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, R. Gregory Bociek, Matthew Lunning, Philip Bierman, Anas Younes, James O. Armitage, Julie M. Vose

Research output: Contribution to journalArticle

3 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

Keywords

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

ASJC Scopus subject areas

  • Hematology

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