title: Lower malignancy rates in renal allograft recipients converted to sirolimus-based, calcineurin inhibitor-free immunotherapy: 24-month results from the CONVERT trial.
abstract: BACKGROUND
  Long-term immunosuppression imposes increased malignancy risk in renal allograft recipients, significantly contributing to overall morbidity and mortality. This study examined malignancy rates in renal allograft recipients at 2 years after conversion to a sirolimus (SRL)-based, calcineurin inhibitor (CNI)-free regimen.
  
  
  METHODS
  This open-label, randomized, multicenter study (the CONVERT Trial) randomly assigned 830 patients to SRL conversion (n=555) or CNI continuation (n=275). Patients with history of posttransplant lymphoproliferative disease or known/suspected malignancy within 5 years before screening were excluded. As part of standard safety measurements, subjects were monitored for any malignancy occurrence; both skin and nonskin malignancies were reported, even if the patient discontinued from the therapy. Malignancy rates were analyzed based on exposure time to study drugs (i.e., number of events per 100 person-years of follow-up).
  
  
  RESULTS
  At 2 years postconversion, the total number of malignancies per 100 person-years of exposure was significantly lower among SRL conversion patients compared with CNI continuation (2.1 vs. 6.0, P<0.001). Patients undergoing SRL-based, CNI-free therapy had significantly lower rates of the subset of nonmelanoma skin carcinomas through 2 years postconversion (1.2 vs. 4.3, P<0.001). This difference persisted after excluding patients with a history of malignancy before randomization. The rate of all other malignancies was not significantly different between treatment groups (P=0.058).
  
  
  CONCLUSIONS
  In renal allograft recipients, SRL-based immunosuppression was associated with a lower rate of malignancy at 2 years postconversion compared with continuation of CNI-based immunosuppression. This reduction was driven by a significant reduction in nonmelanoma skin carcinoma rates; the rate of all other malignancies was numerically lower but did not achieve statistical significance.
authors.affiliation: Departamento de Trasplantes, Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, DF, Mexico. josefinaalberu@hotmail.com
authors.forename: Josefina
authors.initials: J
authors.lastname: Alberú
authors.forename: Michael D
authors.initials: MD
authors.lastname: Pascoe
authors.forename: Josep M
authors.initials: JM
authors.lastname: Campistol
authors.forename: Francesco P
authors.initials: FP
authors.lastname: Schena
authors.forename: Maria Del Carmen
authors.initials: Mdel C
authors.lastname: Rial
authors.forename: Martin
authors.initials: M
authors.lastname: Polinsky
authors.forename: John F
authors.initials: JF
authors.lastname: Neylan
authors.forename: Joan
authors.initials: J
authors.lastname: Korth-Bradley
authors.forename: Robert
authors.initials: R
authors.lastname: Goldberg-Alberts
authors.forename: Eric S
authors.initials: ES
authors.lastname: Maller
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D000075202:Contraindications; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000401:mortality* / Q000517:prevention & control; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491861:CABIN1 protein, human; D007166:Immunosuppressive Agents; D020123:Sirolimus