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)
Gordon, Leo I. (Northwestern University Feinberg School of Medicine)
Karmali, Reem (Northwestern University Feinberg School of Medicine)
Kaplan, Jason B. (Northwestern University Feinberg School of Medicine)
Popat, Rakesh (University College London)
Burris, Howard A. (Sarah Cannon Research Institute/Tennessee Oncology)
Ferrari, Silvia (Ospedale Papa Giovanni XXIII)
Madan, Sumit (Banner MD Anderson Cancer Center, Gilbert, AZ 85234, USA)
Patel, Manish R. (Florida Cancer Specialists/Sarah Cannon Research Institute)
Gritti, Giuseppe (Ospedale Papa Giovanni XXIII)
El-Sharkawi, Dima (Royal Marsden Hospital (Regne Unit))
Chau, F. Ian (Royal Marsden Hospital (Regne Unit))
Radford, John (University of Manchester)
de Oteyza, Jaime Pérez (Hospital Universitario HM Sanchinarro (Madrid))
Zinzani, Pier Luigi (Università di Bologna)
Iyer, Swaminathan P. (University of Texas MD Anderson Cancer Center)
Townsend, William (University College London Hospitals)
Miao, Harry (Takeda Development Center Americas)
Proscurshim, Igor (Takeda Development Center Americas)
Wang, Shining (Takeda Development Center Americas)
Katyayan, Shilpi (Labcorp Drug Development (Estats Units d'Amèrica))
Yuan, Ying (Takeda Development Center Americas)
Zhu, Jiaxi (Takeda Development Center Americas)
Stumpo, Kate (Takeda Development Center Americas)
Shou, Yaping (Takeda Development Center Americas)
Carpio Segura, Cecilia del Carmen (Vall d'Hebron Institut d'Oncologia)
Bosch José, Francesc Xavier 1947- (Universitat Autònoma de Barcelona)

Data:	2023
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Non-Hodgkin's lymphoma ; DLBCL ; Relapsed/refractory ; SYK inhibitor ; TAK-659
Publicat a:	Oncotarget, Vol. 14 (january 2023) , p. 57-70, ISSN 1949-2553

DOI: 10.18632/oncotarget.28352
PMID: 36702329

14 p, 1.3 MB

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