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Clinical Efficacy, Tolerability, and Safety of SAM486A, a Novel Polyamine Biosynthesis Inhibitor, in Patients with Relapsed or Refractory Non-Hodgkin’s Lymphoma

Results from a Phase II Multicenter Study

¹ University Hospital of Basel, Switzerland;² Hôpital Henri Mondor, Créteil, France;³ Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany;⁴ Klinikum Grosshadern, Munich, Germany;⁵ Centre Hospitalier Lyon Sud, France;⁶ Universitätsklinik Köln, Germany;⁷ Novartis Pharma AG, Basel, Switzerland;⁸ Novartis Corp., East Hanover, New Jersey; and⁹ Grace Cancer Drug Center, Roswell Park Cancer Institute, New York, New York

Purpose: SAM486A is a new inhibitor of S-adenosyl-methionine-decarboxylase, a key enzyme for polyamine biosynthesis. It is more potent than the first generation S-adenosyl-methionine-decarboxylase inhibitor methylglyoxal bis-guanylhydrazone. This Phase IIa study reports the findings of SAM486A monotherapy in patients with refractory or relapsed non-Hodgkin’s lymphoma (NHL).

Patients and Methods: Forty-one previously treated patients with either diffuse large cell, follicular, or peripheral T-cell NHL were treated i.v. with 100 mg/m² SAM486A as a daily 1-h infusion for 5 days repeated every 3 weeks. Treatment was continued for a total of eight cycles or until disease progression.

Results: Two patients, both with large B-cell lymphoma, showed a complete response at cycle 3 that was maintained for 13 and 28 months. Five patients had a partial response, and 3 had stable disease at last follow-up. The overall response rate (complete response plus partial response) was 18.9% for evaluable patients (7 patients). Anemia was the primary hematological toxicity and observed in 7 (17.1%) patients. Five patients experienced grade 3/4 anemia. Four patients (9.8%) experienced grade 3/4 febrile neutropenia and grade 3/4 thrombocytopenia, respectively. Nonhematological toxicities were mild to moderate in intensity. The most frequent side effects were nausea (39%), vomiting (22%), diarrhea (19.5%), asthenia (17.1%), abdominal pain (14.6%), and flushing (9.8%).

Conclusion: SAM486A has a promising clinical activity in patients with poor prognosis NHL and manageable safety profile. To further define the role of SAM486A, in the treatment of NHL, additional studies are warranted.

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