0000000000281941
AUTHOR
Ajay K. Gopal
Identification of a genetic signature enriching for response to ibrutinib in relapsed/refractory follicular lymphoma in the DAWN phase 2 trial.
Abstract Background The single‐arm DAWN trial (NCT01779791) of ibrutinib monotherapy in patients with relapsed/refractory follicular lymphoma (FL) showed an overall response rate (ORR) of 20.9% and a median response duration of 19.4 months. This biomarker analysis of the DAWN dataset sought to determine genetic classifiers for prediction of response to ibrutinib treatment. Methods Whole exome sequencing was performed on baseline tumor samples. Potential germline variants were excluded; a custom set of 1216 cancer‐related genes was examined. Responder‐ versus nonresponder‐associated variants were identified using Fisher's exact test. Classifiers with increasing numbers of genes were created …
An open-label phase II study of ibrutinib in patients with refractory follicular lymphoma
TPS8614^ Background: Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) and comprises approximately 22% of all NHL cases. Most patients treated eventually relapse and subsequent responses and duration of responses become shorter. Patients ultimately become resistant to chemoimmunotherapy and repeated treatment-related toxicity commonly outweighs the benefit of treatment. Ibrutinib is a potent inhibitor of BTK (downstream of the B-cell receptor, BCR) that binds covalently to Cys-481 in the active site, abrogating intrinsic survival pathways (eg, ERK1/2, NF-kB, AKT) as well as survival signals from the microenvironment (eg, TNF family members: BAFF, CD40L; cytokine…
Ibrutinib As Treatment for Chemoimmunotherapy-Resistant Patients with Follicular Lymphoma: First Results from the Open-Label, Multicenter, Phase 2 DAWN Study
Abstract Background: While first line therapy for FL with chemotherapy or chemoimmunotherapy produces durable responses, most patients (pts) with FL eventually relapse. Those who become resistant to chemoimmunotherapy have limited treatment options. Ibrutinib, an inhibitor of BTK (Bruton's tyrosine kinase) and ITK (interleukin-2-inducible T-cell kinase), has demonstrated robust clinical activity in various B-cell non-Hodgkin lymphomas. Previous Phase 1 and 2 studies have shown promising results with single-agent ibrutinib in pts with relapsed or refractory FL (Bartlett NL. Blood. 2014; 800 & Fowler N. Blood. 2015; 2706). The aim of the DAWN study was to provide additional efficacy and s…
Ibrutinib as Treatment for Patients With Relapsed/Refractory Follicular Lymphoma : results From the Open-Label, Multicenter, Phase II DAWN Study
Purpose The Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated clinical activity in B-cell malignancies. The DAWN study assessed the efficacy and safety of single-agent ibrutinib in chemoimmunotherapy relapsed/refractory follicular lymphoma (FL) patients. Methods DAWN was an open-label, single-arm, phase II study of ibrutinib in patients with FL with two or more prior lines of therapy. Patients received ibrutinib 560 mg daily until progressive disease/unacceptable toxicity. The primary objective was independent review committee–assessed overall response rate (ORR; complete response plus partial response). Exploratory analyses of T-cell subsets in peripheral blood (baseline/cycle …