Bezlotoxumab As Treatment for Recurrent/Chronic Clostridioides Difficile Infection in Stem Cell Transplant Recipients

Introduction

Clostridioides difficile infection (CDI) represents a significant health risk to pediatric stem cell transplant (SCT) patients, leading to increased comorbidity and mortality. Due to prolonged immunosuppression in the post-transplant period, CDI is frequently complicated by recurrent disease, requiring repeated, prolonged antibiotic usage and increased rates of hospitalization. Therefore, there is a need for other adjunct therapies to treat recurrent CDI (rCDI) in the pediatric population. Bezlotoxumab is a human monoclonal antibody that has demonstrated efficacy in pediatric patients based on the recent MODIFY III trial results. However, the safety and efficacy of bezlotuxumab has not been studied in pediatric patients undergoing a SCT, and no data exists to detail its impact on common immunosuppressants such as tacrolimus and mycophenolate mofetil (MMF). We describe here two cases where bezlotoxumab was used in conjunction with conventional antibiotic therapy to treat rCDI in pediatric SCT patients without disease recurrence as indicated by absence of symptoms.

Methods

This was a retrospective chart review of pediatric patients with rCDI who received a SCT at MD Anderson Cancer Center.

Results

Case 1

A 6-year-old female was diagnosed at 2 years old with MLL/KMT2A acute myeloid leukemia (AML). The patient first developed C. difficile colitis prior to her first transplant, which was confirmed via DNA and toxin EIA testing. The patient required a prolonged oral vancomycin taper with improvement of her symptoms. Following relapse of AML, the patient enrolled on a clinical trial to receive a KMT2A inhibitor, revumenib, achieved remission, and eventually proceeded to a second SCT using a single cord donor. The patient's post-SCT course was complicated by Streptococcus mitis/oralisbacteremia, resulting in a long course of broad-spectrum antibiotics with vancomycin and meropenem. Following discharge from her second SCT, the patient was diagnosed with another episode of CDI 2 months post-SCT, with positivity of C. difficile DNA and toxin EIA. She was treated with bezlotoxumab (10 mg/kg) and a fidaxomicin taper. Since, she has not reported any symptoms of CDI recurrence and remains in disease remission >800 days after SCT with no GVHD or complications of her SCT.

Case 2

An 8-year-old female was diagnosed at 5 years old with DEK/NUP214 and FLT3-ITD positive AML. Her chemotherapy treatment course was complicated by several infections including Granulicatella adiacens and Streptococcus viridans bacteremia, Aspergillus teres pneumonia, and rCDI that progressed to neutropenic enterocolitis. She required several systemic antimicrobials for treatment of her infections, as well as a month-long taper of oral vancomycin to treat rCDI. The patient underwent SCT using a matched unrelated donor. Six months after her transplant, she developed loose stools and tested positive for stool C. diff toxin and antigen. Oral vancomycin treatment was initiated, and she was treated for 21 days. She tested negative for C. diff on repeat stool testing with negative toxin EIA and DNA but then developed CDI 6 months later. At this recurrence, she was hospitalized for dehydration and treated with oral vancomycin, subsequently transitioning to oral fidaxomicin over a 21-day taper. She received IV bezlotoxumab (10 mg/kg) with the goal of preventing future recurrences. The patient remains in remission >800 days following SCT without GVHD and has not had any reported CDI recurrence or symptoms of diarrhea.

Conclusion

We present 2 cases of pediatric patients who received a single dose of bezlotoxumab in the peri-transplant period for rCDI. In each case, the patient tolerated treatment without any reported adverse effects and remain in disease remission at time of publication. There appeared to be no adverse interactions between bezlotoxumab and drugs in the post-transplantation period, including with immunosuppressants such as tacrolimus and MMF. All patients were confirmed to have no gastrointestinal GVHD causing the diarrhea, and no recurrence of diarrhea occurred after bezlotoxumab. This case series strongly suggests the potential utility of bezlotoxumab for treating rCDI in the pediatric SCT patient population.

No relevant conflicts of interest to declare.