TY - JOUR
T1 - Efficacy and safety of duvelisib following disease progression on ofatumumab in patients with relapsed/refractory CLL or SLL in the DUO crossover extension study
AU - Davids, Matthew S.
AU - Kuss, Bryone J.
AU - Hillmen, Peter
AU - Montillo, Marco
AU - Moreno, Carol
AU - Essell, James
AU - Lamanna, Nicole
AU - Nagy, Zsolt
AU - Tam, Constantine S.
AU - Stilgenbauer, Stephan
AU - Ghia, Paolo
AU - Delgado, Julio
AU - Lustgarten, Stephanie
AU - Weaver, David T.
AU - Youssoufian, Hagop
AU - Jäger, Ulrich
N1 - Funding Information:
M.S. Davids is a paid consultant for AbbVie, Acerta Pharma, Adaptive Biotechnologies, Ascentage Pharma, AstraZeneca, Celgene, Genentech, Gilead Sciences, Janssen, MEI Pharma, Pharmacyclics, Syros Pharmaceuticals, TG Therapeutics, Verastem Oncology, and Research to Practice, and reports receiving commercial research grants from Acerta Pharma, Ascentage Pharma, Genentech, MEI Pharma, Pharmacyclics, Surface Oncology, TG Therapeutics, and Verastem Oncology. M. Montillo reports receiving speakers bureau honoraria from AbbVie, Janssen, and Gilead, and is an unpaid consultant/advisory board member for AbbVie, AstraZeneca, Janssen, and Verastem Oncology. P. Ghia reports receiving commercial research grants from Janssen, AbbVie, Gilead, Sunesis, and Novartis, and reports receiving speakers bureau honoraria from AbbVie, Janssen, Acerta/ AstraZeneca, Dynamo, Adaptive, Verastem Oncology, BeiGene, Celgene/Juno, ArQule, and MEI. S. Lustgarten is an employee of Verastem Oncology. D.T.
Funding Information:
The authors thank the patients who participated in this study and their families. Acumen Medical Communications, LLC provided biostatistical programming support. Larra Yuelling, PhD, of Chrysalis Medical Communications, Inc provided medical writing and editorial support. This work was supported by Verastem Oncology and Infinity Pharmaceuticals Inc. Financial support was provided by Verastem Oncology.
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Purpose: In the phase III DUO trial, duvelisib, an oral dual PI3K-d,g inhibitor, demonstrated significantly improved efficacy versus ofatumumab [median (m) progression-free survival (PFS), 13.3 vs. 9.9 months (HR, 0.52; P < 0.0001); overall response rate [ORR], 74% vs. 45% (P < 0.0001)], with a manageable safety profile in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). We report results from patients with progressive disease (PD) after ofatumumab who crossed over to duvelisib in the DUO trial. Patients and Methods: Patients with radiographically confirmed PD after ofatumumab received duvelisib 25 mg twice daily in 28-day cycles until PD, intolerance, death, or study withdrawal. The primary endpoint was ORR per investigator. Secondary endpoints included duration of response (DOR), PFS, and safety. Results: As of December 14, 2018, 90 ofatumumab-treated patients in the DUO trial prior to crossover had an ORR of 29%, mDOR of 10.4 months, and mPFS of 9.4 months. After crossover, 77% of patients (69/90) achieved a response, with an mDOR of 14.9 months and mPFS of 15.7 months. Patients with del(17p) and/or TP53 mutations had similar outcomes [ORR, 77% (20/26); mPFS, 14.7 months]. Notably, 73% of patients (47/64) with disease previously refractory to ofatumumab achieved a response. The most frequent any-grade/grade 3/4 treatment-emergent adverse events were diarrhea (47%/23%), neutropenia (26%/23%), pyrexia (24%/4%), cutaneous reactions (23%/4%), and thrombocytopenia (10%/6%). Conclusions: Duvelisib demonstrated high response rates with good durability and a manageable safety profile in patients with R/R CLL/SLL who progressed on ofatumumab, including patients with high-risk disease and disease previously refractory to ofatumumab.
AB - Purpose: In the phase III DUO trial, duvelisib, an oral dual PI3K-d,g inhibitor, demonstrated significantly improved efficacy versus ofatumumab [median (m) progression-free survival (PFS), 13.3 vs. 9.9 months (HR, 0.52; P < 0.0001); overall response rate [ORR], 74% vs. 45% (P < 0.0001)], with a manageable safety profile in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). We report results from patients with progressive disease (PD) after ofatumumab who crossed over to duvelisib in the DUO trial. Patients and Methods: Patients with radiographically confirmed PD after ofatumumab received duvelisib 25 mg twice daily in 28-day cycles until PD, intolerance, death, or study withdrawal. The primary endpoint was ORR per investigator. Secondary endpoints included duration of response (DOR), PFS, and safety. Results: As of December 14, 2018, 90 ofatumumab-treated patients in the DUO trial prior to crossover had an ORR of 29%, mDOR of 10.4 months, and mPFS of 9.4 months. After crossover, 77% of patients (69/90) achieved a response, with an mDOR of 14.9 months and mPFS of 15.7 months. Patients with del(17p) and/or TP53 mutations had similar outcomes [ORR, 77% (20/26); mPFS, 14.7 months]. Notably, 73% of patients (47/64) with disease previously refractory to ofatumumab achieved a response. The most frequent any-grade/grade 3/4 treatment-emergent adverse events were diarrhea (47%/23%), neutropenia (26%/23%), pyrexia (24%/4%), cutaneous reactions (23%/4%), and thrombocytopenia (10%/6%). Conclusions: Duvelisib demonstrated high response rates with good durability and a manageable safety profile in patients with R/R CLL/SLL who progressed on ofatumumab, including patients with high-risk disease and disease previously refractory to ofatumumab.
UR - http://www.scopus.com/inward/record.url?scp=85084961014&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-19-3061
DO - 10.1158/1078-0432.CCR-19-3061
M3 - Article
C2 - 31964785
AN - SCOPUS:85084961014
SN - 1078-0432
VL - 26
SP - 2096
EP - 2103
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 9
ER -