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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, L. I. Karmali, R. Kaplan, J. B. Popat, R. Burris, H. A., 3rd Ferrari, S. Madan, S. Patel, M. R. Gritti, G. El-Sharkawi, D.
Gordon, L. I.
Karmali, R.
Kaplan, J. B.
Popat, R.
Burris, H. A., 3rd
Ferrari, S.
Madan, S.
Patel, M. R.
Gritti, G.
El-Sharkawi, D.
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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.
Authors
Gordon, L. I.
Karmali, R.
Kaplan, J. B.
Popat, R.
Burris, H. A., 3rd
Ferrari, S.
Madan, S.
Patel, M. R.
Gritti, G.
El-Sharkawi, D.
Chau, F. I.
Radford, John A
de Oteyza, J. P.
Zinzani, P. L.
Iyer, S. P.
Townsend, W.
Miao, H.
Proscurshim, I.
Wang, S.
Katyayan, S.
Yuan, Y.
Zhu, J.
Stumpo, K.
Shou, Y.
Carpio, C.
Bosch, F.
Karmali, R.
Kaplan, J. B.
Popat, R.
Burris, H. A., 3rd
Ferrari, S.
Madan, S.
Patel, M. R.
Gritti, G.
El-Sharkawi, D.
Chau, F. I.
Radford, John A
de Oteyza, J. P.
Zinzani, P. L.
Iyer, S. P.
Townsend, W.
Miao, H.
Proscurshim, I.
Wang, S.
Katyayan, S.
Yuan, Y.
Zhu, J.
Stumpo, K.
Shou, Y.
Carpio, C.
Bosch, F.
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Date
2023
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Article
Citation
Gordon LI, Karmali R, Kaplan JB, Popat R, Burris HA, 3rd, Ferrari S, et al. 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). Oncotarget. 2023 Jan 26;14:57-70. PubMed PMID: 36702329. Pubmed Central PMCID: PMC9882996. Epub 2023/01/27. eng.