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)

Authors

Leo I Gordon
Reem Karmali
Jason B Kaplan
Rakesh Popat
Howard A Burris
Silvia Ferrari
Sumit Madan
Manish R Patel
Giuseppe Gritti
Dima El-Sharkawi
F Ian Chau
John Radford
Jaime Pérez de Oteyza
Pier Luigi Zinzani
Swaminathan P Iyer
William Townsend
Harry Miao
Igor Proscurshim
Shining Wang
Shilpi Katyayan
Ying Yuan
Jiaxi Zhu
Kate Stumpo
Yaping Shou
Cecilia Carpio
Francesc Bosch

Publication Date

1-26-2023

Journal

Oncotarget

Abstract

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.

Keywords

Humans, Vascular Endothelial Growth Factor Receptor-1, Treatment Outcome, Syk Kinase, Lymphoma, Large B-Cell, Diffuse, Protein Kinase Inhibitors, Antineoplastic Combined Chemotherapy Protocols, DLBCL, Non-Hodgkin’s lymphoma, SYK inhibitor, TAK-659, relapsed/refractory

DOI

10.18632/oncotarget.28352

PMID

36702329

PMCID

PMC9882996

PubMedCentral® Posted Date

1-26-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes