Mivavotinib for Relapsed/Refractory B-cell Lymphoma (Updated)

“The current analysis provides updated results for these lymphoma patients with extended follow-up.” 

BUFFALO, NY- February 1, 2023 – A new research paper was published in Oncotarget's Volume 14 on January 26, 2023, entitled, “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).”

In this new research paper, researchers Leo I. Gordon, Reem Karmali, Jason B. Kaplan, Rakesh Popat, Howard A. Burris III, 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, and Francesc Bosch from Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, University College London Hospitals, Sarah Cannon Research Institute/Tennessee Oncology, Ospedale Papa Giovanni XXIII, University of Texas Health Science Center, Florida Cancer Specialists/Sarah Cannon Research Institute, Royal Marsden Hospital, The Christie NHS Foundation Trust and University of Manchester, Hospital Universitario HM Sanchinarro, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Università di Bologna, Houston Methodist Cancer Center, Takeda Development Center Americas, Inc. (TDCA), Vall d’Hebron Hospital Universitari, Universitat Autònoma de Barcelona, University of Texas MD Anderson Cancer Center, and Labcorp Drug Development report an updated analysis from a phase I study of the spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase 3 inhibitor mivavotinib. They present 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.

“Mivavotinib (TAK-659/CB-659) is an investigational, oral, reversible, potent dual inhibitor of spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase 3 (FLT3) [18]. SYK is an essential component of the B-cell receptor signaling pathway; abnormal SYK signaling has been implicated in the pathogenesis of DLBCL and several other B-cell malignancies [18–22].”

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.”

DOI: https://doi.org/10.18632/oncotarget.28352 

Correspondence to: Leo I. Gordon

Email: l-gordon@northwestern.edu 

Keywords: Non-Hodgkin’s lymphoma, DLBCL, relapsed/refractory, SYK inhibitor, TAK-659

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