Post-transplantation cyclophosphamide reduces the incidence of acute graft-versus-host disease in patients with acute myeloid leukemia/myelodysplastic syndromes who receive immune checkpoint inhibitors after allogeneic hematopoietic stem cell transplantation

Abstract

BackgroundImmune checkpoint inhibitors (ICIs) are being used after allogeneic hematopoietic stem cell transplantation (alloHCT) to reverse immune dysfunction. However, a major concern for the use of ICIs after alloHCT is the increased risk of graft-versus-host disease (GVHD). We analyzed the association between GVHD prophylaxis and frequency of GVHD in patients who had received ICI therapy after alloHCT.MethodsA retrospective study was performed in 21 patients with acute myeloid leukemia (n=16) or myelodysplastic syndromes (n=5) who were treated with antiprogrammed cell death protein 1 (16 patients) or anticytotoxic T lymphocyte-associated antigen 4 (5 patients) therapy for disease relapse after alloHCT. Associations between the type of GVHD prophylaxis and incidence of GVHD were analyzed.ResultsFour patients (19%) developed acute GVHD. The incidence of acute GVHD was associated only with the type of post-transplantation GVHD prophylaxis; none of the other variables included (stem cell source, donor type, age at alloHCT, conditioning regimen and prior history of GVHD) were associated with the frequency of acute GVHD. Twelve patients received post-transplantation cyclophosphamide (PTCy) for GVHD prophylaxis. Patients who received PTCy had a significantly shorter median time to initiation of ICI therapy after alloHCT compared with patients who did not receive PTCy (median 5.1 months compared with 26.6 months). Despite early ICI therapy initiation, patients who received PTCy had a lower observed cumulative incidence of grades 2–4 acute GVHD compared with patients who did not receive PTCy (16% compared with 22%; p=0.7). After controlling for comorbidities and time from alloHCT to ICI therapy initiation, the analysis showed that PTCy was associated with a 90% reduced risk of acute GVHD (HR 0.1, 95% CI 0.02 to 0.6, p=0.01).ConclusionsICI therapy for relapsed acute myeloid leukemia/myelodysplastic syndromes after alloHCT may be a safe and feasible option. PTCy appears to decrease the incidence of acute GVHD in this cohort of patients.

Hematologic complications of immune checkpoint inhibitors

“… 46,47 In 1 institution, cyclophosphamide after SCT permitted the initiation of ICI therapy much earlier in the course of the relapse. 52 …”

Case Report: Preemptive Treatment With Low-Dose PD-1 Blockade and Azacitidine for Molecular Relapsed Acute Myeloid Leukemia With RUNX1-RUNX1T1 After Allogeneic Hematopoietic Stem Cell Transplantation

“…Therefore, we suggest that early initiation of ICIs therapy after allo-HSCT is feasible and deserves attention. Besides, a recent study has also showed that irAEs directly attributed to ICIs therapy may be alleviated in patients with AML/myelodysplastic syndrome (MDS) who receive post-transplantation cyclophosphamide as GVHD prophylaxis ( 45 ). Currently, we have not changed our conditioning regimen in advance considering the possibility of disease relapse and ICIs therapy.…”

Checkpoint Inhibitors and Other Immune-Based Therapies in Acute Myeloid Leukemia

“…33 In the posttransplant setting, another analysis of 21 patients with AML and MDS treated with ICIs following allo-SCT relapse demonstrated that the use of PTCy prophylaxis was associated with a 90% reduced risk of acute GVHD. 34 CD47/SIRPΑ BLOCKADE CD47 is a widely expressed transmembrane protein that interacts with the signal regulatory protein α (SIRPα) expressed on the surface of macrophages and dendritic cells. 35 This interaction between CD47 and SIRPα leads to downstream signaling and inhibition of phagocytosis.…”