Julia Meissner, Sascha Dietrich, Anna Sureda, Herve Finel, Irma Khvedelidze, Luca Castagna, Noël Milpied, Herve Ghesquieres, Ron Ram, Ali Bazarbachi, Roch Houot, Georg Maschmeyer, Domenico Russo, Jakob Passweg, Alexandros Spyridonidis, Michael Stadler, Stephen Robinson, Peter Dreger, Silvia Montoto
Lymphoma Working Party, European Society for Blood and Marrow Transplantation
Background: Hodgkin lymphoma (HL) patients who relapse or progress after alloSCT have a dismal prognosis and limited treatment options. Treatment with monoclonal antibodies (mAbs) targeting the programmed cell death receptor (PD-1) show impressive clinical activity in relapsed/refractory HL, but the use of anti-PD-1 mAbs after alloSCT might be associated with initiation or reactivation of graft-versus-host disease (GVHD).
Methods: We conducted a registry-based retrospective multicenter study on patients aged 18 years or above, with histologically verified HL who received PD-1 blockade treatment for relapse of HL after alloSCT.
Results: A complete data set with information on anti-PD-1 treatment could be retrieved from the EBMT database for 20. The median age at treatment with anti-PD-1 mAbs was 31.5 (range 20–75) years. HL patients received a median of 4 prior lines of treatment before alloSCT (range 2–7) and 18 patients had undergone prior autologous stem cell transplantation. The median time from alloSCT to relapse was 12 (95% confidence interval 6.8–20.3) months, and the median time from alloSCT to start of PD-1 blockade was 21 (95% confidence interval 19–41) months. All patients received nivolumab, which was given for a median of 12 (range 1–37) cycles. Upon treatment with nivolumab, 10 patients achieved a complete remission (CR, 50%, PET-confirmed in 6 of 10 patients), and 9 patients a partial remission (PR, 45%) resulting in an overall response rate (ORR) of 95%. The median time to best response was 4.3 (95% confidence interval: 2.9–11) months. Two of 20 patients (10%) died, due to a fungal pneumonia 2.3 months after last nivolumab treatment, and a steroid refractory acute GVHD, respectively. Upon PD-1 blocking treatment, an episode of aGVHD occurred in four of 18 (22%) assessable patients. GVHD occurred in all patients after the first dose of nivolumab (after a median interval of 6 days, range 2–10 days). Two of these patients had experienced a previous episode of aGVHD or cGVHD, respectively. Acute GVHD led to nivolumab discontinuation in 2 of 4 patients. One of these patients died in CR from steroid-refractory grade 3–4 aGVHD 2.8 months after nivolumab. Remaining GVHD episodes after Nivolumab were steroid-sensitive.
Conclusion: In line with other reports, this study confirms that treatment with CI that target the PD-1 receptor can be safely administered to patients with HL relapse after an alloSCT and this results in good tumor responses.