Efficacy and Safety of Duvelisib Following Disease Progression on Ofatumumab in Patients with Relapsed/Refractory CLL or SLL in the DUO Crossover Extension Study.

Abstract

PURPOSE:

In the phase III DUO trial, duvelisib, an oral dual PI3K-δ,γ 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.

• Authors: Matthew S Davids, Bryone J Kuss, Peter Hillmen, Marco Montillo, Carol Moreno, James Essell, Nicole Lamanna, Zsolt Nagy, Constantine S Tam, Stephan Stilgenbauer, Paolo Ghia, Julio Delgado, Stephanie Lustgarten, David T Weaver, Hagop Youssoufian, Ulrich Jäger
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 26 Issue 9 Pg. 2096-2103 (05 01 2020) ISSN: 1557-3265 [Electronic] United States
• PMID: 31964785 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: ©2020 American Association for Cancer Research.

Chemical References

• Antibodies, Monoclonal, Humanized
• Isoquinolines
• Purines
• duvelisib
• Class I Phosphatidylinositol 3-Kinases
• Class Ib Phosphatidylinositol 3-Kinase
• PIK3CD protein, human
• PIK3CG protein, human
• ofatumumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Class I Phosphatidylinositol 3-Kinases (antagonists & inhibitors)
• Class Ib Phosphatidylinositol 3-Kinase (metabolism)
• Cross-Over Studies
• Disease Progression
• Drug Resistance, Neoplasm
• Female
• Humans
• Isoquinolines (administration & dosage, adverse effects)
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, metabolism, pathology)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy, metabolism, pathology)
• Purines (administration & dosage, adverse effects)
• Salvage Therapy
• Survival Rate