baran
authors.affiliation: University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Kim
authors.affiliation: J Nichols LLC, Swampscott, MA, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Nichols
authors.affiliation: Veristat, LLC, Holliston, MA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Balser
authors.affiliation: Veristat, LLC, Holliston, MA, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Wolfson
authors.affiliation: Guy's and St Thomas' Hospital, London, England, United Kingdom.
authors.forename: Sean
authors.initials: S
authors.lastname: Whittaker
keywords: Adverse events; CTCL; Discontinuations; PTCL; Romidepsin