cmx-001 and Viremia

Human herpesvirus 6B (HHV-6B) frequently reactivates after allogeneic hematopoietic cell transplantation (HCT). There are no randomized studies of antiviral treatments to prevent HHV-6B reactivation. Brincidofovir has high in vitro activity against HHV-6B and other DNA viruses, but its in vivo activity for HHV-6B has not been demonstrated. We performed a post hoc analysis of a randomized controlled trial of twice-weekly oral brincidofovir for cytomegalovirus prophylaxis after allogeneic HCT to study the effect of brincidofovir on HHV-6B reactivation. We included patients randomized within 2 weeks of HCT and who received at least 6 consecutive doses of study drug after randomization. We tested plasma for HHV-6B through week 6 post-HCT. The cohort consisted of 92 patients receiving brincidofovir and 61 receiving placebo. The cumulative incidence of HHV-6B plasma detection through day 42 post-HCT was significantly lower among patients receiving brincidofovir (14.2%) compared with placebo (32.4%; log-rank, 0.019). In an adjusted Cox model, brincidofovir exposure remained associated with a lower hazard for HHV-6B plasma detection (hazard ratio, 0.40; 95% confidence interval, 0.20-0.80). In conclusion, brincidofovir prophylaxis reduced HHV-6B reactivation after allogeneic HCT in a post hoc analysis of a randomized controlled trial. These data support the study of intravenous brincidofovir for HHV-6B prophylaxis.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antiviral Agents; Cohort Studies; Cytosine; DNA, Viral; Female; Follow-Up Studies; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Herpesvirus 6, Human; Humans; Incidence; Male; Middle Aged; Organophosphonates; Prognosis; Randomized Controlled Trials as Topic; Roseolovirus Infections; United States; Viral Load; Viremia; Virus Activation; Young Adult

Topics: Antiviral Agents; Cytosine; Hematopoietic Stem Cell Transplantation; Herpesvirus 6, Human; Humans; Incidence; Organophosphonates; Roseolovirus Infections; Viremia

Adenovirus infection is a well-known complication in patients receiving hematopoietic stem cell transplantation (HSCT). Brincidofovir (BCV) is an orally bioavailable lipid conjugate of cidofovir, which has activity against adenoviruses. We present a review of adenovirus infections treated with BCV which were unresponsive to cidofovir initially in 4 patients and it was used upfront in one patient. Children with adenovirus infection following HSCT treated with BCV, between July 2014 and February 2018 were recognized. Five patients including 3 male and 2 female with a median age of 10 years (range, 2.2 to 10 y) were identified. The median days of adenoviremia detection was 18 days (range, 7 to 303 d) posttransplant. The median peak viral load by quantitative polymerase chain reaction was 21,38,000 copies/mL (range, 1,77,200 to 31,97,000 copies/mL). The median time from first detection of adenoviremia to become negative was 30 days (range, 15 to 113 d). The sites involved were gastrointestinal tract in all patients and 2 patients had additional respiratory tract involvement. Two patients survived and 3 patients died of sepsis. All patients responded well to BCV and no adverse effect was noticed. We saw the good safety profile and excellent antiadenoviral activity of BCV in pediatric patients receiving HSCT without the nephrotoxicity and it may have a role in preemptive therapy.

Topics: Adenovirus Infections, Human; Adolescent; Antiviral Agents; Child; Child, Preschool; Cytosine; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Male; Organophosphonates; Salvage Therapy; Viremia

Brincidofovir (CMX001) is an oral agent with activity against double-strand DNA viruses undergoing clinical trials in immunocompromised patients. We report a patient clinically diagnosed with brincidofovir-related gastrointestinal (GI) toxicity and his histologic findings. A 2-year-old boy with medulloblastoma undergoing autologous hematopoietic cell transplantation developed adenovirus viremia 9 days posttransplant. After initial treatment with intravenous cidofovir he was started on oral brincidofovir as part of a clinical trial. He developed hematochezia, anorexia, and emesis 11 weeks later. Sigmoid colon biopsy showed marked crypt drop out, moderate epithelial apoptosis, and lamina propria edema. The pathologic diagnosis was drug-related injury versus infection. Brincidofovir toxicity was diagnosed clinically and the drug was discontinued. His GI symptoms improved in 2 weeks with supportive care and octreotide. Brincidofovir causes GI toxicity and histologically demonstrates epithelial apoptosis and crypt injury, similar to graft versus host disease and mycophenolate mofetil toxicity.

Topics: Adenoviridae; Adenoviridae Infections; Autografts; Child, Preschool; Colon; Cytosine; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Medulloblastoma; Octreotide; Organophosphonates; Viremia

Polyomavirus-associated nephropathy (PVAN) is common in patients who have undergone kidney transplantation and has been reported in hematopoietic stem cell (HSC) transplant recipients. Aside from reduction of immunosuppression, few therapeutic options exist for treatment of PVAN. We report a case of PVAN in a severely immunocompromised allogeneic HSC transplant recipient that was treated with brincidofovir without reduction of immunosuppression. We review our institutional experience of PVAN in HSC transplantation and discuss the potential use of brincidofovir for treatment.

Topics: BK Virus; Cytomegalovirus Infections; Cytosine; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Kidney Diseases; Male; Middle Aged; Organophosphonates; Polyomavirus; Polyomavirus Infections; Tumor Virus Infections; Viremia