An interim analysis of the phase 3 SPARKLE trial showed that ibrutinib had efficacy similar to that of rituximab plus ifosfamide, carboplatin, etoposide, and dexamethasone (RICE) and rituximab plus vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) with no new safety concerns in pediatric patients with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL). Results from this analysis were presented at the 2021 American Society of Pediatric Hematology/Oncology (ASPHO) meeting.
“Children with relapsed and refractory mature B-NHL have had very low rates of survival,” said G. A. Amos Burke, MD, in a prerecorded presentation of the analysis. The 2-year overall survival (OS) for this patient population is 30% or less with chemoimmunotherapy.
The phase 3, open-label SPARKLE trial (ClinicalTrials.gov Identifier: NCT02703272) compared ibrutinib plus standard RICE/RVICI with RICE/RVICI alone. The primary endpoint was median event-free survival (EFS), while also assessing safety. OS was a secondary endpoint.
A total of 51 patients were randomly assigned to either the ibrutinib arm (35 patients) or to the RICE/RVICI arm (16 patients). The median age was 15.0 years for patients in the ibrutinib arm and 14.5 years for patients in the RICE/RVICI arm. The median EFS was 5.36 months vs 6.97 months, respectively, and median OS was 13.44 months vs 11.07 months, respectively. These results were not statistically significant.
In terms of safety, the overall treatment-emergent adverse event (TEAE) profiles were similar between both arms. The 2 arms had comparable rates of grade 3 or higher TEAEs (both 100%), serious TEAEs (71.4% with ibrutinib vs 73.3% with RICE/RVICI), and TEAEs leading to death (11.4% with ibrutinib vs 13.3% with RICE/RVICI).
Among patients receiving ibrutinib, 51.4% experienced serious ibrutinib-related TEAEs. A total of 2.9% had TEAEs that led to discontinuation of ibrutinib. Occurrences of major hemorrhage were higher with ibrutinib plus RICE/RVICI compared with RICE/RVICI alone (17.1% vs 6.7%), and occurrences of infections were lower (51.4% vs 66.7%, respectively). Death occurred in 18 patients (51.4%) receiving ibrutinib and in 10 patients (66.7%) receiving chemoimmunotherapy.
Ultimately, the analysis found that EFS met the futility criteria (1-sided P ≥.341), therefore enrollment ended. No new or unexpected safety signals were seen, but there was a higher incidence of major hemorrhage seen with ibrutinib.
Disclosures: This research was supported by Janssen Research & Development, LLC. Please see the original reference for a full list of authors’ disclosures.
Burke GAA, Locatelli F, Kabickova E, et al. Ibrutinib+RICE/RVICI for R/R mature B-NHL in children/young adults: SPARKLE trial interim analysis. Poster presented at: 2021 American Society of Pediatric Hematology/Oncology meeting; April 21-23, 2021; virtual.