Safety and activity of ibrutinib in combination with durvalumab in patients with relapsed or refractory follicular lymphoma or diffuse large B‐cell lymphoma

This phase 1b/2, multicenter, open‐label study evaluated ibrutinib plus durvalumab in relapsed/refractory follicular lymphoma (FL) or diffuse large B‐cell lymphoma (DLBCL). Patients were treated with once‐daily ibrutinib 560 mg plus durvalumab 10 mg/kg every 2 weeks in 28‐day cycles in phase 1b with...

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Bibliographic Details
Published in:American journal of hematology 2020-01, Vol.95 (1), p.18-27
Main Authors: Herrera, Alex F., Goy, Andre, Mehta, Amitkumar, Ramchandren, Radhakrishnan, Pagel, John M., Svoboda, Jakub, Guan, Shanhong, Hill, John S., Kwei, Kevin, Liu, Emily A., Phillips, Tycel
Format: Article
Language:English
Subjects:
Adult
Aged
Antibodies, Monoclonal - administration & dosage
Antibodies, Monoclonal - adverse effects
Antibodies, Monoclonal - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Appetite loss
B-cell lymphoma
Diarrhea
Dosage
Edema
Female
Hematology
Humans
Immunotherapy
Lymphoma
Lymphoma, Follicular - complications
Lymphoma, Follicular - drug therapy
Lymphoma, Follicular - mortality
Lymphoma, Large B-Cell, Diffuse - complications
Lymphoma, Large B-Cell, Diffuse - drug therapy
Lymphoma, Large B-Cell, Diffuse - mortality
Male
Middle Aged
Monoclonal antibodies
Nausea
Neutropenia
PD-L1 protein
Pyrazoles - administration & dosage
Pyrazoles - adverse effects
Pyrazoles - therapeutic use
Pyrimidines - administration & dosage
Pyrimidines - adverse effects
Pyrimidines - therapeutic use
Salvage Therapy - adverse effects
Salvage Therapy - methods
Survival Analysis
Targeted cancer therapy
Toxicity
Treatment Outcome
Vomiting
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Summary:This phase 1b/2, multicenter, open‐label study evaluated ibrutinib plus durvalumab in relapsed/refractory follicular lymphoma (FL) or diffuse large B‐cell lymphoma (DLBCL). Patients were treated with once‐daily ibrutinib 560 mg plus durvalumab 10 mg/kg every 2 weeks in 28‐day cycles in phase 1b without dose‐limiting toxicities, confirming the phase 2 dosing. Sixty‐one patients with FL (n = 27), germinal center B‐cell (GCB) DLBCL (n = 16), non‐GCB DLBCL (n = 16), and unspecified DLBCL (n = 2) were treated. Overall response rate (ORR) was 25% in all patients, 26% in patients with FL, 13% in patients with GCB DLBCL, and 38% in patients with non‐GCB DLBCL. Overall, median progression‐free survival was 4.6 months and median overall survival was 18.1 months; both were longer in patients with FL than in patients with DLBCL. The most frequent treatment‐emergent adverse events (AEs) in patients with FL and DLBCL, respectively, were diarrhea (16 [59%]; 16 [47%]), fatigue (12 [44%]; 16 [47%]), nausea (9 [33%]; 12 [35%]), peripheral edema (7 [26%]; 13 [38%]), decreased appetite (8 [30%]; 11 [32%]), neutropenia (6 [22%]; 11 [32%]), and vomiting (5 [19%]; 12 [35%]). Investigator‐defined immune‐related AEs were reported in 12/61 (20%) patients. Correlative analyses were conducted but did not identify any conclusive biomarkers of response. In FL, GCB DLBCL, and non‐GCB DLBCL, ibrutinib plus durvalumab demonstrated similar activity to single‐agent ibrutinib with the added toxicity of the PD‐L1 blockade; the combination resulted in a safety profile generally consistent with those known for each individual agent.
ISSN:0361-8609
1096-8652
DOI:10.1002/ajh.25659