Affiliation:
1. Institut Gustave Roussy, Villejuif, France,
2. Hospital Universitario de Salamanca, Salamanca, Spain,
3. Clinical Oncology, PharmaMar SAU, Colmenar Viejo, Spain,
4. Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland,
5. Istituto Nazionale Tumori, Milano, Italy
Abstract
Abstract
Abstract 1767
Background:
Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of NHL, representing 10–15% of all newly diagnosed cases; their prognosis is poor and optimal therapy is yet to be defined. Most patients (pts) relapse after standard first-line chemotherapy and ultimately die from their disease. Though pralatrexate has been recently FDA-approved for this indication, novel active agents are still needed. From December 2004 to June 2008, 46 adult pts with aggressive non-Hodgkin lymphoma (NHL) were treated in a phase II study aimed at evaluating the activity of plitidepsin. An interim analysis showed responses restricted to pts with PTCL (4/17 vs. 0/29 in pts with B-cell NHL; Fisher's test: p=0.01). Thus, PTCL cohort was expanded. Herein, final results are presented.
Patients and methods:
As of June 2010, 32 pts were treated with plitidepsin 3.2 mg/m2 i.v. infusion over 1-h on days 1, 8 and 15 q4wk. Twenty-nine pts are evaluable for efficacy. Median number of previous regimens was 2 (range, 1–6), including prior stem cell transplantation in 9 pts (28%). Histology: PTCL, NOS 16, anaplastic large-cell 4, angioimmunoblastic 9 and NK/T nasal type 3. Twenty-three pts were male, median age was 57 y (30-80) and ECOG: 0 (14 pts), 1 (12 pts) and 2 (6 pts).
Results:
Two CR and 4 PR were observed, for a 20% objective response rate (95% CI, 8%-39%). Median duration of response was 2.2 months (range, 1 – 28). Median progression-free survival was 1.6 months (95% CI, 1 – 3) and median overall survival was 10.2 months (95% CI, 4 – 24). Toxicity, particularly haematological, was mild. Two patients developed G3, and 2 G4 neutropenia, and 1 pt G3, and 2 G4 thrombocytopenia. Transient and reversible G3 ALT or AST elevations occurred in 7 and 4 pts, respectively, with no patients experiencing G4 events. Clinical toxicities were mainly G1-2 muscular weakness and myalgia in 14% of pts, and G1-2 fatigue, nausea and vomiting in 21%, 28% and 17% of patients, respectively.
Conclusions:
Plitidepsin has activity, with an acceptable safety profile in non-cutaneous relapsed/refractory PTCL patients. Remarkably, lack of hematologic toxicity makes plitidepsin an ideal agent either for treating patients with poor bone marrow reserve or combining it with other active agents. A combination of plitidepsin with gemcitabine is currently being explored in this patient population.
Disclosures:
Szyldergemajn: PharmaMar SAU: Employment. Corrado:PharmaMar SAU: Employment. Extremera:PharmaMar SAU: Employment. Vandermeeren:PharmaMar SAU: Employment.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Cited by
3 articles.
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