PET-Adapted Sequential Salvage Therapy With Brentuximab and Augmented ICE Produces High Response Rate in Relapsed/Refractory Hodgkin Lymphoma
In a phase II study reported in The Lancet Oncology, Moskowitz et al found that a salvage strategy involving brentuximab vedotin (Adcetris) treatment followed by 18F-fluorodeoxyglucose positron-emission tomography (PET) and augmented ifosfamide, carboplatin, and etoposide (ICE) in PET-positive patients resulted in a high rate of PET-negative status in patients with relapsed/refractory Hodgkin lymphoma.
Study Details
The study included 45 patients with relapsed/refractory disease and failure of one previous doxorubicin-containing regimen who were enrolled between January 2012 and October 2013 at Memorial Sloan Kettering Cancer Cancer. Patients received weekly infusions of brentuximab vedotin at 1.2 mg/kg on days 1, 8, and 15 in two 28-day cycles and then underwent PET scan.
Those with PET-negative status (Deauville score of 1 or 2) immediately underwent high-dose therapy and autologous stem cell transplantation. Those with persistent PET abnormalities received two cycles of augmented ICE consisting of two doses of ifosfamide at 5,000 mg/m2 in combination with mesna at 5,000 mg/m2 via continuous infusion over 24 hours on days 1 and 2, one dose of carboplatin at AUC 5 on day 3, and three doses of etoposide at 200 mg/m2 every 12 hours on day 1 before being considered for high-dose therapy/autologous stem cell transplantation.
PET-Negative Status
PET-negative status was achieved in 12 patients (27%) after brentuximab vedotin treatment, with all proceeding to high-dose therapy/autologous stem cell transplantation. Of 32 evaluable patients receiving augmented ICE, PET-negative status was achieved in 22 (69%). Overall, 34 (76%) of 45 patients achieved PET-negative status, and all 44 patients who completed protocol treatment received high-dose therapy/autologous stem cell transplantation.
The most common adverse events of any grade associated with brentuximab treatment were hyperglycemia (68%), fatigue (67%), and rash (58%), and the most common grade 3 or 4 events were hyperglycemia (4%), hypoglycemia (4%), and hypocalcemia (4%).
The investigators concluded: “PET-adapted sequential salvage therapy with brentuximab vedotin followed by [augmented] ICE resulted in a high proportion of patients with relapsed or refractory Hodgkin’s lymphoma achieving PET-negativity, and therefore could optimise the chance of cure after [high-dose therapy/autologous stem cell transplantation].”
Alison J. Moskowitz, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for The Lancet Oncology article.
The study was funded by Seattle Genetics. For full disclosures of the study authors, visit www.thelancet.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
