Romidepsin in peripheral and cutaneous T-cell lymphoma: mechanistic implications from clinical and correlative data

TY - JOUR

T1 - Romidepsin in peripheral and cutaneous T-cell lymphoma

T2 - mechanistic implications from clinical and correlative data

AU - Bates, Susan E

AU - Eisch, Robin

AU - Ling, Alexander

AU - Rosing, Douglas

AU - Turner, Maria

AU - Pittaluga, Stefania

AU - Prince, H Miles

AU - Kirschbaum, Mark H

AU - Allen, Steven L

AU - Zain, Jasmine

AU - Geskin, Larisa J

AU - Joske, David

AU - Popplewell, Leslie

AU - Cowen, Edward W

AU - Jaffe, Elaine S

AU - Nichols, Jean

AU - Kennedy, Sally

AU - Steinberg, Seth M

AU - Liewehr, David J

AU - Showe, Louise C

AU - Steakley, Caryn

AU - Wright, John

AU - Fojo, Tito

AU - Litman, Thomas

AU - Piekarz, Richard L

N1 - © 2015 John Wiley & Sons Ltd.

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Romidepsin is an epigenetic agent approved for the treatment of patients with cutaneous or peripheral T-cell lymphoma (CTCL and PTCL). Here we report data in all patients treated on the National Cancer Institute 1312 trial, demonstrating long-term disease control and the ability to retreat patients relapsing off-therapy. In all, 84 patients with CTCL and 47 with PTCL were enrolled. Responses occurred early, were clinically meaningful and of very long duration in some cases. Notably, patients with PTCL receiving romidepsin as third-line therapy or later had a comparable response rate (32%) of similar duration as the total population (38%). Eight patients had treatment breaks of 3.5 months to 10 years; in four of six patients, re-initiation of treatment led to clear benefit. Safety data show slightly greater haematological and constitutional toxicity in PTCL. cDNA microarray studies show unique individual gene expression profiles, minimal overlap between patients, and both induction and repression of gene expression that reversed within 24 h. These data argue against cell death occurring as a result of an epigenetics-mediated gene induction programme. Together this work supports the safety and activity of romidepsin in T-cell lymphoma, but suggests a complex mechanism of action.

AB - Romidepsin is an epigenetic agent approved for the treatment of patients with cutaneous or peripheral T-cell lymphoma (CTCL and PTCL). Here we report data in all patients treated on the National Cancer Institute 1312 trial, demonstrating long-term disease control and the ability to retreat patients relapsing off-therapy. In all, 84 patients with CTCL and 47 with PTCL were enrolled. Responses occurred early, were clinically meaningful and of very long duration in some cases. Notably, patients with PTCL receiving romidepsin as third-line therapy or later had a comparable response rate (32%) of similar duration as the total population (38%). Eight patients had treatment breaks of 3.5 months to 10 years; in four of six patients, re-initiation of treatment led to clear benefit. Safety data show slightly greater haematological and constitutional toxicity in PTCL. cDNA microarray studies show unique individual gene expression profiles, minimal overlap between patients, and both induction and repression of gene expression that reversed within 24 h. These data argue against cell death occurring as a result of an epigenetics-mediated gene induction programme. Together this work supports the safety and activity of romidepsin in T-cell lymphoma, but suggests a complex mechanism of action.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibiotics, Antineoplastic/adverse effects

KW - Depsipeptides/adverse effects

KW - Epigenomics

KW - Female

KW - Histone Deacetylase Inhibitors/adverse effects

KW - Humans

KW - Lymphoma, T-Cell, Cutaneous/drug therapy

KW - Male

KW - Middle Aged

KW - Prospective Studies

KW - Skin Neoplasms/drug therapy

U2 - 10.1111/bjh.13400

DO - 10.1111/bjh.13400

M3 - Journal article

C2 - 25891346

SN - 0007-1048

VL - 170

SP - 96

EP - 109

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 1

ER -