EFFECT OF DOSE MODIFICATIONS ON RESPONSE TO DUVELISIB IN PATIENTS WITH RELAPSED/REFRACTORY CLL/SLL IN THE DUO TRIAL
Author(s): ,
Paolo Ghia
Affiliations:
Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele,Milan,Italy
,
Ian Flinn
Affiliations:
Sarah Cannon Research Institute,Nashville, TN,United States;Tennessee Oncology,Nashville, TN,United States
,
Nicole Lamanna
Affiliations:
New York Presbyterian, Columbia University Medical Center,New York, NY,United States
,
Marco Montillo
Affiliations:
Niguarda Cancer Center, Niguarda Hospital,Milan,Italy
,
Árpád Illés
Affiliations:
University of Debrecen,Debrecen,Hungary
,
Gabriel Etienne
Affiliations:
Institut Bergonie,Bordeaux,France
,
Julio Delgado
Affiliations:
Hospital Clinic,Barcelona,Spain
,
Bryone Kuss
Affiliations:
Flinders Medical Centre—Flinders University,Bedford Park, SA,Australia
,
Constantine Tam
Affiliations:
Peter MacCallum Cancer Centre, St Vincent’s Hospital and University of Melbourne,Melbourne, VIC,Australia
,
Fritz Offner
Affiliations:
University Hospital Ghent,Gent,Belgium
,
Francesc Bosch
Affiliations:
University Hospital Vall d’Hebron,Barcelona,Spain
,
Matthew Davids
Affiliations:
Dana-Farber Cancer Institute,Boston, MA,United States
,
Ulrich Jäger
Affiliations:
Medical University of Vienna,Vienna,Austria
,
Florence Cymbalista
Affiliations:
Hôpital Avicenne,Paris,France
,
David Weaver
Affiliations:
Verastem Oncology,Needham, MA,United States
,
Stephanie Lustgarten
Affiliations:
Verastem Oncology,Needham, MA,United States
,
Hagop Youssoufian
Affiliations:
Verastem Oncology,Needham, MA,United States
Stephan Stilgenbauer
Affiliations:
University Hospital Ulm,Ulm,Germany;Klinik für Innere Medizin I, Universitätsklinikum des Saarlandes,Homburg,Germany
EHA Library. Ghia P. Jun 15, 2019; 266774; PS1157
Dr. Paolo Ghia
Dr. Paolo Ghia
Contributions
Abstract

Abstract: PS1157

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
Duvelisib (DUV), a first-in-class oral dual PI3K-δ,γ inhibitor, is approved for treatment of relapsed/refractory (R/R) CLL/SLL after ≥ 2 prior therapies. In the phase 3 DUO trial, DUV 25 mg BID significantly improved efficacy vs ofatumumab (OFA; mPFS, 13.3 vs 9.9 mo; HR, 0.52 [P < .0001]; ORR, 74% vs 45% [P < .0001]) in pts with R/R CLL/SLL (Flinn et al. Blood 2018). Treatment-emergent AEs (TEAEs) of special interest (AESIs) such as infections, diarrhea, colitis, neutropenia, rash, ALT/AST elevation, and pneumonitis, were moderate and manageable with early intervention and dose modification.

Aims
To examine dose-modification patterns and their impact on response to DUV in the DUO trial. 

Methods

TEAEs were assessed according to the NCI CTCAE v4.03. Dose interruptions (DI) or reductions (DR) to 15, 10, or 5 mg BID were permitted per study protocol to manage TEAEs. Responses were assessed by an independent review committee before and after dose modifications and were analyzed using descriptive statistics.

Results
Among 158 DUV-treated pts, median duration of DUV exposure was 11.6 mo (vs 5.3 mo, OFA). DI and DR occurred in 80% (126/158) and 27% (43/158) of pts, respectively. The most common cause of DI was diarrhea (23%), followed by neutropenia (12%) and pneumonia or colitis (11% each). Among responders (n = 118), median time to first response on DUV was 1.9 mo and estimated median duration of response was 11.1 mo. Median time to first DI was 3.9 mo and median duration of DI was 15 d (range, 1-133 d). Response to DUV was improved or maintained in most pts evaluated for response who had ≥ 1 DI for > 1 wk (84% [42/50]) or > 2 wk (82% [31/38]) followed by ≥ 3 wk on DUV. In a landmark analysis, median PFS was similar in pts with DI and those without DI for > 1 wk (17.8 vs 16.3 mo) or > 2 wk (17.8 vs 16.3 mo) within the first 3 mo. The median time to DR after CR/PR was 5.6 mo (n = 25) and median duration was 3.4 mo. Median time to onset across AESIs after starting DUV ranged from 2.2 to 4.3 mo; median time to resolution was within 4 wk across AESIs. Proportions of pts experiencing AESIs were stable or decreased over time after 3-6 mo: 0-3 mo, 64% (101/158); > 3-6 mo, 63% (86/137); > 6-9 mo, 47% (54/114); > 9-12 mo, 52% (52/100), and seldom led to discontinuation of DUV (≤ 10%).

Conclusion
DI/DR can contribute to the effective management of TEAEs with DUV. These findings suggest that DI of > 1-2 weeks or more do not appear to significantly impact response to DUV or PFS.

Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Chronic lymphocytic leukemia, Clinical data, PI3K

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