Brentuximab vedotin with gemcitabine for paediatric and young adult patients with relapsed or refractory Hodgkin's lymphoma (AHOD1221): a Children's Oncology Group, multicentre single-arm, phase 1–2 trial

Cole, Peter D.; McCarten, Kathleen; Pei, Qinglin; Spira, Menachem; Metzger, Monika L.; Drachtman, Richard A.; Horton, Terzah M.; Bush, Rizvan; Blaney, Susan M.; Weigel, Brenda; Kelly, Kara M.

doi:10.1016/s1470-2045(18)30426-1

Cited by 72 publications

(75 citation statements)

References 33 publications

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“…A lower dose of BV (1.2 mg/kg) was given in this patient as a precaution for her decreased kidney function (eGFR before BV: 70 mL/min/1.73 m 2 ). Gemcitabine was added from the 6th until the 8th cycle of BV, as this combination has been reported by the AHOD1221 trial to result in positive outcome in pediatric and young adult patients with relapsed or refractory HL [9]. In this trial, 57% of all pediatric and young adult patients with relapsed or refractory HL achieved CR within the first 4 cycles of treatment, and 31% patients experienced PR or stable disease after 4 cycles (AHOD1221 trial) [9].…”

Section: Discussionmentioning

confidence: 99%

Complete Remission of Relapsed Hodgkin’s Lymphoma following Brentuximab Vedotin and Gemcitabine Combination Therapy with Severe Hypotension as Possible Treatment-Related Adverse Event: A Case Report

Purwanto¹,

Utomo²,

Ghozali³

2020

Case Rep Oncol

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A 40-year-old Asian female with heavily treated relapsed Hodgkin's lymphoma showed complete remission (CR) after receiving 8 cycles of brentuximab vedotin (BV) in combination with gemcitabine as 4th line treatment. The patient remained in CR at the 18-month post-treatment follow-up. She developed severe hypotension (50/36 mm Hg) with upper and lower limb petechiae and edema after the addition of gemcitabine on the 6th cycle of BV. This adverse event resolved after 3 days of treatment with vasopressor and high-dose corticosteroid. The addition of dexamethasone for the subsequent 2 cycles successfully prevented this adverse event from recurring.

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Section: Discussionmentioning

confidence: 99%

Complete Remission of Relapsed Hodgkin’s Lymphoma following Brentuximab Vedotin and Gemcitabine Combination Therapy with Severe Hypotension as Possible Treatment-Related Adverse Event: A Case Report

Purwanto¹,

Utomo²,

Ghozali³

2020

Case Rep Oncol

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“…All patients had a treatment‐emergent adverse event and 44% had at least one ≥grade 3 adverse event; 33% patients had transient, peripheral neuropathy. This paediatric experience with Bv contrasts with the phase II trial of Bv in combination with gemcitabine, where 67% (95% CI 51–80) of 42 evaluable patients had a complete response within the first four cycles of treatment (Cole et al , ). Four (31%) of 13 patients with a partial response or stable disease had all target lesions with Deauville scores of 3 or less after Cycle 4.…”

Section: Primary Prevention To Close the Survivorship Gapmentioning

confidence: 95%

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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“…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 with gemcitabine for paediatric and young adult patients with relapsed or refractory Hodgkin's lymphoma (AHOD1221): a Children's Oncology Group, multicentre single-arm, phase 1–2 trial

Abstract: National Institutes of Health and the St. Baldrick's Foundation.

Cited by 72 publications

References 33 publications

Complete Remission of Relapsed Hodgkin’s Lymphoma following Brentuximab Vedotin and Gemcitabine Combination Therapy with Severe Hypotension as Possible Treatment-Related Adverse Event: A Case Report

Complete Remission of Relapsed Hodgkin’s Lymphoma following Brentuximab Vedotin and Gemcitabine Combination Therapy with Severe Hypotension as Possible Treatment-Related Adverse Event: A Case Report

Closing the survivorship gap in children and adolescents with Hodgkin lymphoma

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

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