Phase II Trial of Pembrolizumab Plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin as Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma
Alison J. Moskowitz, Gunjan L. Shah, Heiko Schöder, Nivetha Ganesan, Esther Drill, Helen Hancock, Theresa Davey, Leslie Perez, Sun-Young Ryu, Samia Sohail, Alayna Santarosa, Natasha Galasso, Rachel Neuman, Brielle Liotta, William Blouin, Anita Kumar, Oscar Lahoud, Connie Lee Batlevi, Paul A. Hamlin, David J. Straus, Ildefonso Rodriguez-Rivera, Colette Owens, Philip Caron, Andrew M. Intlekofer, Audrey Hamilton, Steven M. Horwitz, Lorenzo Falchi, Erel Joffe, W. Thomas Johnson, Christina Y. Lee, M. Lia Palomba, Ariela Noy, Matthew J. Matasar, Georgios Pongas, Gilles Salles, Santosha A. Vardhana, Beatriz Wills Sanín, Gottfried von Keudell, Joachim Yahalom, Ahmet Doǧan, Andrew D. Zelenetz, Craig H. Moskowitz
Abstract
PURPOSE: We conducted a phase II study evaluating pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD) as second-line therapy for relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) (ClinicalTrials.gov identifier: NCT03618550). METHODS: , days 1 and 8), given on 21-day cycles. The primary end point was complete response (CR) following up to four cycles of pembro-GVD. Patients who achieved CR by labeled fluorodeoxyglucose-positron emission tomography (Deauville ≤ 3) after two or four cycles proceeded to high-dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). HDT/AHCT was carried out according to institutional standards, and brentuximab vedotin maintenance was allowed following HDT/AHCT. RESULTS: Of 39 patients enrolled, 41% had primary ref disease and 38% relapsed within 1 year of frontline treatment. 31 patients received two cycles of pembro-GVD, and eight received four cycles. Most adverse events were grade 1 or two, whereas few were grade 3 and included transaminitis (n = 4), neutropenia (n = 4), mucositis (n = 2), thyroiditis (n = 1), and rash (n = 1). Of 38 evaluable patients, overall and CR rates after pembro-GVD were 100% and 95%, respectively. Thirty-six (95%) patients proceeded to HDT/AHCT, two received pre-HDT/AHCT involved site radiation, and 13 (33%) received post-HDT/AHCT brentuximab vedotin maintenance. All 36 transplanted patients are in remission at a median post-transplant follow-up of 13.5 months (range: 2.66-27.06 months). CONCLUSION: Second-line therapy with pembro-GVD is a highly effective and well-tolerated regimen that can efficiently bridge patients with rel/ref cHL to HDT/AHCT.