Patients with hematologic malignancies who receive allogeneic hematopoietic cell transplant (HCT) are at risk for developing acute graft-versus-host disease (GVHD) — a condition where a patient’s body attacks and rejects donor cells.
However, researchers have recently found that treatment with a multidose regimen of the novel human CD24 fusion protein CD24Fc/MK-7110 combined with the drugs tacrolimus and methotrexate in a phase 2a study “produced sustained drug exposure with similar safety outcomes when compared with single-dose regimens,” according to findings published in the journal Blood.
The authors of the study explained that the combined treatments “selectively target and mitigate inflammation due to damage-associated molecular patterns underlying acute GVHD while preserving protective immunity after myeloablative conditioning.”
“These important results stand as the first proof of concept that targeting DAMP (damage-associated molecular pattern) signaling could dampen acute GVHD in humans,” noted Dr. Paul J. Martin, professor emeritus in the clinical research division of the Fred Hutchinson Cancer Center and in the division of hematology and oncology at the University of Washington in a Blood commentary article published alongside the study findings.
Patients who receive healthy, blood-forming cells from a donor via human leukocyte antigen–matched unrelated donor (MUD) allogeneic hematopoietic stem cell transplantation (HSCT) can often develop GVHD, as the researchers explained. Martin noted that such patients are typically treated with agents that target T cells, part of the body’s immune system, but with their current findings researchers have shown that “agents targeting antigen-presenting cells can also help prevent GVHD,” he wrote.
The trial included a placebo-controlled dose-finding and treatment duration phase evaluating groups of six patients, which was then followed by a dose-expansion phase with 20 additional patients treated with a regimen based on the findings of the dose-escalation phase.
The 26 patients treated with the combination in the CD24Fc expansion cohort experienced a 180-day grade 3 to 4 (severe to serious) acute GVHD-free survival rate of 96.2%, compared with 73.6% in the 92-patient control group, researchers stated.
The study authors further noted that “no participants in the CD24Fc escalation or expansion phases experienced dose-limiting toxicities (DLTs). The multidose regimen of CD24Fc was well-tolerated with no DLTs and was associated with high rates of severe acute GVHD-free survival after myeloablative MUD HSCT.”
Martin also noted that upon further analysis, there was no evidence of a statically or clinically significant difference in either overall survival (time a patient lives after treatment, regardless of disease status) or the risk of chronic GVHD or relapse between the two groups of patients.
“Results of the current study signal the merit of further development to evaluate the extent to which ancillary targeting of DAMP signaling with CD24Fc could be used together with conventional immunosuppression to prevent acute GVHD without increasing the risks of recurrent or progressive malignancy or infection, especially in patients treated with high-intensity regimens of chemotherapy and radiation before HCT,” Martin wrote.
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