Phase I/II study of dasatinib and exploratory genomic analysis in relapsed or refractory non-Hodgkin lymphoma Journal Article
| Authors: | Umakanthan, J. M.; Iqbal, J.; Batlevi, C. L.; Bouska, A.; Smith, L. M.; Shostrom, V.; Nutsch, H.; William, B. M.; Gregory Bociek, R.; Lunning, M.; Bierman, P.; Younes, A.; Armitage, J. O.; Vose, J. M. |
| Article Title: | Phase I/II study of dasatinib and exploratory genomic analysis in relapsed or refractory non-Hodgkin lymphoma |
| 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. © 2018 British Society for Haematology and John Wiley & Sons Ltd |
| Keywords: | dasatinib; mutation analysis; nhl; relapsed/refractory lymphoma; phase 2 study |
| Journal Title: | British Journal of Haematology |
| Volume: | 184 |
| Issue: | 5 |
| ISSN: | 0007-1048 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2019-03-01 |
| Start Page: | 744 |
| End Page: | 752 |
| Language: | English |
| DOI: | 10.1111/bjh.15702 |
| PROVIDER: | scopus |
| PUBMED: | 30520026 |
| PMCID: | PMC8281362 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2019 -- Source: Scopus |
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