PURPOSE: Indolent non-Hodgkin lymphoma (iNHL) remains largely incurable and often requires multiple lines of treatment after becoming refractory to standard therapies. Duvelisib was approved by the Food and Drug Administration for relapsed or refractory (RR) chronic lymphocytic leukemia or small lymphocytic lymphoma (SLL) and RR follicular lymphoma (FL) after two or more prior systemic therapies. On the basis of the activity of duvelisib, a first-in-class oral dual inhibitor of phosphoinositide 3-kinase-δ,-γ, in RR iNHL in a phase I study, the safety and efficacy of duvelisib monotherapy was evaluated in iNHL refractory to rituximab and either chemotherapy or radioimmunotherapy. PATIENTS AND METHODS: Eligible patients had measurable iNHL (FL, SLL, or marginal zone B-cell lymphoma) double refractory to rituximab (monotherapy or in combination) and to either chemotherapy or radioimmunotherapy. All were treated with duvelisib 25 mg orally twice daily in 28-day cycles until progression, unacceptable toxicity, or death. The primary end point was overall response rate (ORR) using the revised International Working Group criteria for malignant lymphoma. RESULTS: This open-label, global phase II trial enrolled 129 patients (median age, 65 years; median of three prior lines of therapy) with an ORR of 47.3% (SLL, 67.9%; FL, 42.2%; MZL, 38.9%). The estimated median duration of response was 10 months, and the estimated median progression-free survival was 9.5 months. The most frequent any-grade treatment-emergent adverse events (TEAEs) were diarrhea (48.8%), nausea (29.5%), neutropenia (28.7%), fatigue (27.9%), and cough (27.1%). Among the 88.4% of patients with at least one grade 3 or greater TEAE, the most common TEAEs were neutropenia (24.8%), diarrhea (14.7%), anemia (14.7%), and thrombocytopenia (11.6%). CONCLUSION: In the DYNAMO study, oral duvelisib monotherapy demonstrated clinically meaningful activity and a manageable safety profile in heavily pretreated, double-refractory iNHL, consistent with previous observations. Duvelisib may provide a new oral treatment option for this patient population of which many are elderly and in need of additional therapies.

Centre Hospitalier Universitaire Estaing Clermont Ferrand France

Centre intégré de santé et de services sociaux de l'Outaouais Gatineau Quebec Canada

Dana Farber Cancer Institute Boston MA

Fakultní Nemocnice Brno Brno Czech Republic

Florida Cancer Specialists Tallahassee FL

Infinity Pharmaceuticals Cambridge MA

McGill University Montreal Quebec Canada

Ospedale di Circolo e Fondazione Macchi Varese Italy

Princess Margaret Cancer Centre Toronto Ontario Canada

Ronald Reagan University of California Los Angeles Medical Center Los Angeles CA

Sarah Cannon Research Institute Nashville TN

Semmelweis Egyetem Budapest Hungary

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore MD

Tennessee Oncology Nashville TN

University College London Hospitals National Health Service Foundation Trust London United Kingdom

University of Bologna Bologna Italy

University of Liverpool Liverpool United Kingdom

Verastem Oncology Needham MA

Washington University in St Louis St Louis MO

Komentář v

J Clin Oncol. 2019 Apr 10;37(11):932-934. doi: 10.1200/JCO.19.00215. PubMed

Erratum v

J Clin Oncol. 2019 Jun 1;37(16):1448. doi: 10.1200/JCO.19.00976. PubMed

Citace poskytuje Crossref.org

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NCT01882803