Approximately 30% of pediatric patients with anaplastic large cell lymphoma (ALCL) relapse. Although brentuximab vedotin has demonstrated excellent activity in ALCL, it has not been used for newly diagnosed patients. Children's Oncology Group (COG) trial ANHL12P1 determined the toxicity and efficacy of brentuximab vedotin with chemotherapy in children with newly diagnosed nonlocalized anaplastic large cell lymphoma kinase (ALK)+/CD30+ ALCL. From 2013 to 2017, 68 children with ALK+ ALCL were enrolled and received brentuximab vedotin. All patients received 5-day prophase, followed by 6 cycles of chemotherapy. Brentuximab vedotin was given on day 1 of each of the 6 cycles. Of the 67 patients eligible for toxicity evaluation, 66 completed all 6 cycles of chemotherapy, resulting in 399 evaluable cycles. There were no toxic deaths, no case of progressive multifocal leukoencephalopathy syndrome, and no case of grade 3 or 4 neuropathy. The 2-year event-free survival (EFS) was 79.1% (95% confidence interval [CI], 67.2-87.1). The 2-year overall survival (OS) was 97.0% (95% CI, 88.1-99.2). Fourteen patients relapsed. Eleven of 14 (79%) relapses occurred within 10 months of diagnosis; only 1 patient (1.5%) relapsed during therapy. Quantitative reverse transcription polymerase chain reaction for NPM-ALK at baseline (minimal disseminated disease) demonstrated prognostic value for EFS (P = .0004). Overall, the addition of brentuximab vedotin to standard chemotherapy does not add significant toxicity or alter the desired interval between cycles. The addition of brentuximab vedotin prevented relapses during therapy, and the OS and EFS estimates compare favorably with results obtained using conventional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01979536.
The CD30-directed antibody-drug conjugate brentuximab vedotin (BV) was FDA approved in 2011 for the treatment of relapsed classic Hodgkin lymphoma (cHL), in 2015 for maintenance after autologous transplantation in high-risk patients, and in 2018 for frontline therapy with doxorubicin, vinblastine, and dacarbazine for advanced stage cHL. Although the role of BV in cHL had been reasonably well-established, it is currently being challenged by the changing landscape of other highly effective novel agents, such as checkpoint inhibitor immunotherapies. In this review, we discuss the evolving role of BV in the management of cHL and ongoing studies attempting to define the optimal usage of this effective agent.
Hodgkin lymphoma (HL) is a rare hematologic malignancy with a bimodal distribution of incidence, with most patients diagnosed between the ages of 15 and 30 years and another peak in patients older than 55 years. It is estimated that in 2023, almost 9000 people were diagnosed with HL in the United States. Most patients will be cured using conventional chemotherapy and radiotherapy.
Peripheral T-cell lymphomas (PTCLs) are a heterogenous yet aggressive group of lymphomas that arise from mature T- or NK-cell precursors. Nodal PTCLs include anaplastic large-cell lymphoma, PTCL not otherwise specified, and follicular helper T-cell lymphomas. Recent advances in understanding these heterogenous diseases have prompted investigation of novel agents to improve on treatment.
Antibody-drug conjugates are a new class of cancer treatments that are becoming more widely used, but they come with various toxicities and complications that need to be managed, especially in emergencies.
Common side effects include diarrhea, nausea, rash, and peripheral neuropathy, while severe conditions like interstitial lung disease and sinusoidal obstruction syndrome can pose serious health risks.
Rare but critical issues include cardiac effects, ocular problems, and tumor lysis syndrome, which require careful monitoring and prompt medical intervention.
