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.
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.; Ferrari S.; Madan S.; Patel M.R.; Gritti G.; El-Sharkawi D.; Chau F.I.; Radford J.; 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.. - In: ONCOTARGET. - ISSN 1949-2553. - ELETTRONICO. - 14:1(2023), pp. 57-70. [10.18632/oncotarget.28352]
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
Zinzani P. L.;
2023
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.File | Dimensione | Formato | |
---|---|---|---|
oncotarget-v14-28352.pdf
accesso aperto
Tipo:
Versione (PDF) editoriale
Licenza:
Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione
1.34 MB
Formato
Adobe PDF
|
1.34 MB | Adobe PDF | Visualizza/Apri |
oncotarget-14-28352-s001.pdf
accesso aperto
Tipo:
File Supplementare
Licenza:
Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione
612.88 kB
Formato
Adobe PDF
|
612.88 kB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.