Brentuximab vedotin plus chemotherapy produced an overall survival rate of 98.7% after 3.4 years.

  • Major Finding: Brentuximab vedotin plus chemotherapy produced an overall survival rate of 98.7% after 3.4 years.

  • Concept: This antibody–drug conjugate reduced the need for radiotherapy relative to that in prior trials.

  • Impact: Brentuximab vedotin may enable prevention of some radiation-linked late-occurring adverse events.

The prognosis for pediatric patients with classic Hodgkin lymphoma, even the high-risk subtype, is favorable; however, treatment requires chemotherapy and radiotherapy that may cause adverse events in the long term. In an open-label, single-arm clinical trial enrolling 77 pediatric patients with high-risk Hodgkin lymphoma, Metzger and colleagues evaluated the use of the CD30-targeting antibody–drug conjugate brentuximab vedotin in place of vincristine in standard OEPA or COPDac (vincristine plus etoposide, prednisone, and doxorubicin or cyclophosphamide plus vincristine, prednisone, and dacarbazine, respectively) therapy to determine whether brentuximab vedotin, which is approved for adults with the same malignancy, could reduce the use of radiotherapy. Following brentuximab vedotin and chemotherapy treatment, only lymph nodes that did not exhibit a complete response at the early response assessment were irradiated. After a median follow-up period of 3.4 years, the event-free survival rate was 97.4% (75 of 77 patients) and the overall survival rate was 98.7% (76 of 77 patients). The death occurred unexpectedly due to ventricular tachycardia during cycle 4 of chemotherapy, suggesting that monitoring for this condition is warranted, but the treatment regimen otherwise had an adverse event profile similar to that expected given the individual therapies administered. Notably, the nodal responses allowed for radiotherapy to be omitted in 35% (27 of 77 patients) of treated patients, and the exposure of normal tissue to radiation was substantially reduced relative to exposures in a prior trial by the same group that enrolled a similar patient population. In summary, the results of this study provide evidence that the substitution of brentuximab vedotin for vincristine in standard OEPA or COPDac is safe and effective and that this treatment regimen may enable reduced use of radiotherapy, potentially preventing late-occurring adverse events owing to radiation exposure.

Metzger ML, Link MP, Billett AL, Flerlage J, Lucas Jr JT, Mandrell BN, et al. Excellent outcome for pediatric patients with high-risk Hodgkin lymphoma treated with brentuximab vedotin and risk-adapted residual node radiation. J Clin Oncol 2021 Apr 7 [Epub ahead of print].

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