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Biodistribution, shedding, and transmissibility of the oncolytic virus talimogene laherparepvec in patients with melanoma.
Andtbacka, Robert H I; Amatruda, Thomas; Nemunaitis, John; Zager, Jonathan S; Walker, John; Chesney, Jason A; Liu, Kate; Hsu, Cheng-Pang; Pickett, Cheryl A; Mehnert, Janice M.
Afiliação
  • Andtbacka RHI; University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.
  • Amatruda T; Minnesota Oncology and Virginia Piper Cancer Institute, Fridley, MN, USA. Electronic address: thomas.amatruda@usoncology.com.
  • Nemunaitis J; College of Medicine and Life Sciences, The University of Toledo, Toledo, OH, USA.
  • Zager JS; Moffitt Cancer Center, 10920 N. McKinley Drive, Tampa, FL 33612, USA.
  • Walker J; University of Alberta, Edmonton, AB, Canada.
  • Chesney JA; James Graham Brown Cancer Center, University of Louisville, 529 South Jackson Street, Louisville, KY 40205, USA.
  • Liu K; Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, USA.
  • Hsu CP; Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, USA.
  • Pickett CA; Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, USA. Electronic address: cpickett@amgen.com.
  • Mehnert JM; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
EBioMedicine ; 47: 89-97, 2019 Sep.
Article em En | MEDLINE | ID: mdl-31409575
BACKGROUND: Talimogene laherparepvec (T-VEC) is an intralesionally delivered, modified herpes simplex virus type-1 oncolytic immunotherapy. The biodistribution, shedding, and potential transmission of T-VEC was systematically evaluated during and after completion of therapy in adults with advanced melanoma. METHODS: In this phase 2, single-arm, open-label study, T-VEC was administered into injectable lesions initially at 106 plaque-forming units (PFU)/mL, 108 PFU/mL 21 days later, and 108 PFU/mL every 14 (±3) days thereafter. Injected lesions were covered with occlusive dressings for ≥1 week. Blood, urine, and swabs from exterior of occlusive dressings, surface of injected lesions, oral mucosa, anogenital area, and suspected herpetic lesions were collected throughout the study. Detectable T-VEC DNA was determined for each sample type; infectivity was determined for all swabs with detectable T-VEC DNA. FINDINGS: Sixty patients received ≥1 dose of T-VEC. During cycles 1-4, T-VEC DNA was detected in blood (98·3% of patients, 36·7% of samples), urine (31·7% of patients, 3·0% of samples) and swabs from injected lesions (100% of patients, 57·6% of samples), exterior of dressings (80% of patients,19·5% of samples), oral mucosa (8·3% of patients, 2·5% of samples), and anogenital area (8·0% of patients, 1·1% of samples). During the safety follow-up period, T-VEC DNA was only detected on swabs from injected lesions (14% of patients, 5.8% of samples). T-VEC DNA was detected in 4/37 swabs (3/19 patients) of suspected herpetic lesions. Among all samples, only those from the surface of injected lesions tested positive for infectivity (8/740 [1·1%]). Three close contacts reported signs and symptoms of suspected herpetic origin; however, no lesions had detectable T-VEC DNA. INTERPRETATION: Using current guidelines, T-VEC can be administered safely to patients with advanced melanoma and is unlikely to be transmitted to close contacts with appropriate use of occlusive dressings. FUND: This study was funded by Amgen Inc.: ClinicalTrials.gov, NCT02014441.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Produtos Biológicos / Vírus Oncolíticos / Terapia Viral Oncolítica / Melanoma Tipo de estudo: Clinical_trials / Diagnostic_studies / Etiology_studies / Guideline Limite: Adult / Aged / Aged80 / Humans / Middle aged Idioma: En Revista: EBioMedicine Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Produtos Biológicos / Vírus Oncolíticos / Terapia Viral Oncolítica / Melanoma Tipo de estudo: Clinical_trials / Diagnostic_studies / Etiology_studies / Guideline Limite: Adult / Aged / Aged80 / Humans / Middle aged Idioma: En Revista: EBioMedicine Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos