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

Br J Haematol. 2019 Mar;184(5):744-752. doi: 10.1111/bjh.15702. Epub 2018 Dec 5.


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.

Keywords: NHL; dasatinib; mutation analysis; phase 2 study; relapsed/refractory lymphoma.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Dasatinib / administration & dosage*
  • Disease-Free Survival
  • Female
  • Forkhead Box Protein O1 / genetics*
  • Genomics
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics*
  • Lymphoma, Non-Hodgkin* / drug therapy
  • Lymphoma, Non-Hodgkin* / genetics
  • Lymphoma, Non-Hodgkin* / mortality
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Recurrence
  • Survival Rate


  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Neoplasm Proteins
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Dasatinib