- March 22, 2020
- Posted by: PharmaScroll
A study, published in Cancers, indicated that hematopoietic stem cell transplantation (HSCT) with prior use of checkpoint inhibitors appears feasible in patients with acute myeloid leukemia (AML) and/or myelodysplastic syndromes (MDS) and the use of post-HSCT cyclophosphamide (PTCy) as graft-versus host disease (GVHD) prophylaxis improves outcomes.
Taken together, these data suggests that the use of prior checkpoint inhibitors needs to be considered within the donor/hematopoietic stem cell selection and GVHD prophylaxis plan for patients undergoing HSCT.
In this study, a retrospective analysis of 43 patients with AML and/or MDS who were treated with an antiprogrammed cell death protein 1 (PD-1) (32 patients) or anticytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (9 patients) blockade or both (2 patients) prior to HSCT with the primary outcome of acute GVHD by day 100 after HSCT was conducted. Outcome analyses were stratified by GVHD prophylaxis as use of post-HSCT cyclophosphamide (PTCy) (22 patients) or not (non-PTCy) (21 patients).
The PTCy cohort showed a trend toward lower grade 3 to 4 acute GVHD when compared with the non-PTCy cohort (5% vs 22%), though the rates of grade 2 to 4 acute GVHD were similar (49% vs 56%). Additionally, the interval between checkpoint inhibitors and HSCT did not appear to impact the incidence of acute GVHD. However, a higher incidence of grade 3 to 4 acute GVHD was observed in patients who received >4 treatments of checkpoint inhibitors prior to HSCT if they were not administered PTCy as GVHD prophylaxis (43% vs 12%).
Moreover, matched control analyses using subjects with no prior use of checkpoint inhibitors confirmed the increase in grade 3 to 4 acute GVHD with those agents. However, that increased risk was limited to those who did not receive PTCy and was not observed in patients who received PTCy as GVHD prophylaxis. Furthermore, despite improvement in GVHD with the use of PTCy, disease control was not compromised and progression-free survival at 1 year was found to be superior for patients who were treated with PTCy compared with those not receiving PTCy among patients with prior use of checkpoint inhibitors (55% vs 22%).
Notably, the lack of correlative studies investigating potential mechanisms by which PTCy mitigates the risk of acute GVHD in patients exposed to checkpoint inhibitors prior to HSCT is a limitation of the study.
Many questions remain regarding the safest and most efficacious approach for incorporating checkpoint inhibitors into the treatment of patients with hematologic malignancies, especially AML and/or MDS, who are candidates for allogeneic HSCT. Several ongoing, prospective, phase II/III trials will likely help to provide more answers.
Several ongoing studies using different checkpoint inhibitors across patients with various hematologic malignancies (lymphoma, AML, and MDS) in the frontline or salvage settings before allergenic HSCT, the researchers suggested that a joint effort is necessary to collect the transplantation data prospectively, including immunologic correlates, not only in the peripheral blood but also in the tissue compartments.
“Only by using such an approach the company will be able to optimize the treatment schema in the peri-transplantation setting with improved outcomes,” the authors wrote.
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Article Source: https://www.cancernetwork.com/article/use-post-hsct-cyclophosphamide-improves-transplantation-outcomes-amlmds
Image Source: https://www.hematologyadvisor.com/wp-content/uploads/sites/14/2019/01/stemcelltherapyg615614140_1469406.jpg