Immune checkpoint inhibitors in combination with radiotherapy as salvage treatment for relapsed/refractory classical Hodgkin lymphoma: A retrospective analysis in 12 patients.

Elisa Lucchini,Anna Di Russo,Francesca Ricci,Anna Schiattarella,Stefano Volpetti,Umberto Ricardi,Armando Santoro,Manuela Caizzi,Fabio Matrone,Francesco Zaja,Mario Levis,Chiara Rusconi

doi:10.4081/hr.2021.9080

Abstract

The rate of complete remission (CR) with the anti-PD1 immune checkpoint inhibitors (ICI) nivolumab (N) and pembrolizumab (P) in patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) is low (20-30%), and the majority of patients eventually relapse. One strategy to improve their outcome is to combine ICI with radiotherapy (ICI-RT), taking advantage of a supposed synergistic effect. We retrospectively collected data of 12 adult patients with R/R cHL treated with ICI-RT delivered during or within 8 weeks from the start or after the end of ICI. Median age at ICI-RT was 37 years, 50% had previously received an autologous stem cell transplantation (SCT) and 92% brentuximab vedotin. RT was given concurrently, before or after ICI in 4, 1 and 7 patients. Median RT dose was 30Gy, for a median duration of 22 days. Median number of ICI administrations was 15. Overall response and CR rate were 100% and 58%. Nine patients received subsequent SCT consolidation (7 allogeneic and 2 autologous). After a median follow-up of 18 months, 92% of patients were in CR. No major concerns about safety were reported. ICI-RT combination appears to be a feasible and highly active bridge treatment to transplant consolidation.

Highlights

Contributions: FZ and UR designed the study; EL and ML wrote the manuscript
In this report we describe the clinical characteristics and the outcomes of a group of R/R classical Hodgkin lymphoma (cHL) patients who were treated with immune checkpoint inhibitors (ICI) in combination with RT
The majority of patients (83%) received ICI with radiotherapy (ICI-RT) as the Outcomes risk group in 58%

Summary

Introduction

Contributions: FZ and UR designed the study; EL and ML wrote the manuscript. All the authors contributed to data collection and dataBefore the era of immunotherapy, the prognosis of patients with relapsed/refractoanalysis, critically revised the manuscript and approved the final version of the paper.Isontina, Trieste; 2Division of ry (R/R) classical Hodgkin LymphomaHematology and Stem CellTransplantation Fondazione IRCCS ly Istituto Nazionale dei Tumori, Milano; n 3Department of Oncology, University of o Torino; 4Department of Oncology and Hematology, Humanitas Clinical and e Research Center - IRCCS, Rozzano, s Milano; 5Department of Hematology, u Azienda Sanitaria Universitaria Friuli l Centrale, Udine; 6Department of ia Radiation Oncology, Centro di Riferimento Oncologico di Aviano c (CRO) IRCCS, Aviano, Pordenone; r 7Division of Radiotherapy Oncology e Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; 8Department of m Radiotherapy, Azienda Sanitaria m Universitaria Giuliano-Isontina, Trieste; o 9Department of Medical, Surgical and Health Sciences, University of Trieste,-c Italy Non Abstract (cHL) who fail salvage therapy and autologous stem cell transplantation (SCT) consolidation was poor with an estimated median overall survival of 2 years.[1,2] In the last few years, the introduction of Brentuximab Vedotin (BV) and immune checkpoint inhibitors (ICI) has offered new therapeutic opportunities for patients with R/R cHL.BV single agent results in 75% overall response rate (ORR) in the R/R setting, but most patients require further treatment within 1 year.[3]. Contributions: FZ and UR designed the study; EL and ML wrote the manuscript. Transplantation Fondazione IRCCS ly Istituto Nazionale dei Tumori, Milano; n 3Department of Oncology, University of o Torino; 4Department of Oncology and Hematology, Humanitas Clinical and e Research Center - IRCCS, Rozzano, s Milano; 5Department of Hematology, u Azienda Sanitaria Universitaria Friuli l Centrale, Udine; 6Department of ia Radiation Oncology, Centro di Riferimento Oncologico di Aviano c (CRO) IRCCS, Aviano, Pordenone; r 7Division of Radiotherapy Oncology e Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; 8Department of m Radiotherapy, Azienda Sanitaria m Universitaria Giuliano-Isontina, Trieste; o 9Department of Medical, Surgical and Health Sciences, University of Trieste,. BV single agent results in 75% overall response rate (ORR) in the R/R setting, but most patients require further treatment within 1 year.[3] The ICI Nivolumab (N) and Pembrolizumab (P) bind to PD-1 protein expressed by T cells, inhibiting the binding with PD1-ligand (PD-L1).

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