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PI3Kδ Inhibition by Idelalisib in patients with relapsed indolent lymphoma

PI3Kδ Inhibition by Idelalisib in patients with relapsed indolent lymphoma
PI3Kδ Inhibition by Idelalisib in patients with relapsed indolent lymphoma
BACKGROUND
Phosphatidylinositol-3-kinase delta (PI3Kδ) mediates B-cell receptor signaling and microenvironmental support signals that promote the growth and survival of malignant B lymphocytes. In a phase 1 study, idelalisib, an orally active selective PI3Kδ inhibitor, showed antitumor activity in patients with previously treated indolent non-Hodgkin's lymphomas.

METHODS
In this single-group, open-label, phase 2 study, 125 patients with indolent non-Hodgkin's lymphomas who had not had a response to rituximab and an alkylating agent or had had a relapse within 6 months after receipt of those therapies were administered idelalisib, 150 mg twice daily, until the disease progressed or the patient withdrew from the study. The primary end point was the overall rate of response; secondary end points included the duration of response, progression-free survival, and safety.

RESULTS
The median age of the patients was 64 years (range, 33 to 87); patients had received a median of four prior therapies (range, 2 to 12). Subtypes of indolent non-Hodgkin's lymphoma included follicular lymphoma (72 patients), small lymphocytic lymphoma (28), marginal-zone lymphoma (15), and lymphoplasmacytic lymphoma with or without Waldenström's macroglobulinemia (10). The response rate was 57% (71 of 125 patients), with 6% meeting the criteria for a complete response. The median time to a response was 1.9 months, the median duration of response was 12.5 months, and the median progression-free survival was 11 months. Similar response rates were observed across all subtypes of indolent non-Hodgkin's lymphoma, though the numbers were small for some categories. The most common adverse events of grade 3 or higher were neutropenia (in 27% of the patients), elevations in aminotransferase levels (in 13%), diarrhea (in 13%), and pneumonia (in 7%).

CONCLUSIONS
In this single-group study, idelalisib showed antitumor activity with an acceptable safety profile in patients with indolent non-Hodgkin's lymphoma who had received extensive prior treatment. (Funded by Gilead Sciences and others; ClinicalTrials.gov number, NCT01282424. opens in new tab.)
0028-4793
1008-1018
Gopal, Ajay K.
376ed2c6-0d61-4668-8b55-48997a6f206b
Kahl, Brad S.
c705566a-f531-41e8-9ef7-0fcf00a207aa
De Vos, Sven
312eac0f-fed3-41fa-b830-1eaf42844fb2
Wagner-johnston, Nina D.
774b3892-c006-4bcc-8c6a-42636ffdcc53
Schuster, Stephen J.
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Jurczak, Wojciech J.
847246a9-703f-4150-a718-e1b513cb9c27
Flinn, Ian W.
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Flowers, Christopher R.
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Martin, Peter
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Viardot, Andreas
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Blum, Kristie A.
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Goy, Andre H.
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Davies, Andrew J.
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Zinzani, Pier Luigi
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Dreyling, Martin
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Johnson, Dave
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Miller, Langdon L.
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Holes, Leanne
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Li, Daniel
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Dansey, Roger D.
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Godfrey, Wayne R.
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Salles, Gilles A.
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Gopal, Ajay K.
376ed2c6-0d61-4668-8b55-48997a6f206b
Kahl, Brad S.
c705566a-f531-41e8-9ef7-0fcf00a207aa
De Vos, Sven
312eac0f-fed3-41fa-b830-1eaf42844fb2
Wagner-johnston, Nina D.
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Schuster, Stephen J.
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Jurczak, Wojciech J.
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Flinn, Ian W.
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Flowers, Christopher R.
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Martin, Peter
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Viardot, Andreas
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Blum, Kristie A.
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Goy, Andre H.
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Davies, Andrew J.
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Zinzani, Pier Luigi
c8a817bb-0f54-4bde-90b2-d3339ed8fff5
Dreyling, Martin
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Johnson, Dave
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Miller, Langdon L.
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Holes, Leanne
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Li, Daniel
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Dansey, Roger D.
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Godfrey, Wayne R.
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Salles, Gilles A.
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Gopal, Ajay K., Kahl, Brad S., De Vos, Sven, Wagner-johnston, Nina D., Schuster, Stephen J., Jurczak, Wojciech J., Flinn, Ian W., Flowers, Christopher R., Martin, Peter, Viardot, Andreas, Blum, Kristie A., Goy, Andre H., Davies, Andrew J., Zinzani, Pier Luigi, Dreyling, Martin, Johnson, Dave, Miller, Langdon L., Holes, Leanne, Li, Daniel, Dansey, Roger D., Godfrey, Wayne R. and Salles, Gilles A. (2014) PI3Kδ Inhibition by Idelalisib in patients with relapsed indolent lymphoma. New England Journal of Medicine, 370 (11), 1008-1018. (doi:10.1056/NEJMoa1314583).

Record type: Article

Abstract

BACKGROUND
Phosphatidylinositol-3-kinase delta (PI3Kδ) mediates B-cell receptor signaling and microenvironmental support signals that promote the growth and survival of malignant B lymphocytes. In a phase 1 study, idelalisib, an orally active selective PI3Kδ inhibitor, showed antitumor activity in patients with previously treated indolent non-Hodgkin's lymphomas.

METHODS
In this single-group, open-label, phase 2 study, 125 patients with indolent non-Hodgkin's lymphomas who had not had a response to rituximab and an alkylating agent or had had a relapse within 6 months after receipt of those therapies were administered idelalisib, 150 mg twice daily, until the disease progressed or the patient withdrew from the study. The primary end point was the overall rate of response; secondary end points included the duration of response, progression-free survival, and safety.

RESULTS
The median age of the patients was 64 years (range, 33 to 87); patients had received a median of four prior therapies (range, 2 to 12). Subtypes of indolent non-Hodgkin's lymphoma included follicular lymphoma (72 patients), small lymphocytic lymphoma (28), marginal-zone lymphoma (15), and lymphoplasmacytic lymphoma with or without Waldenström's macroglobulinemia (10). The response rate was 57% (71 of 125 patients), with 6% meeting the criteria for a complete response. The median time to a response was 1.9 months, the median duration of response was 12.5 months, and the median progression-free survival was 11 months. Similar response rates were observed across all subtypes of indolent non-Hodgkin's lymphoma, though the numbers were small for some categories. The most common adverse events of grade 3 or higher were neutropenia (in 27% of the patients), elevations in aminotransferase levels (in 13%), diarrhea (in 13%), and pneumonia (in 7%).

CONCLUSIONS
In this single-group study, idelalisib showed antitumor activity with an acceptable safety profile in patients with indolent non-Hodgkin's lymphoma who had received extensive prior treatment. (Funded by Gilead Sciences and others; ClinicalTrials.gov number, NCT01282424. opens in new tab.)

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More information

e-pub ahead of print date: 22 January 2014
Published date: 13 March 2014

Identifiers

Local EPrints ID: 436256
URI: http://eprints.soton.ac.uk/id/eprint/436256
ISSN: 0028-4793
PURE UUID: e9971fa3-086b-4373-8350-ca0183125ce2
ORCID for Andrew J. Davies: ORCID iD orcid.org/0000-0002-7517-6938

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Date deposited: 05 Dec 2019 17:30
Last modified: 17 Mar 2024 03:14

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Contributors

Author: Ajay K. Gopal
Author: Brad S. Kahl
Author: Sven De Vos
Author: Nina D. Wagner-johnston
Author: Stephen J. Schuster
Author: Wojciech J. Jurczak
Author: Ian W. Flinn
Author: Christopher R. Flowers
Author: Peter Martin
Author: Andreas Viardot
Author: Kristie A. Blum
Author: Andre H. Goy
Author: Pier Luigi Zinzani
Author: Martin Dreyling
Author: Dave Johnson
Author: Langdon L. Miller
Author: Leanne Holes
Author: Daniel Li
Author: Roger D. Dansey
Author: Wayne R. Godfrey
Author: Gilles A. Salles

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