PMID- 31621094 OWN - NLM STAT- MEDLINE DCOM- 20200511 LR - 20211204 IS - 1096-8652 (Electronic) IS - 0361-8609 (Print) IS - 0361-8609 (Linking) VI - 95 IP - 1 DP - 2020 Jan TI - Safety and activity of ibrutinib in combination with durvalumab in patients with relapsed or refractory follicular lymphoma or diffuse large B-cell lymphoma. PG - 18-27 LID - 10.1002/ajh.25659 [doi] AB - 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. CI - (c) 2019 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc. FAU - Herrera, Alex F AU - Herrera AF AUID- ORCID: 0000-0002-9665-7415 AD - Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California. FAU - Goy, Andre AU - Goy A AD - John Theurer Cancer Center Division of Lymphoma, Hackensack University Medical Center, Hackensack, New Jersey. FAU - Mehta, Amitkumar AU - Mehta A AD - Division of Hematology and Oncology, University of Alabama, Birmingham, Alabama. FAU - Ramchandren, Radhakrishnan AU - Ramchandren R AD - Department of Hematology/Oncology, Karmanos Cancer Institute, Detroit, Michigan. FAU - Pagel, John M AU - Pagel JM AD - Center for Blood Disorders and Stem Cell Transplantation, Division of Oncology, Swedish Cancer Institute, Seattle, Washington. FAU - Svoboda, Jakub AU - Svoboda J AD - Department of Medicine, Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Guan, Shanhong AU - Guan S AD - Department of Biostatistics, Pharmacyclics LLC, an AbbVie Company, Sunnyvale, California. FAU - Hill, John S AU - Hill JS AD - Department of Translational Medicine, Pharmacyclics LLC, an AbbVie Company, Sunnyvale, California. FAU - Kwei, Kevin AU - Kwei K AD - Department of Translational Medicine, Pharmacyclics LLC, an AbbVie Company, Sunnyvale, California. FAU - Liu, Emily A AU - Liu EA AD - Department of Clinical Science, Pharmacyclics LLC, an AbbVie Company, Sunnyvale, California. FAU - Phillips, Tycel AU - Phillips T AD - Rogel Cancer Center, Division of Hematology and Oncology, University of Michigan, Ann Arbor, Michigan. LA - eng GR - K12 CA001727/CA/NCI NIH HHS/United States GR - P30 CA022453/CA/NCI NIH HHS/United States GR - P50 CA107399/CA/NCI NIH HHS/United States GR - Pharmacyclics LLC, an AbbVie Company/International PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20191106 PL - United States TA - Am J Hematol JT - American journal of hematology JID - 7610369 RN - 0 (Antibodies, Monoclonal) RN - 0 (Piperidines) RN - 0 (Pyrazoles) RN - 0 (Pyrimidines) RN - 1X70OSD4VX (ibrutinib) RN - 28X28X9OKV (durvalumab) RN - JAC85A2161 (Adenine) SB - IM MH - Adenine/analogs & derivatives MH - Adult MH - Aged MH - Antibodies, Monoclonal/administration & dosage/adverse effects/therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Female MH - Humans MH - Lymphoma, Follicular/complications/*drug therapy/mortality MH - Lymphoma, Large B-Cell, Diffuse/complications/*drug therapy/mortality MH - Male MH - Middle Aged MH - Piperidines MH - Pyrazoles/administration & dosage/adverse effects/therapeutic use MH - Pyrimidines/administration & dosage/adverse effects/therapeutic use MH - Salvage Therapy/adverse effects/methods MH - Survival Analysis MH - Treatment Outcome PMC - PMC6904508 MID - NIHMS1060589 COIS- Alex F. Herrera: consultancy/advisory role for Bristol-Myers Squibb, Genentech, Merck, Pharmacyclics LLC, an AbbVie Company, Adaptive Biotechnologies, and Kite Pharma; and research funding from Bristol-Myers Squibb, Genentech, Merck, Pharmacyclics LLC, an AbbVie Company, Kite Pharma, Seattle Genetics, Immune Design, and AstraZeneca. Andre Goy: honoraria, consultancy/advisory role, research funding, and speakers bureau for Takeda, Pharmacyclics LLC, an AbbVie Company, Janssen, Acerta, Kite/Gilead, and Genentech; leadership and stock or other ownership for Cota Healthcare. Amitkumar Mehta: consultancy/advisory role for Celgene, Kite, Bristol-Myers Squibb, Carevive, Witty Health, Kyowa Kirin, and Aileron; speakers bureau for Gilead, AstraZeneca, Kite Pharma, Spectrum, Seattle Genetics, Pharmacyclics LLC, an AbbVie Company, Janssen and Kyowa Kirin; and research funding from Roche, Incyte, Bristol-Myers Squibb, Kite Pharma, Juno, Astex, ADCT, TG Therapeutics, Merck, Rhizen, Takeda, Pharmacyclics LLC, an AbbVie Company, and Seattle Genetics. Radhakrishnan Ramchandren: consultancy/advisory role from Pharmacyclics LLC, an AbbVie Company; and research funding from Janssen and Pharmacyclics LLC, an AbbVie Company. John M. Pagel: consultancy/advisory role for Pharmacyclics LLC, an AbbVie Company, and Gilead. Jakub Svoboda: honoraria from Seattle Genetics; consultancy/advisory role for Bristol-Myers Squibb, Kite, Seattle Genetics, Kyowa, Pharmacyclics LLC, an AbbVie Company, and AstraZeneca; and research funding from Bristol-Myers Squibb, Merck, Seattle Genetics, Pharmacyclics LLC, an AbbVie Company, Celgene, and Incyte. Shanhong Guan: employment with Pharmacyclics LLC, an AbbVie Company, and stock or other ownership in AbbVie. John S. Hill: employment with Amgen and Pfizer, and previously employed with Pharmacyclics LLC, an AbbVie Company; consultancy/advisory role for Adgero Biopharmaceuticals; stock or other ownership in Amgen, AbbVie, and Pfizer; and patents, royalties, or other intellectual property with Amgen and Miravant Medical. Kevin Kwei: employment with Pharmacyclics LLC, an AbbVie Company, and stock or other ownership in AbbVie and Gilead. Emily A. Liu: employment with Pharmacyclics LLC, an AbbVie Company, and stock or other ownership in AbbVie. Tycel Phillips: consultancy/advisory role for Pharmacyclics LLC, an AbbVie Company, Genentech, Seattle Genetics, Curis, Gilead, Bayer and Incyte; and research funding from Bayer, Genentech, Incyte, AbbVie, and Pharmacyclics LLC, an AbbVie Company. EDAT- 2019/10/18 06:00 MHDA- 2020/05/12 06:00 PMCR- 2019/12/17 CRDT- 2019/10/18 06:00 PHST- 2019/06/25 00:00 [received] PHST- 2019/09/12 00:00 [revised] PHST- 2019/10/11 00:00 [accepted] PHST- 2019/10/18 06:00 [pubmed] PHST- 2020/05/12 06:00 [medline] PHST- 2019/10/18 06:00 [entrez] PHST- 2019/12/17 00:00 [pmc-release] AID - AJH25659 [pii] AID - 10.1002/ajh.25659 [doi] PST - ppublish SO - Am J Hematol. 2020 Jan;95(1):18-27. doi: 10.1002/ajh.25659. Epub 2019 Nov 6.