Phase I/II study of dasatinib and exploratory genomic analysis in relapsed or refractory non-Hodgkin lymphoma.
Br J Haematol
; 184(5): 744-752, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30520026
ABSTRACT
Relapsed or refractory non-Hodgkin lymphomas (NHLs) often carry poor prognosis and pose management challenges. We evaluated the safety and efficacy of dasatinib, a broad-spectrum multi-kinase inhibitor in relapsed/refractory NHL with correlative genomic analysis in a Phase I/II trial. The study included 33 patients with various sub-types of NHL who had received at least one prior therapy. The most common sub-types were diffuse large B-cell lymphoma (24%), follicular lymphoma, grade 1/2 (21%) and peripheral T-cell lymphoma not otherwise specified (PTCL-NOS; 21%). Most patients were heavily pre-treated, including 42% with more than four prior therapies, 67% with rituximab exposure and 24% with prior autologous transplant. In this cohort, dasatinib showed modest activity in evaluable patients with an objective response rate of 29% (7/24) and clinical benefit rate of 71% (17/24). In 32 patients with outcome data, median progression-free survival was 3 months and median overall survival was 22·4 months. There were two patients with sustained complete responses, both with PTCL-NOS histology. The side effect profile was consistent with prior studies, with pleural effusion being the most common non-haematological toxicity. Exploratory genomic analysis showed two cases of PTCL-NOS with sustained response had a common mutation in LRRK2 and high prevalence of FOXO1 mutation in relapsed/refractory follicular lymphoma.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfoma não Hodgkin
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Dasatinibe
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Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina
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Proteína Forkhead Box O1
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Proteínas de Neoplasias
Tipo de estudo:
Clinical_trials
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Br J Haematol
Ano de publicação:
2019
Tipo de documento:
Article