Phase II study of idelalisib, a selective inhibitor of PI3Kδ, for relapsed/refractory classical Hodgkin lymphoma Journal Article

   

Authors:	Gopal, A. K.; Fanale, M. A.; Moskowitz, C. H.; Shustov, A. R.; Mitra, S.; Ye, W.; Younes, A.; Moskowitz, A. J.
Article Title:	Phase II study of idelalisib, a selective inhibitor of PI3Kδ, for relapsed/refractory classical Hodgkin lymphoma
Abstract:	Background: The phosphatidylinositol-3-kinase delta (PI3K delta) inhibitor idelalisib has been shown to block downstream intracellular signaling, reduce the production of prosurvival chemokines and induce apoptosis in classical Hodgkin lymphoma (HL) cell lines. It has also been shown to inhibit regulatory T cells and myeloid-derived suppressor cells in other tumor models. We hypothesized that inhibiting PI3K delta would have both direct and indirect antitumor effects by directly targeting the malignant cells as well as modulating the inflammatory microenvironment. We tested this hypothesis in a phase II study. Patients and methods: We enrolled 25 patients with relapsed/ refractory HL with a median age of 42 years and who had previously received a median of five therapies including 18 (72%) with failed autologous stem cell transplant, 23 (92%) with failed brentuximab vedotin, and 11 (44%) with prior radiation therapy. Idelalisib was administered at 150 mg two times daily; an increase to 300mg two times daily was permitted at the time of disease progression. Results: The overall response rate to idelalisib therapy was 20% (95% confidence interval: 6.8%, 40.7%) with a median time to response of 2.0 months. Seventeen patients (68%) experienced reduction in target lesions with one complete remission and four partial remissions. The median duration of response was 8.4 months and median progression-free survival was 2.3 months. The most common grade >= 3 adverse event was elevation of alanine aminotransferase (two patients, 8%). Diarrhea/colitis was seen in three patients and was grade 1-2. There was one adverse event leading to death (hypoxia). Conclusions: Idelalisib was tolerable and had modest single-agent activity in heavily pretreated patients with HL. Rational combinations with other novel agents may improve response rate and duration of response.
Keywords:	immunotherapy; microenvironment; guidelines; hodgkin lymphoma; regulatory t-cells; transplant; brentuximab vedotin; cal-101; p110-delta; pi3k delta; idelalisib therapy
Journal Title:	Annals of Oncology
Volume:	28
Issue:	5
ISSN:	0923-7534
Publisher:	Oxford University Press
Date Published:	2017-05-01
Start Page:	1057
End Page:	1063
Language:	English
ACCESSION:	WOS:000400283600023
DOI:	10.1093/annonc/mdx028
PROVIDER:	wos
PUBMED:	28327905
PMCID:	PMC6246229
Notes:	Article -- Source: Wos

https://synapse.mskcc.org/synapse/works/has_related_data_chk/110599