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)

Francesc Xavier Bosch José, 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 WangShilpi Katyayan, Ying Yuan, Jiaxi Zhu, Kate Stumpo, Yaping Shou, Cecilia del Carmen Carpio Segura

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2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)57-70
Number of pages14
JournalOncotarget
Volume14
Issue number1
DOIs
Publication statusPublished - 2023

Keywords

  • Non-Hodgkin's lymphoma
  • DLBCL
  • Relapsed/refractory
  • SYK inhibitor
  • TAK-659

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