Initial testing of lenalidomide by the pediatric preclinical testing program

C. Patrick Reynolds, Min H. Kang, Stephen T. Keir, Richard Gorlick, E. Anders Kolb, Richard Lock, John M. Maris, Hernan Carol, Christopher L. Morton, Catherine A. Billups, Malcolm A. Smith, Peter J. Houghton

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: Lenalidomide, a novel immunomodulatory agent, is reported to modulate stem cell differentiation, and have direct antiproliferative activity as well as inhibit inflammation and hyperalgesia. On the basis of this varied pharmacological profile, lenalidomide is under investigation as a treatment for a range of oncologic indications. Procedures: Lenalidomide was evaluated against the PPTP in vitro panel using 96-hr exposure at concentrations ranging from 1nM to 10μM. It was tested against the PPTP in vivo panels at a dose of 30mg/kg administered orally (PO) once daily for a planned for 6 weeks. Results: In vitro activity was not observed at concentrations up to 10μM. Lenalidomide was well tolerated, and induced significant differences in EFS distribution compared to control in 7 of 37 (18.9%) of the evaluable solid tumor xenografts and in 0 of 8 (0%) of the evaluable ALL xenografts. The best response in the solid tumor panel was PD2 [progressive disease with growth delay (EFS T/C>1.5)], observed in 4 of 37 (10.8%) solid tumor xenografts. A single ALL xenograft showed a PD2 response. Conclusions: Direct antiproliferative effects of lenalidomide were not observed in vitro. In vivo lenalidomide demonstrated low activity against tumors in immune-deficient mice. Our results suggest that lenalidomide's utility in the pediatric clinical setting may depend upon its ability to induce antitumor activity through effects on host immune and stromal cells rather than through direct effects on tumor cells.

Original languageEnglish (US)
Pages (from-to)606-611
Number of pages6
JournalPediatric Blood and Cancer
Volume57
Issue number4
DOIs
StatePublished - Oct 1 2011

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Keywords

  • Developmental therapeutics
  • Lenalidomide
  • Preclinical testing

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Reynolds, C. P., Kang, M. H., Keir, S. T., Gorlick, R., Kolb, E. A., Lock, R., Maris, J. M., Carol, H., Morton, C. L., Billups, C. A., Smith, M. A., & Houghton, P. J. (2011). Initial testing of lenalidomide by the pediatric preclinical testing program. Pediatric Blood and Cancer, 57(4), 606-611. https://doi.org/10.1002/pbc.22877