IND.216: a phase II study of buparlisib and associated biomarkers, raptor and p70S6K, in patients with relapsed and refractory chronic lymphocytic leukemia

Sarit Assouline, Lilian Amrein, Raquel Aloyz, Versha Banerji, Stephen Caplan, Carolyn Owen, Wanda Hasegawa, Sue Robinson, Sudeep Shivakumar, Anca Prica, Anthea Peters, Linda Hagerman, Laura Rodriguez, Tanya Skamene, Lawrence Panasci, Bingshu E. Chen, Annette E. Hay

Résultat de recherche: Articleexamen par les pairs

7 Citations (Scopus)

Résumé

Buparlisib is an orally available pan-Class I PI3K inhibitor, that is more potent than idelalisib in vitro. Its distinct toxicities include hyperglycemia, hypertension, and mood disturbance. IND216 is a single arm phase II trial of buparlisib in Relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Fourteen patients were enrolled, 13 were evaluable for response and toxicity. Six of 13 patients had a partial response (46%) with a median duration of response of 15.5 months, all 11 patients with tumor assessment experienced tumor shrinkage. The most common adverse events (≥15%) were hyperglycemia, fatigue, anxiety, and gastrointestinal toxicities; all were < grade 3 except for fatigue. Three patients stopped therapy for alterations in mood. Lower levels of raptor were significantly associated with greater tumor shrinkage, suggesting that raptor could be a biomarker for response. This requires further validation in a larger CLL patient cohort. The clinical activity of buparlisib is comparable to other phosphatidylinositol-3-kinase inhibitors, with a different toxicity profile.Novelty and impact Buparlisib, an oral, pan PI3 kinase inhibitor, is associated with a 46% partial response rate among patients with relapse chronic lymphocytic leukemia (CLL). This is a similar clinical activity to other phosphatidylinositol-3-kinase inhibitors tested. However, buparlisib has a distinct toxicity profile, characterized by hyperglycemia, hypertension, and mood alteration. In agreement with our previous preclinical study, our results suggest that basal raptor expression in CLL correlates with clinical response to buparlisib.

Langue d'origineEnglish
Pages (de-à)1653-1659
Nombre de pages7
JournalLeukemia and Lymphoma
Volume61
Numéro de publication7
DOI
Statut de publicationPublished - juin 6 2020
Publié à l'externeOui

Note bibliographique

Funding Information:
This research was funded by the Canadian Cancer Trials group with a grant from Novartis Canada Inc.

Publisher Copyright:
© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.

ASJC Scopus Subject Areas

  • Hematology
  • Oncology
  • Cancer Research

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