Use of Leflunomide in Renal Transplant Recipients with Ganciclovir-Resistant/Refractory Cytomegalovirus Infection: A Case Series from the University of Chicago

Abstract

Introduction: Although antiviral prophylaxis for cytomegalovirus (CMV) is widely used, CMV infection remains common in renal transplant recipients with adverse consequences. Methods: We report 5 cases of renal transplant recipients with resistant CMV infection who were successfully managed with leflunomide at the University of Chicago Medical Center. Results: Five renal transplant recipients (2 simultaneous pancreas/kidney transplants, 3 deceased donor kidney transplants) were diagnosed with GCV-resistant CMV infection from 2003 to 2011. Of the 4 patients who had resistance genotype testing, 3 showed a UL97 mutation and 1 patient had a clinically resistant CMV infection. All patients received CMV prophylaxis with valganciclovir for 3 months. The number of days from the date of transplant to viremia ranged from 38 to 458 days (median 219). All 5 patients received other antiviral agents (e.g. ganciclovir, foscarnet), and in 4 patients, viremia was cleared before leflunomide was initiated as consolidation (or maintenance) therapy. Conclusion: Leflunomide was well tolerated and successful in preventing recurrence of viremia in renal transplant recipients with resistant CMV infection. The beneficial effect of leflunomide in this setting warrants further investigation.

The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation

“…[318][319][320] Leflunomide has been advocated in case reports and small series. [321][322][323][324] Evidence for efficacy is limited and caution is advised when used for cases of severe disease or with high viral loads. Monitoring for drug metabolite levels and liver toxicity is recommended.…”

Ganciclovir‐Resistant Cytomegalovirus Infection in Abdominal Solid Organ Transplant Recipients: Case Series and Review of the Literature

“…LEF has been shown to have a role as a secondary prophylactic or maintenance agent. In a case series of five patients, LEF successfully lowered VL in all five patients with concomitant antivirals, and four of five patients continued LEF therapy after attaining negativity . In addition, LEF may have a role in the treatment of recurrence, as was suggested in a recently published case report describing the use of LEF monotherapy for low‐level VL recurrence in the outpatient setting .…”

“…In a case series of five patients, LEF successfully lowered VL in all five patients with concomitant antivirals, and four of five patients continued LEF therapy after attaining negativity. 36 In addition, LEF may have a role in the treatment of recurrence, as was suggested in a recently published case report describing the use of LEF monotherapy for low-level VL recurrence in the outpatient setting. 37 A 2016 review of the literature on LEF treatment of patients with GR-CMV demonstrated a success rate of seven of eight patients (88%) in cases with a peak VL < 10 5 , whereas only 10 of 18 patients (56%) of those with peak VLs > 10 5 had long-term responses to LEF therapy.…”

Experience with leflunomide as treatment and as secondary prophylaxis for cytomegalovirus infection in lung transplant recipients: A case series and review of the literature

“…Due to its unique antiviral activity—interfering with virion assembly and not with viral DNA synthesis—cross‐resistance with other anti‐CMV drugs is not expected, and a synergistic effect with GCV or FOS should be seen . Some authors now advocate the combination of leflunomide with GCV or FOS as induction therapy followed by long‐term maintenance monotherapy . This approach would allow faster clearing of the viremia, shorter course of GCV or FOS (reducing the incidence of side effects induced by these drugs), and lower risk of induction resistance to antiviral drugs.…”