Spleen tyrosine kinase/FMS-like tyrosine kinase-3 inhibition in relapsed/refractory B-cell lymphoma, including diffuse large B-cell lymphoma: updated data with mivavotinib (TAK-659/CB-659).

Autor:	Gordon LI; Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA., Karmali R; Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA., Kaplan JB; Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA., Popat R; Department of Haematology, NIHR/UCLH Clinical Research Facility, University College London Hospitals NHS Foundation Trust, London, UK., Burris HA 3rd; Drug Development, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN 37203, USA., Ferrari S; Dipartimento di Oncologia ed Ematologia, Ospedale Papa Giovanni XXIII, Bergamo, Italy., Madan S; Division of Hematology and Oncology, Cancer Therapy and Research Center at University of Texas Health Science Center, San Antonio, TX 78229, USA.; Current affiliation: Division of Hematology and Oncology, Banner MD Anderson Cancer Center, Gilbert, AZ 85234, USA., Patel MR; Drug Development Unit, Florida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, FL 34232, USA., Gritti G; Dipartimento di Oncologia ed Ematologia, Ospedale Papa Giovanni XXIII, Bergamo, Italy., El-Sharkawi D; Department of Haematology, NIHR/UCLH Clinical Research Facility, University College London Hospitals NHS Foundation Trust, London, UK.; Current affiliation: Department of Haematology, Royal Marsden Hospital, Sutton, Surrey, UK., Chau FI; Department of Medicine, Royal Marsden Hospital, Sutton, Surrey, UK., Radford J; NIHR Clinical Research Facility, The Christie NHS Foundation Trust and University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., de Oteyza JP; Hematology, Hospital Universitario HM Sanchinarro, Madrid, Spain., Zinzani PL; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', Bologna, Italy.; Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy., Iyer SP; Department of Hematology and Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA.; Current affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Townsend W; Department of Haematology, NIHR/UCLH Clinical Research Facility, University College London Hospitals NHS Foundation Trust, London, UK., Miao H; Oncology Clinical Science, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA 02421, USA., Proscurshim I; Oncology Clinical Science, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA 02421, USA., Wang S; Oncology Clinical Science, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA 02421, USA., Katyayan S; Oncology Clinical Science, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA 02421, USA.; Current affiliation: Biostatistics, Labcorp Drug Development, Princeton, NJ 08540, USA., Yuan Y; Oncology Clinical Science, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA 02421, USA., Zhu J; Oncology Clinical Science, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA 02421, USA., Stumpo K; Oncology Clinical Science, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA 02421, USA., Shou Y; Oncology Clinical Science, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA 02421, USA., Carpio C; Servei d'Hematologia, Vall d'Hebron Hospital Universitari, Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain., Bosch F; Servei d'Hematologia, Vall d'Hebron Hospital Universitari, Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.; Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2023 Jan 26; Vol. 14, pp. 57-70. Date of Electronic Publication: 2023 Jan 26.
DOI:	10.18632/oncotarget.28352
Abstrakt:	We report an updated analysis from a phase I study of the spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase 3 inhibitor mivavotinib, presenting data for the overall cohort of lymphoma patients, and the subgroup of patients with diffuse large B-cell lymphoma (DLBCL; including an expanded cohort not included in the initial report). Patients with relapsed/refractory lymphoma for which no standard treatment was available received mivavotinib 60-120 mg once daily in 28-day cycles until disease progression/unacceptable toxicity. A total of 124 patients with lymphoma, including 89 with DLBCL, were enrolled. Overall response rates (ORR) in response-evaluable patients were 45% (43/95) and 38% (26/69), respectively. Median duration of response was 28.1 months overall and not reached in DLBCL responders. In subgroups with DLBCL of germinal center B-cell (GCB) and non-GCB origin, ORR was 28% (11/40) and 58% (7/12), respectively. Median progression free survival was 2.0 and 1.6 months in the lymphoma and DLBCL cohorts, respectively. Grade ≥3 treatment-emergent adverse events occurred in 96% of all lymphoma patients, many of which were limited to asymptomatic laboratory abnormalities; the most common were increased amylase (29%), neutropenia (27%), and hypophosphatemia (26%). These findings support SYK as a potential therapeutic target for the treatment of patients with B-cell lymphomas, including DLBCL. Trial registration: ClinicalTrials.gov number: NCT02000934.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu