Interleukin-22 Dimer F-652 Plus Systemic Corticosteroids Demonstrated High Response Rate Among Patients With Acute GVHD

Results from a Phase 2 Trial

According to findings from a phase 2 trial recently published in Blood, the novel recombinant human interleukin-22 dimer, F-652, plus systemic corticosteroids was an effective treatment among patients with newly diagnosed lower gastrointestinal acute graft-versus-host disease (GVHD), yielding high response rates. 

Doris M. Ponce, MD, Memorial Sloan Kettering Cancer Center, New York, New York, and coauthors stated, “GVHD is a major cause of morbidity and mortality following allogeneic hematopoietic transplantation.” 

To expand current research on therapeutic approaches for this condition, the study authors looked to assess interleukin-22, which had previously shown efficacy in promoting “epithelial regeneration and induc[ing] innate antimicrobial molecules.”

In this study, Dr Ponce et al aimed to evaluate the efficacy and safety of a novel recumbent human interleukin-22 dimer, F-652, when used in combination with systemic corticosteroids for the treatment of lower gastrointestinal acute GVHD. The primary endpoint was treatment response rate, measured at 28 days. 

27 patients with newly diagnosed patients with lower gastrointestinal acute GVHD were enrolled in this study and received F-652 plus systemic corticosteroids. Adverse events were closely monitored, and fecal samples were collected to assess the correlation between treatment response and changes in fecal microbiota composition. 

Results indicated that 70% of patients (n = 19) achieved a day-28 treatment response. The most common adverse events were cytopenias and electrolyte abnormalities. However, no dose-limiting toxicities were reported. Patients demonstrated a distinct fecal microbiota composition characterized by the expansion of commensal anaerobes. This shift came with an overall increase in microbial α-diversity, which suggests an improvement in GVHD-associated dysbiosis. 

As the primary endpoint was met, the study authors concluded that these results demonstrate “a potential approach for combining immunosuppression with tissue-supportive strategies to enhance recovery of damaged mucosa and promote microbial health in patients with gastrointestinal GVHD.”

Source: 

Ponce DM, Alousi AM, Nakamura R, et al. A phase 2 study of interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract. Blood. 2022;141(12):1389-1401. doi: 10.1182/blood.2021015111