Brentuximab vedotin for paediatric relapsed or refractory Hodgkin's lymphoma and anaplastic large-cell lymphoma: a multicentre, open-label, phase 1/2 study

Locatelli, Franco; Mauz-Koerholz, Christine; Neville, Kathleen; Llort, Anna; Beishuizen, Auke; Daw, Stephen; Pillon, Marta; Aladjidi, Nathalie; Klingebiel, Thomas; Landman‐Parker, Judith; Medina-Sansón, Aurora; August, Keith J.; Sachs, Jessica; Hoffman, K. R.; Kinley, Judith; Song, Sam; Song, Gregory; Zhang, Stephen X.; Suri, Ajit; Gore, Lia

doi:10.1016/s2352-3026(18)30153-4

Cited by 83 publications

(108 citation statements)

References 22 publications

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“…The overall response rate in early phase trials of Bv as a single agent in paediatric HL was 47% (95% CI 21–73), notably lower than the response in adult early phase trials (Locatelli et al , ). All patients had a treatment‐emergent adverse event and 44% had at least one ≥grade 3 adverse event; 33% patients had transient, peripheral neuropathy.…”

Section: Primary Prevention To Close the Survivorship Gapmentioning

confidence: 88%

Closing the survivorship gap in children and adolescents with Hodgkin lymphoma

2019

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Summary The treatment of Hodgkin lymphoma (HL) is one of early success. However, disease‐free survival (DFS) does not reflect latent organ injury and its impact on health status and well‐being beyond 5 years. In fact, we are at a crossroads, in terms of needing individualized approaches to maintain DFS, while minimizing late effects and preserving health‐related quality of life (HRQoL). Premature morbidity and mortality translate to a high societal cost associated with the potential number of productive life years ahead in this population who are young at diagnosis. The discordance between short‐term lymphoma‐free survival and long‐term health and HRQoL creates a “survivorship gap” which can be characterized for individuals and for subgroups of patients. The current review delineates contributors to compromised outcomes and health status in child and adolescent (paediatric) HL and frames the survivorship gap in terms of primary and secondary prevention. Primary prevention aims to titrate therapy. Secondary prevention entails strategies to intervene against late effects. Bridging the survivorship gap will be attained with enhanced knowledge of and attention to biology of the tumour and microenvironment, host genetic factors, HRQoL and sub‐populations with disparate outcomes.

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Section: Primary Prevention To Close the Survivorship Gapmentioning

confidence: 88%

Closing the survivorship gap in children and adolescents with Hodgkin lymphoma

2019

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“…A number of adult HL and NHL trials have since published their results, including some incorporating adolescent and young adult patients (Sekimizu et al , ), but it wasn't until 2012 that a paediatric‐specific phase I/II trial for relapsed or refractory ALCL patients began (NCT01492088). Early results from this study have recently been reported, and are disappointing: only 53% of ALCL patients achieved an overall response, and all patients on the study experienced adverse events, with 44% suffering at least one grade 3 or worse treatment‐related side‐effect (Locatelli et al , ). In addition, questions remain as to how to treat patients failing BV, as this has been shown to be associated with a very poor outcome (Chihara et al , ).…”

Section: Current Avenues For Treatment; Breaking the Ceiling?mentioning

confidence: 92%

From bench to bedside: the past, present and future of therapy for systemic paediatric ALCL, ALK+

et al. 2019

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Anaplastic large cell lymphoma (ALCL) is a T cell Non-Hodgkin Lymphoma that mainly presents in paediatric and young adult patients. The majority of cases express a chimeric fusion protein resulting in hyperactivation of anaplastic lymphoma kinase (ALK) as the consequence of a chromosomal translocation. Rarer cases lack expression of ALK fusion proteins and are categorised as ALCL, ALKÀ. An adapted regimen of an historic chemotherapy backbone is still used to this day, yielding overall survival (OS) of over 90% but with event-free survival (EFS) at an unacceptable 70%, improving little over the past 30 years. It is clear that continued adaption of current therapies will probably not improve these statistics and, for progress to be made, integration of biology with the design and implementation of future clinical trials is required. Indeed, advances in our understanding of the biology of ALCL are outstripping our ability to clinically translate them; laboratory-based research has highlighted a plethora of potential therapeutic targets but, with high survival rates combined with a scarcity of funding and patients to implement paediatric trials of novel agents, progress is slow. However, advances must be made to reduce the side-effects of intensive chemotherapy regimens whilst maintaining, if not improving, OS and EFS.

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“…Brentuximab vedotin, a CD30 monoclonal antibody linked to MMAE, has also been evaluated in adult patients with r/r B cell lymphomas with mixed results, including lower than anticipated response rates in patients with CD30+ PMBCL (Jacobsen et al , ; Bartlett et al , ; Zinzani et al , ). Safety data for the use of brentuximab in children is available from its evaluation in the treatment of patients with anaplastic large cell and Hodgkin lymphoma (Cole et al , ; Locatelli et al , ).…”

Section: Antibody‐based Therapymentioning

confidence: 99%

Mature B‐NHL in children, adolescents and young adults: current therapeutic approach and emerging treatment strategies

2019

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Mature B cell lymphomas account for approximately 60% of all cases of non-Hodgkin lymphoma (NHL) in children and adolescents and includes Burkitt lymphoma (BL), diffuse large B cell lymphoma (DLBCL) and other less common histologies. The outcome for patients treated with modern regimens in resource-intensive settings is excellent. Improvements in care have been accomplished through enhanced supportive therapy, including tumour lysis management and incremental refinement of chemotherapy backbones via cooperative group clinical trials in which patients receive risk group-specific intensive chemotherapy. More recent trials have established the safety and efficacy of immunotherapy. Ongoing work is required to address the substantial burden of acute therapy-related toxicity, as well as the identification of effective therapies for those patients with relapsed and refractory disease, for whom outcomes remain very poor. In this review we will summarize the results from recent therapeutic clinical trials, describe the evidence to support the inclusion of rituximab and review the rationale for the investigation of several new categories of novel agents for mature B cell lymphomas in children and adolescents.

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Brentuximab vedotin for paediatric relapsed or refractory Hodgkin's lymphoma and anaplastic large-cell lymphoma: a multicentre, open-label, phase 1/2 study

Cited by 83 publications

References 22 publications

Closing the survivorship gap in children and adolescents with Hodgkin lymphoma

Closing the survivorship gap in children and adolescents with Hodgkin lymphoma

From bench to bedside: the past, present and future of therapy for systemic paediatric ALCL, ALK+

Mature B‐NHL in children, adolescents and young adults: current therapeutic approach and emerging treatment strategies

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