Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma

Reid Merryman (1) , Luca Castagna (2) , Laura Giordano (2) , Vincent Ho (1) , Paolo Corradini (3) , Anna Guidetti (3) , Beatrice Casadei (4) , David Bond (5) , Samantha Jaglowski (5) , Michael Spinner (6) , Sally Arai (6) , Robert Lowsky (6) , Gunjan Shah (7) , Miguel-Angel Perales (7) , Jean Marc Schiano de Colella (8) , Didier Blaise (8) , Alex Herrera , Geoffrey Shouse , Chloe Spilleboudt (9) , Stephen Ansell , Yago Nieto , Talha Badar , Mehdi Hamadani , Tatyana Feldman , Lori Dahncke , Anurag Singh , Joseph Mcguirk , Taiga Nishihori , Julio Chavez , Anthony Serritella , Justin Kline , Mohamad Mohty (10) , Remy Dulery (11) , Aspasia Stamatoulas (11) , Roch Houot (12, 13) , Guillaume Manson (12, 13) , Marie-Pierre Moles-Moreau (14) , Corentin Orvain (14) , Kamal Bouabdallah (15) , Dipenkumar Modi , Radhakrishnan Ramchandren , Lazaros Lekakis , Amer Beitinjaneh , Matthew Frigault , Yi-Bin Chen , Ryan Lynch , Stephen Smith , Uttam Rao , Michael Byrne , Jason Romancik , Jonathon Cohen , Sunita Nathan , Tycel Phillips , Robin Joyce , Maryam Rahimian , Asad Bashey , Hatcher Ballard , Jakub Svoboda , Valter Torri , Martina Sollini , Chiara de Philippis , Massimo Magagnoli , Armando Santoro , Philippe Armand (1) , Pier Luigi Zinzani (4) , Carmelo Carlo-Stella (2, 16)

1 Dana-Farber Cancer Institute [Boston]
2 Humanitas Clinical and Research Center [Rozzano, Milan, Italy]
3 UNIMI - Università degli Studi di Milano = University of Milan
4 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
5 OSU - Ohio State University [Columbus]
6 Stanford University
7 Memorial Sloane Kettering Cancer Center [New York]
8 IPC - Institut Paoli-Calmettes
9 Institut Jules Bordet [Bruxelles]
10 CHU Saint-Antoine [AP-HP]
11 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
12 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
13 MICMAC - Microenvironment, Cell Differentiation, Immunology and Cancer
14 CHU Angers - Centre Hospitalier Universitaire d'Angers
15 CHU Bordeaux
16 Hunimed - Humanitas University [Milan]

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.

Domaines: Sciences du Vivant [q-bio]

Reid Merryman, Luca Castagna, Laura Giordano, Vincent Ho, Paolo Corradini, et al.. Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma. Leukemia, 2021, 35 (9), pp.2672-2683. ⟨10.1038/s41375-021-01193-6⟩. ⟨hal-03229516⟩