Phase I/II study of dasatinib and exploratory genomic analysis in relapsed or refractory non-Hodgkin lymphoma

Jayadev M. Umakanthan, Javeed Iqbal, Connie L. Batlevi, Alyssa Bouska, Lynette M Smith, Valerie Shostrom, Heather Nutsch, Basem M. William, Robert G Bociek, Matthew A Lunning, Philip Jay Bierman, Anas Younes, James Olen Armitage, Julie Marie Vose

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)744-752
Number of pages9
JournalBritish Journal of Haematology
Volume184
Issue number5
DOIs
StatePublished - Mar 2019

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Keywords

  • NHL
  • dasatinib
  • mutation analysis
  • phase 2 study
  • relapsed/refractory lymphoma

ASJC Scopus subject areas

  • Hematology

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