Ibrutinib plus CIT for R/R mature B-NHL in children (SPARKLE trial): initial safety, pharmacokinetics, and efficacy
Abstrakt
Pediatric patients with relapsed/refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL) have a 2-year overall survival rate with chemoimmunotherapy (CIT) of 15-33%. Rituximab plus ifosfamide, carboplatin, and etoposide (RICE) is widely used in R/R children with NHL and rituximab plus vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) has been used in Europe.
In preclinical studies, ibrutinib, a Bruton's tyrosine kinase inhibitor approved to treat adults with various B-cell malignancies in the United States and the European Union, among other countries [6], inhibited Burkitt lymphoma (BL; the predominant pediatric mature B-NHL) and diffuse large B-cell lymphoma (DLBCL) tumor cell growth, and prolonged survival in BL xenografted mice. We report safety, pharmacokinetics, and preliminary efficacy findings from the run-in stage (part 1; December 2016-December 2018) of an ongoing phase 3 trial (SPARKLE).