Tolerability to romidepsin in patients with relapsed/refractory T-cell lymphoma

Biomarker Research

Francine Foss⁶  Bertrand Coiffier¹⁴  Steven Horwitz¹²  Barbara Pro²  H Miles Prince¹³  Lubomir Sokol¹¹  Matthew Greenwood⁷  Adam Lerner¹⁰  Dolores Caballero¹  Eugeniusz Baran⁵  Ellen Kim⁹  Jean Nichols⁴  Barbara Balser³  Julie Wolfson³  Sean Whittaker⁸ 

[1] Hospital Universitario de Salamanca, Salamanca, Spain

[2] Thomas Jefferson University, Philadelphia, PA, USA

[3] Veristat, LLC, Holliston, MA, USA

[4] J Nichols LLC, Swampscott, MA, USA

[5] Wroclaw Medical University, Wroclaw, Poland

[6] Yale Cancer Center, PO Box 208028, 333 Cedar Street, TMP 3, New Haven, CT 06520-8028, USA

[7] Royal North Shore Hospital, Sydney, New South Wales, Australia

[8] Guy’s and St Thomas’ Hospital, London, England, United Kingdom

[9] University of Pennsylvania, Philadelphia, PA, USA

[10] Boston Medical Center, Boston, MA, USA

[11] Moffitt Cancer Center, Tampa, FL, USA

[12] Memorial Sloan Kettering Cancer Center, New York, NY, USA

[13] Peter MacCallum Cancer Centre and University of Melbourne, East Melbourne, Victoria, Australia

[14] Hospices Civils de Lyon, Lyon, France

关键词: Discontinuations;    Adverse events;    PTCL;    CTCL;    Romidepsin;   

Others  :  1084172
DOI  :  10.1186/2050-7771-2-16

 received in 2014-06-25, accepted in 2014-06-27,  发布年份 2014

【 摘 要 】

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/m² 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.

Trial registration

NCT00426764,NCT00106431

【 授权许可】

   
2014 Foss et al.; licensee BioMed Central Ltd.

【 图 表 】

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