Combining brentuximab vedotin with dexamethasone, high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma: the phase II HOVON/LLPC Transplant BRaVE study
Marie José Kersten,
Julia Driessen,
Josée M. Zijlstra,
Wouter J. Plattel,
Franck Morschhauser,
Pieternella J. Lugtenburg,
Pauline Brice,
Martin Hutchings,
Thomas Gastinne,
Roberto Liu,
Coreline N. Burggraaff,
Marcel Nijland,
Sanne H. Tonino,
Anne I.J. Arens,
Roelf Valkema,
Harm van Tinteren,
Marta Lopez-Yurda,
Arjan Diepstra,
Daphne De Jong,
Anton Hagenbeek
Affiliations
Marie José Kersten
Dept of Hematology, Amsterdam UMC, University of Amsterdam, and LYMMCARE, Amsterdam, The Netherlands;
Julia Driessen
Dept of Hematology, Amsterdam UMC, University of Amsterdam, and LYMMCARE, Amsterdam, The Netherlands;
Josée M. Zijlstra
Dept of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands;
Wouter J. Plattel
Dept of Hematology, University of Groningen, UMC Groningen, Groningen, The Netherlands;
Franck Morschhauser
Dept of Hematology, Centre Hospitalier Universitaire, Lille, France;
Pieternella J. Lugtenburg
Dept of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands;
Pauline Brice
Dept of Hematology, Hopital Saint Louis, Paris, France;
Martin Hutchings
Dept of Hematology, Rigshospitalet, Copenhagen, Denmark;
Thomas Gastinne
Dept of Hematology, Centre Hospitalier Universitaire, Nantes, France;
Roberto Liu
Dept of Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands;
Coreline N. Burggraaff
Dept of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands;
Marcel Nijland
Dept of Hematology, University of Groningen, UMC Groningen, Groningen, The Netherlands;
Sanne H. Tonino
Dept of Hematology, Amsterdam UMC, University of Amsterdam, and LYMMCARE, Amsterdam, The Netherlands;
Anne I.J. Arens
Dept of Radiology and Nuclear Medicine, Radboud university medical center, Nijmegen, The Netherlands;
Roelf Valkema
Dept of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands;
Harm van Tinteren
Dept of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands;
Marta Lopez-Yurda
Dept of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands;
Arjan Diepstra
Dept. of Pathology and Medical Biology, UMC Groningen, University of Groningen, the Netherlands;
Daphne De Jong
Dept of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Anton Hagenbeek
Dept of Hematology, Amsterdam UMC, University of Amsterdam, and LYMMCARE, Amsterdam, The Netherlands;
Achieving a metabolic complete response (mCR) before high-dose chemotherapy (HDC) and autologous peripheral blood stem-cell transplant (auto-PBSCT) predicts progression free survival (PFS) in relapsed/refractory classical Hodgkin lymphoma (R/R cHL). We added brentuximab vedotin (BV) to DHAP to improve the mCR rate. In a Phase I dose-escalation part in 12 patients, we showed that BV-DHAP is feasible. This Phase II study included 55 R/R cHL patients (23 primary refractory). Treatment consisted of three 21-day cycles of BV 1.8 mg/kg on day 1, and DHAP (dexamethasone 40mg days 1-4, cisplatin 100mg/m2; day 1 and cytarabine 2x2g/m2; day 2). Patients with a metabolic partial response (mPR) or mCR proceeded to HDC/auto-PBSCT. Based on independent central FDG-PET-CT review, 42 of 52 evaluable patients (81% [95% CI: 67-90]) achieved an mCR before HDC/auto-PBSCT, five had an mPR and five had progressive disease (three were not evaluable). After HDC/auto-PBSCT, four patients with an mPR converted to an mCR. The 2-year PFS was 74% [95% CI: 63-86], and the overall survival 95% [95% CI: 90-100]. Toxicity was manageable and mainly consisted of grade 3/4 hematological toxicity, fever, nephrotoxicity, ototoxicity (grade 1/2) and transiently elevated liver enzymes during BV-DHAP. Eighteen patients developed new onset peripheral neuropathy (maximum grade 1/2) and all recovered. In conclusion, BV-DHAP is a very effective salvage regimen in R/R cHL patients, but patients should be monitored closely for toxicity. ClinicalTrials.gov identifier: NCT02280993.
