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

Matthew S. Davids, Bryone 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 Weaver, Hagop Youssoufian, Ulrich Jager

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Abstract

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.

Original languageEnglish
Pages (from-to)2096-2103
Number of pages8
JournalClinical Cancer Research
Volume26
Issue number9
Early online date17 Mar 2020
DOIs
Publication statusPublished - 1 May 2020
Externally publishedYes

Keywords

  • Efficacy and Safety
  • Duvelisib
  • Disease Progression
  • Ofatumumab
  • Relapsed/Refractory
  • CLL
  • SLL

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    Davids, M. S., Kuss, B., Hillmen, P., Montillo, M., Moreno, C., Essell, J., Lamanna, N., Nagy, Z., Tam, C. S., Stilgenbauer, S., Ghia, P., Delgado, J., Lustgarten, S., Weaver, D., Youssoufian, H., & Jager, U. (2020). Efficacy and Safety of Duvelisib Following Disease Progression on Ofatumumab in Patients with Relapsed/Refractory CLL or SLL in the DUO Crossover Extension Study. Clinical Cancer Research, 26(9), 2096-2103. https://doi.org/10.1158/1078-0432.CCR-19-3061