Background: Immunotherapy with checkpoint inhibitors (anti-PD-1) is highly effective in relapsed/refractory (R/R) classical Hodgkin Lymphoma (cHL) and leads to more than 70% overall response rate. However, long-term progression-free survival rate is not sufficient. Consolidation with ASCT after anti-PD-1 could be a very promising option even among previously chemorefractory patients. Nevertheless, there is not enough experience about the safety and feasibility of ASCT after anti-PD-1 in the context of possible immune-related adverse events (AE). Aims: to assess the safety and feasibility of ASCT after anti-PD-1 therapy in patients with R/R cHL. Methods: We retrospectively analysed patients with cHL who previously underwent ASCT from November 2018 until December 2021 after treatment with anti-PD-1. A median patient age was 34 years (range, 20-55), 22 patients were female, 21 - male. Patients received anti-PD-1 as monotherapy (n=17), combination of anti-PD-1 and chemotherapy (n=4), anti-PD-1 monotherapy followed by combination of anti-PD-1 and chemotherapy (n=14), anti-PD-1 monotherapy followed by salvage therapy (n=3) and other (n=2). A median number of anti-PD-1 cycles was 6 (range, 1-45). The median time from the last dose of anti-PD1 was 69 days (range, 14-365). Conditioning regimen for ASCT consisted of BeEAM (n=12), BeAC (n=30) and other (n=1). Safety assessment was performed by Common Terminology Criteria for Adverse Events (CTCAE) (v5.0). Results: Forty-three eligible patients were enrolled in this analysis. A median time to engraftment was 10.5 days (range, 9-26). A median time to platelet count > 20x109/L was 13.5 days (range, 7-43). A median use of G-CSF after high-dose chemotherapy followed by ASCT was 9 days (range, 0-26). PEG-G-CSF (empegfilgrastim 7.5 mg/ml once) was used in 10 patients (23.3%). Plerixafor was used in 6 patients (14%). Neutropenic fever was observed in 32 patients (74.4%). Documented infections were reported in 19 patients (44.2%) among which were 5 cases of clostridial colitis (11.6%). A median intravenous administration of antibiotics was 8 days (range, 0-23). Grade 3-4 mucositis and enteropathy was reported in 2 patients (4.6%) and 6 (14%), respectively. Other non-hematological toxicity was observed in 10 patients (23.4%): 8 patients (18.6%) developed engraftment syndrome (that was successfully treated with steroids), grade 4 autoimmune toxic myocarditis was reported in 1 patient (2.3%). One death due to grade 5 autoimmune myocarditis in combination with grade 5 autoimmune pneumonitis was reported (2.3%). A median duration of hospitalization was 25 days (range, 14-72). Transplant-related mortality (TRM) was reported in 2 patients (4.6%). Image:Summary/Conclusion: The obtained data on safety of ASCT after anti-PD-1 treatment generally correspond to the data of international studies. Toxicity profile tends to be very similar to the published data about ASCT without anti-PD-1 previous treatment, especially in terms of TRM. However, we observe a high incidence of engraftment syndrome that can lead to fulminant immune-related AE (myocarditis and pneumonitis) probably. Attention should be paid to the defining of optimal “wash-out” period after last dose of anti-PD-1 and early defining of possible life-threatening immune related AE (especially myocarditis and pneumonitis).
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Mochkin et al. (2022) studied this question.