The addition of ibrutinib to multiagent chemotherapy failed to improve event-free survival (EFS) or overall survival (OS) among pediatric patients with relapsed/refractory, mature B-cell non-Hodgkin lymphomas (B-NHL), according to the final results of the phase 3 SPARKLE trial published in Blood Advances.
“Our data show that a large international study from a very rare population of patients with relapsed/refractory B-NHL is possible, leading to better therapies for children and young adults with mature B-NHL,” the authors wrote in their report.
In the open-label, phase 3 SPARKLE trial (ClinicalTrials.gov Identifier: NCT02703272), 51 patients with relapsed/refractory B-NHL and who were diagnosed at age younger than 18 were randomly assigned 2:1 to receive ibrutinib plus modified rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI). The primary endpoint was EFS.
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The median age at baseline was 15 years. The most common B-NHLs were diffuse large B-cell lymphoma, Burkitt lymphoma, and primary mediastinal B-cell lymphoma.
There was no significant difference in EFS at the planned interim analysis, with a median of 6.1 months in the ibrutinib group and 7.0 months with RICE or RVICI alone (hazard ratio [HR], 0.9; 95% CI, 0.5-1.6; P =.387). The 2-year EFS was 14% with ibrutinib and 13% with RICE or RVICI alone.
The OS was also similar, with a median of 14.1 and 11.1 months in the ibrutinib and RICE or RVICI alone groups, respectively (HR, 0.9; 90% CI, 0.5-1.7; P =.789). At 3 years, the OS rates were 36% with ibrutinib and 30% with RICE or RVICI alone.
The overall response rate was lower with ibrutinib at 69% compared with 81% with RICE or RVICI alone. The median time to response was 0.89 and 0.82 months, respectively, and the median duration of response was 6.0 and 65.months, respectively.
Grade 3 or higher treatment-emergent adverse events occurred among all patients. The most common grade 3 or higher TEAEs in the ibrutinib arm was thrombocytopenia with platelet count decrease, neutropenia with neutrophil count decrease, anemia, febrile neutropenia, and vomiting. Discontinuation of ibrutinib occurred among 3% of patients.
The authors concluded that “there was no benefit of ibrutinib added to RICE/RVICI in pediatric patients with relapsed/refractory mature B-NHL.”
Disclosures: This study was supported by Janssen Research and Development. Please see the original reference for a full list of disclosures.
Reference
Burke GAA, Vinti L, Kabickova E, et al. Ibrutinib plus RICE or RVICI for relapsed/refractory mature B-cell non-Hodgkin lymphoma in children and young adults: SPARKLE trial. Blood Adv. 2023;7:602-610. doi: 10.1182/bloodadvances.2022008802
