Brentuximab vedotin in the treatment of paediatric patients with relapsed or refractory Hodgkin's lymphoma: Results of a real‐life study

Abstract

Background: Brentuximab vedotin (BV) is an antibody drug-conjugated anti-CD30 approved for the treatment of adult classical Hodgkin's lymphoma (HL), whereas it is considered as off-label indication in paediatrics. The aim of the study was to evaluate the safety and efficacy of BV to treat patients aged less than 18 years with refractory/relapsed HL. Materials and methods:In this multicentre, retrospective study, 68 paediatric patients who received at least one dose of BV between November 2011 and August 2020 were enrolled. A median of nine doses of BV were administered as monotherapy (n = 31) or combined with other therapies (n = 37). BV was administrated alone as consolidation therapy after stem cell transplantation (SCT) in 12 patients, before SCT in 18 patients, whereas in 15 patients it was used before and after SCT as consolidation therapy. Median follow-up was 2.8 years (range: 0.6-8.9 years). Results:The best response was observed in the 86% of patients; the overall response rate was 66%. The 3-year progression-free survival was 58%, whereas the overall survival was 75%. No statistically significant differences between patients treated with BV monotherapy or combination were highlighted. In multivariate analysis, patients with non-nodular sclerosis HL and not transplanted had an increased risk of failure.Overall, 46% of patients had grade 3-4 adverse events that led to BV discontinuation in five of them. Conclusion:In conclusion, our study confirms that BV was a safe and effective drug, able to induce complete remission, either as monotherapy or in association with standard therapy.

Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas

“…Pulmonary toxicity seems to occur more frequently among children with r/r HL after BV administration, according to a retrospective study, but results did not reach statistical significance (for pulmonary infection: OR 4; 95% CI: 0.55 to 29.17; p = 0.08) [ 198 ]. A larger retrospective study of 68 children with r/r HL treated with BV as a single agent or combined with chemotherapy, calculated the occurrence of grade ≥3 neutropenia at 25% and all-grade infections at 22.1% (grade ≥3 at 10.3%; predominantly pneumonia followed by CMV and VZV) [ 199 ]. In general, the use of BV was associated with upper respiratory infections (very common) along with sepsis and urinary tract infections (common) [ 178 , 195 ].…”

Single or tandem autologous stem cell transplantation for treating Chinese patients with refractory/relapsed classical Hodgkin lymphoma

“…within 1 year of induction therapy, resistance to salvage therapy, and more than one salvage therapy regimen before transplantation. [14][15][16] Attempts are being made to improve the survival of high-risk patients through new drug consolidation or sequential transplantation. Our study discusses the advantages of tandem transplantation for high-risk with R/R cHL.…”

“…Approximately half of patients with chemotherapy‐sensitive disease are cured with ASCT, 8 whereas the other half, especially those with unfavorable risk factors, exhibit disease progression and have poor outcomes 9 . The following unfavorable factors are defined as high‐risk: primary induction failure, extranodal involvement, B symptoms at relapse, disease relapse within 1 year of induction therapy, resistance to salvage therapy, and more than one salvage therapy regimen before transplantation 14–16 . Attempts are being made to improve the survival of high‐risk patients through new drug consolidation or sequential transplantation.…”

“…According to data from the European Society for Blood and Marrow Transplantation, the 5‐year overall survival (OS) is only 32%. Unfavorable‐risk factors include primary induction failure, extranodal involvement, B symptoms at relapse, disease relapse within 1 year of induction therapy, resistance to salvage therapy, and more than one salvage therapy regimen in patients with R/R cHL 14–16 . However, a single transplantation is insufficient for long‐term control or to cure the disease because of unfavorable risk factors.…”

Development and Clinical Application of CAR-T Therapy

“…Brentuximab vedotin (BV), a CD30-targeting drug, is clinically indicated for treating to adults classic Hodgkin lymphoma (HL). This investigation was aiming to check whether BV is safe and efficacious in treating refractory/relapsed HL patients under 18 years of age [25].…”