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Letters to the Editor
Figure 1. Efficacy of anti-PD1 re-treatment.
received a salvage therapy with GVD (gemcitabine, vinorelbine, and pegylated liposomal doxorubicin) fol- lowed by ibrutinib without efficacy. At progression, he received a reduced dose of nivolumab (total dose of 30 mg) which induced a GvHD flare. The patient further experienced two disease progressions which were treated with two additional infusions of low dose nivolumab (10 mg) which resulted again in GvHD flares. These sequential treatments induced transient lymphoma regression, with PR as the best response.
The GvHD flares observed in this patient are not unexpected. Indeed, prior studies have reported that anti-PD1 therapy potentially induces GvHD reactiva- tion in patients that previously underwent alloSCT.2,3 Anti-PD1 re-treatment did not induce other significant toxicities in the other patients.
There is only limited data regarding the efficacy of re- challenge with anti-PD1 antibodies in cancer patients. Only a few cases have been reported in patients with solid tumors, namely in non-small cell lung cancer4 and melanoma.5 However, most of these patients had failed initial anti-PD1 therapy and received chemotherapy prior to anti-PD1 re-treatment. This is in contrast to our study in which all patients were sensitive to initial anti- PD1 therapy and were responsive (CR or PR) at the time of discontinuation.
At the ISHL11 meeting, Ansell et al. reported in an abstract the efficacy of anti-PD1 re-treatment in five patients who achieved remission upon nivolumab but relapsed after treatment discontinuation.4 All patients responded to nivolumab re-treatment (one CR and four PR).6 Recently, Chen et al. reported an update of the KEYNOTE-087 study after 2 years of follow-up.7 This study evaluated pembrolizumab in R/R HL. In a subset analysis, Chen et al. reported the outcome of 10 patients who received a second course of pembrolizumab after anti-PD1 discontinuation. Eight patients were evaluable and six of them (75%) experienced an objective response upon re-treatment with pembrolizumab (four CR and two PR). The study neither reported on the effi- cacy of the first course of anti-PD1, the reasons for anti- PD1 discontinuation nor the tumor status at anti-PD1
discontinuation in these patients. Nevertheless, the study shows that most patients responded to anti-PD1 re-treatment.
Our study, along with the studies recently published by Ansell et al.6 and Chen et al.,7 are the first to report on the efficacy of anti-PD1 re-treatment in anti-PD1 sensi- tive, R/R HL patients who relapsed/progressed after anti-PD1 discontinuation. These two studies show high response rates (75-100%) after anti-PD1 re-treatment suggesting that these patients usually remain “anti-PD1 sensitive” at relapse. These observations suggest that anti-PD1 is an effective salvage therapy for HL patients who relapse after anti-PD1 discontinuation. Larger stud- ies are warranted to confirm these results.
Guillaume Manson,1 Pauline Brice,2 Charles Herbaux,3 Kamal Bouabdallah,4 Chloé Antier,5 Florence Poizeau,6,7 Laurent Dercle8-10 and Roch Houot1
1Department of Hematology, University Hospital of Rennes,
2
Rennes, France; Department of Hematology, Saint-Louis
Hospital, AP-HP, Paris, France; 3Department of Hematology, University Hospital of Lille, Lille, France; 4Department of Hematology, University Hospital of Bordeaux, Bordeaux, France; 5Department of Hematology, Nantes University Hospital, Nantes, France; 6Department of Dermatology, University hospital of Rennes, Rennes, France; 7EA 7449 REPERES (Pharmacoepidemiology and Health Services Research), Rennes 1 University, Rennes, France; 8Medical Imaging Department, Institut Gustave Roussy, Villejuif, France; 9UMR1015, Institut Gustave Roussy, Villejuif, France and 10Department of Radiology, Columbia University Medical Center, New York, NY, USA
Correspondence:
ROCH HOUOT - roch.houot@chu-rennes.fr
doi:10.3324/haematol.2019.242529
References
1. Manson G, Herbaux C, Brice P, et al. Prolonged remissions after anti-PD-1 discontinuation in patients with Hodgkin lymphoma. Blood. 2018;131(25):2856-2859.
2. Haverkos BM, Abbott D, Hamadani M, et al. PD-1 blockade for relapsed lymphoma post–allogeneic hematopoietic cell trans- plant: high response rate but frequent GVHD. Blood.
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