PET-adapted sequential salvage therapy with brentuximab vedotin followed by augmented ifosamide, carboplatin, and etoposide for patients with relapsed and refractory Hodgkin's lymphoma: a non-randomised, open-label, single-centre, phase 2 study. Issue 3 (March 2015)

• Record Type: Journal Article
• Authors: Moskowitz, Alison J; Schöder, Heiko; Yahalom, Joachim; McCall, Susan J; Fox, Stephanie Y; Gerecitano, John; Grewal, Ravinder; Hamlin, Paul A; Horwitz, Steven; Kobos, Rachel; Kumar, Anita; Matasar, Matthew; Noy, Ariela; Palomba, M Lia; Perales, Miguel-Angel; Portlock, Carol S; Sauter, Craig; Shukla, Neerav; Steinherz, Peter; Straus, David; Trippett, Tanya; Younes, Anas; Zelenetz, Andrew; Moskowitz, Craig H
• Is Part Of: Lancet oncology. Volume 16:Issue 3(2015:Mar.)
• Page Start: 284
• Page End: 292
• Publication Date: 2015-03
• Subjects: Oncology -- Periodicals; Neoplasms -- Periodicals; Cancérologie -- Périodiques; Oncologie; Oncology; Periodicals; Electronic journals; 616.994005
• DOI: 10.1016/S1470-2045(15)70013-6
• Languages: English
• ISSNs: 1470-2045

Abstract

<abstract abstract-type="author" id="ceab10"> <title id="cestitle10">Summary</title> <sec> <title id="cestitle20">Background</title> <p id="spara170">Pre-transplantation <sup>18</sup>F-fluorodeoxyglucose (FDG) PET-negativity is one of the strongest predictors of outcome after high-dose therapy and autologous stem-cell transplant (HDT/ASCT) for patients with relapsed or refractory Hodgkin's lymphoma. In this study, we assessed the feasibility and activity of PET-adapted salvage therapy with brentuximab vedotin, followed by augmented ifosfamide, carboplatin, and etoposide (ICE).</p> </sec> <sec> <title id="cestitle30">Methods</title> <p id="spara180">In this non-randomised, open-label, single-centre, phase 2 trial, we enrolled patients with relapsed or refractory Hodgkin's lymphoma who had failed one previous doxorubicin-containing chemotherapy regimen. All patients received weekly infusions of 1·2 mg/kg brentuximab vedotin on days 1, 8, and 15 for two 28 day cycles. After completion of brentuximab vedotin treatment, patients received a PET scan. Patients who achieved PET-negative status (a Deauville score of 1 or 2) proceeded directly to HDT/ASCT; those with persistent abnormalities on PET received two cycles of augmented ICE (augICE; two doses of ifosfamide 5000 mg/m<sup>2</sup> in combination with mesna 5000 mg/m<sup>2</sup> continuous infusion over 24 h, days 1 and 2; one dose of carboplatin AUC 5, day 3; three doses of etoposide 200 mg/m<sup>2</sup> every 12 h, day 1) before consideration for HDT/ASCT. Only patients with persistent abnormalities on PET after brentuximab vedotin received augICE; however, all patients in the intention-to-treat population were assessed for the primary outcome, which was the proportion of patients who were PET-negative after brentuximab vedotin alone or brentuximab vedotin followed by augICE. This study is registered with <ext-link ext-link-type="unknown" id="interrefs10" xlink:type="simple" xlink:href="http://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link>, number <ext-link ext-link-type="unknown" id="interrefs20" xlink:type="simple" xlink:href="ctgov:NCT01508312" xmlns:xlink="http://www.w3.org/1999/xlink">NCT01508312</ext-link>, and is no longer accruing patients.</p> </sec> <sec> <title id="cestitle40">Findings</title> <p id="spara190">Between Jan 5, 2012, and Oct 4, 2013, we enrolled 46 patients. One patient was deemed ineligible, and not evaluable, before treatment initiation owing to having nodular, lymphocyte-predominant Hodgkin's lymphoma and thus 45 patients received treatment. After brentuximab vedotin, 12 patients (27%, 95% CI 13–40) were PET-negative and proceeded to HDT/ASCT. 33 (73%, 95% CI 60–86) patients were PET-positive after brentuximab vedotin; one PET-positive patient withdrew consent, therefore 32 PET-positive patients received augICE, 22 (69%, 95% CI 53–85) of whom were PET-negative. Overall, 34 patients (76%, 95% CI 62–89) achieved PET-negativity. All 44 patients who completed treatment as per protocol proceeded to receive HDT/ASCT. Brentuximab vedotin was well tolerated and associated with few grade 3–4 adverse events including hyperglycaemia (two [4%] patients, grade 3), nausea (one [2%], grade 3), hypoglycaemia (one [2%], grade 3 and one [2%], grade 4), and hypocalcaemia (one [2%], grade 3 and one [2%], grade 4).</p> </sec> <sec> <title id="cestitle50">Interpretation</title> <p id="spara200">PET-adapted sequential salvage therapy with brentuximab vedotin followed by augICE 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 HDT/ASCT.</p> </sec> <sec> <title id="cestitle60">Funding</title> <p id="spara210">Seattle Genetics.</p> </sec> </abstract>