Aplidin^® (Plitidepsin) Activity In Peripheral T-Cell Lymphoma (PTCL): Final Results

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.

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).

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.

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.

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