INTRODUCTION
B-cell lymphomas, DLBCL of germinal center B-cell, hypophosphatemia, neutropenia, toxicity, treatment-emergent adverse, B-cell lymphoma, lymphoid malignancy, DLBCL, lymphoma, non-Hodgkin’s lymphoma
HYPOPHOSPHATEMIA, NEUTROPENIA, DISEASE, B-CELL LYMPHOMA, SOLID TUMORS, LYMPHOMA, DIFFUSE LARGE B-CELL LYMPHOMA
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.Diffuse large B-cell lymphoma (DLBCL) is an aggressive histologic subtype of non-Hodgkin’s lymphoma and is the most common adult lymphoid malignancy in the Western world [Multi-agent salvage chemotherapy followed by autologous stem-cell transplant (ASCT) has been the standard treatment for relapsed or refractory DLBCL [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) [The safety, tolerability, and preliminary efficacy of mivavotinib were investigated in a phase I first-in-human dose escalation and expansion study conducted in patients with relapsed or refractory solid tumors or B-cell lymphomas, including DLBCL [Mivavotinib demonstrated anti-tumor activity in patients with relapsed or refractory B-cell lymphomas across different histological subtypes, including DLBCL [The current analysis provides updated results for these lymphoma patients with extended follow-up. Also included are data for an additional cohort of patients with DLBCL (