Chiara de Philippis, Jacopo Mariotti, Stefania Bramanti, Barbara Sarina, Massimo Magagnoli, Lucia Morello, Armando Santoro, Carmelo Carlo-Stella and Luca Castagna
Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano, Italy
Immune checkpoint inhibition by monoclonal antibodies before allogeneic stem cell transplantation (allo-SCT) could enhance allogeneic T-cell responses.
We retrospectively analyzed outcomes of 27 Hodgkin Lymphoma (HL) patients undergoing allo-SCT after nivolumab at Humanitas Cancer Center between 2015 and 2018. The aim was to focus on early toxicities (occurring until day +100). Patients’ characteristics are listed in Table 1.
Acute Graft Versus Host Disease (aGVHD) was observed in 13 patients (median,+27; range, 16–97). The cumulative incidence (CI) of aGVHD grade 2–4 and grade 3–4 at 100 days was 46% and 10%, respectively. Six patients developed a noninfectious fever (median,+18.5; range, 6–53) and 5 of them were diagnosed with macrophage activation syndrome (MAS). The CI of MAS at 100 days was 22%. Cytokine Release Syndrome (CRS) was observed in 13 patients (median,+6; range, 3–13). One patient experienced Posterior Reversible Encephalopathy Syndrome at day +53. In univariate analysis, neither the number of nivolumab cycles nor the time from last nivolumab dose to allo-SCT have an impact on early noninfectious toxicities.
About infective complications, four bacterial (median,+10; range, 6–83) and 20 viral infections (median,+37; range, 13–83) were reported. In particular, 7 patients experienced CMV reactivation and 2 CMV disease. The CI of CMV reactivation was 23% at 100 days.
With a median follow-up of 504 days (range, 81–1195), only 1 patient relapsed at day +116.
Three deaths were attributed to toxicity (median,+125; range, 76–419). The specific causes of death were: aGVHD 1, CMV pneumonia 1 and PTLD 1. The CI of non-relapse mortality at 100 days and 1 year was 4% and 13%, respectively.
The 2-years progression-free survival and overall survival were 72% and 72%, respectively. The CI of relapse was 4% at 2 years.
In conclusion, our study suggests that allo-SCT in HL patients treated with PD-1 inhibitors is feasible. The incidence of aGVHD grade 2–4 did not appear different from what reported, while the incidence of aGVHD grade 3–4 is lower compared to previous study (Merryman, Blood 2017), probably due to different donor types in the two cohorts (more haplo-SCT in our cohort). As previously reported, we observed a noninfectious fever in a minority of patients. Most of them were diagnosed as MAS and were successfully treated with short courses of steroids. CRS was observed only after haplo- SCT. The incidence of CMV reactivation was low.