Safety and Efficacy of Fecal Microbiota, Live-jslm, in Preventing Recurrent Clostridioides difficile Infection in Participants Who Were Mildly to Moderately Immunocompromised in the Phase 3 PUNCH CD3-OLS Study

Background. Fecal microbiota, live-jslm (RBL; Rebyota), is the first Food and Drug Administration–approved, single-dose, microbiota–based live biotherapeutic to prevent recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care antimicrobials. Patients who are immunocompromised are often considered at higher risk for C difficile infection, including recurrence, as compared with those who are immunocompetent. This subgroup analysis of PUNCH CD3-OLS (NCT03931941) evaluated RBL safety and efficacy in participants with rCDI who were considered mildly to moderately immunocompromised. Methods. Participants with rCDI who had immunocompromising conditions and/or were taking immunosuppressive medications were included. Treatment-emergent adverse events (TEAEs) were collected for up to 6 months following RBL administration. Efficacy outcomes included treatment success at 8 weeks and sustained clinical response at 6 months. Results. Overall, 793 participants were enrolled in PUNCH CD3-OLS and 697 received RBL; 141 were included in the immunocompromised subgroup. TEAEs within 8 weeks were reported by 44.7% and 48.0% of participants in the immunocompromised and nonimmunocompromised subgroups, respectively; most events were mild or moderate gastrointestinal disorders. Serious TEAEs within 8 weeks were reported by 4.3% and 3.8% of participants in the immunocompromised and nonimmunocompromised subgroups. No RBL-related systemic infections occurred. In the immunocompromised subgroup, the treatment success rate at 8 weeks was 75.7% and the sustained clinical response rate at 6 months was 88.7%; similar rates were observed in the nonimmunocompromised subgroup (73.3% and 91.6%). Conclusions. Results of this subgroup analysis of PUNCH CD3-OLS suggest that RBL is safe and efficacious for the prevention of rCDI in participants with mildly to moderately immunocompromising conditions.