Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma.

Affiliation

Merryman RW(#)(1), Castagna L(#)(2), Giordano L(2), Ho VT(3), Corradini P(4), Guidetti A(4), Casadei B(5), Bond DA(6), Jaglowski S(6), Spinner MA(7), Arai S(7), Lowsky R(7), Shah GL(8), Perales MA(8), De Colella JMS(9), Blaise D(10), Herrera AF(11), Shouse G(11), Spilleboudt C(12), Ansell SM(13), Nieto Y(14), Badar T(15), Hamadani M(16), Feldman TA(17), Dahncke L(17), Singh AK(18), McGuirk JP(18), Nishihori T(19), Chavez J(19), Serritella AV(20), Kline J(20), Mohty M(21), Dulery R(22), Stamatoulas A(22), Houot R(23), Manson G(23), Moles-Moreau MP(24), Orvain C(24), Bouabdallah K(25), Modi D(26), Ramchandren R(27), Lekakis L(28), Beitinjaneh A(28), Frigault MJ(29), Chen YB(29), Lynch RC(30), Smith SD(30), Rao U(31), Byrne M(31), Romancik JT(32), Cohen JB(32), Nathan S(33), Phillips T(34), Joyce RM(35), Rahimian M(35), Bashey A(36), Ballard HJ(37), Svoboda J(37), Torri V(38), Sollini M(39), De Philippis C(2), Magagnoli M(2), Santoro A(2), Armand P(#)(3), Zinzani PL(#)(5)(39), Carlo-Stella C(#)(2)(40).
Author information:
(1)Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. [Email]
(2)Department of Oncology and Hematology, Humanitas Clinical and Research Center-IRCCS, Rozzano-Milano, Italy.
(3)Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
(4)Division of Hematology and Bone Marrow Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Milano, Milano, Italy.
(5)Istituto di Ematologia "Seràgnoli", Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università Degli Studi, Bologna, Italia.
(6)Division of Hematology, The Ohio State University, Columbus, OH, USA.
(7)Department of Medicine, Stanford University Medical Center, Stanford, CA, USA.
(8)Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
(9)Programme de Transplantation & Therapie Cellulaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, Marseille, France.
(10)Institut Paoli-Calmettes, Aix Marseille University, CNRS, INSERM, CRCM, Marseille, France.
(11)Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
(12)Service Hématologie, Institut Bordet, Bruxelles, Belgium.
(13)Division of Hematology, Mayo Clinic, Rochester, MN, USA.
(14)Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
(15)Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USA.
(16)BMT & Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
(17)John Theurer Cancer Center at HMH, Hackensack Meridian Health School of Medicine, Hackensack, NJ, USA.
(18)Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS, USA.
(19)Department of Blood & Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, USA.
(20)Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA.
(21)Service d'Hématologie Clinique et de Thérapie Cellulaire, Hospital Saint Antoine, Sorbonne University, Paris, France.
(22)Department of Hematology, Centre Henri Becquerel, Rouen, France.
(23)Department of Hematology, CHU Rennes, University of Rennes, Inserm U1236, Rennes, France.
(24)CHU Angers, Angers, France.
(25)Hematology Clinic, University Hospital of Bordeaux, Pessac, France.
(26)Department of Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA.
(27)Division of Hematology/Oncology, University of Tennessee School of Medicine, Knoxville, TN, USA.
(28)Division of Transplantation and Cellular Therapy, University of Miami/Sylvester Cancer Center, Miami, FL, USA.
(29)Blood and Marrow Transplant Program, Massachusetts General Hospital, Boston, MA, USA.
(30)University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
(31)Department of Medicine, Division of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.
(32)Emory University Winship Cancer Institute, Atlanta, GA, USA.
(33)Section of Bone Marrow Transplant and Cell Therapy, Rush University Medical Center, Chicago, IL, USA.
(34)Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA.
(35)Division of Hematologic Malignancy, Beth Israel Deaconess Medical Center, Boston, MA, USA.
(36)Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA.
(37)Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
(38)Laboratory of Methodology of Clinical Research, Oncology Department. IRCCS Mario Negri Institute, Milano, Italy.
(39)Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italia.
(40)Department of Biomedical Sciences, Humanitas University, Rozzano-Milan, Italy.
(#)Contributed equally

Abstract

Anti-PD-1 monoclonal antibodies yield high response rates in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but most patients will eventually progress. Allogeneic hematopoietic cell transplantation (alloHCT) after PD-1 blockade may be associated with increased toxicity, raising challenging questions about the role, timing, and optimal method of transplantation in this setting. To address these questions, we assembled a retrospective cohort of 209 cHL patients who underwent alloHCT after PD-1 blockade. With a median follow-up among survivors of 24 months, the 2-year cumulative incidences (CIs) of non-relapse mortality and relapse were 14 and 18%, respectively; the 2-year graft-versus-host disease (GVHD) and relapse-free survival (GRFS), progression-free survival (PFS), and overall survival were 47%, 69%, and 82%, respectively. The 180-day CI of grade 3-4 acute GVHD was 15%, while the 2-year CI of chronic GVHD was 34%. In multivariable analyses, a longer interval from PD-1 to alloHCT was associated with less frequent severe acute GVHD, while additional treatment between PD-1 and alloHCT was associated with a higher risk of relapse. Notably, post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis was associated with significant improvements in PFS and GRFS. While awaiting prospective clinical trials, PTCy-based GVHD prophylaxis may be considered the optimal transplantation strategy for this patient population.