Key result
Sirolimus conversion is linked to ~66% lower de novo malignancy risk vs CNI post-heart transplant.
Why the study?
Malignancy is a major cause of late post-heart transplantation mortality, and the decreased mortality risk with long-term sirolimus primary immunosuppression is not fully explained by attenuation of cardiac allograft vasculopathy progression.
Does conversion from calcineurin inhibitor-based to sirolimus-based maintenance immunosuppression reduce the incidence of de novo malignancies in heart transplant recipients?
Cohort (n=523)
No
Does conversion from calcineurin inhibitor-based to sirolimus-based maintenance immunosuppression reduce the incidence of de novo malignancies in heart transplant recipients?
Conversion from calcineurin inhibitors to sirolimus-based immunosuppression after heart transplantation significantly lowers the long-term risk of de novo malignancies, PTLD, and recurrent non-melanoma skin cancers, helping explain the late survival benefit of sirolimus.
Answers are grounded in this paper and cite their sources.
Sirolimus may be considered in malignancy-prone heart transplant recipients; leaves open prospective confirmation of survival benefit.
BACKGROUND Malignancy is a major cause of late post-heart transplantation (HT) mortality. Sirolimus (SRL) exerts antiproliferative properties and its long-term use in HT as primary immunosuppression (IS) is associated with decreased mortality risk that is not fully explained by attenuation of cardiac allograft vasculopathy progression. OBJECTIVES This study sought to examine whether conversion from calcineurin inhibitor (CNI)-based to SRL-based IS was associated with decreased risk of malignancy post-HT. METHODS Overall, 523 patients underwent HT between 1994 and 2016 at a single institution. The main outcomes included incidence of overall de novo malignancies (excluding non-melanoma skin cancers [NMSCs]), post-transplantation lymphoproliferative disorders (PTLD), and first and subsequent primary occurrences of NMSC post-HT. RESULTS The study identified 307 patients on SRL-based and 216 on CNI-based maintenance IS. Over a median follow-up of 10 years after HT, overall de novo malignancies (non-NMSC) occurred in 31% of CNI patients and in 13% of SRL patients (adjusted hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.18 to 0.62; p < 0.001). The incidence of the first NMSC was similar in the SRL and CNI groups (HR: 0.92; 95% CI: 0.66 to 1.28; p = 0.62). However, conversion to SRL was significantly associated with a decreased risk of subsequent primary occurrences of NMSC compared with that of CNI (adjusted HR: 0.44; 95% CI: 0.28 to 0.69; p < 0.001). The adjusted PTLD risk was significantly decreased in the SRL group (HR: 0.13; 95% CI: 0.03 to 0.59; p = 0.009). Late survival post-HT was markedly decreased in patients who developed non-NMSC, PTLD, or non-PTLD compared with patients who did not develop these malignancies, whereas NMSC had no significant effect on survival. CONCLUSIONS Conversion to SRL was associated with a decreased risk of all de novo malignancies, PTLD, and subsequent primary occurrences of NMSC after HT. These findings provided further explanation of the late survival benefit with long-term SRL use.
No takes yet. Share an insight, caveat, or question.
Asleh et al. (2019) conducted a cohort in Heart transplantation (n=523). Sirolimus-based maintenance immunosuppression vs. Calcineurin inhibitor-based maintenance immunosuppression was evaluated on Overall de novo malignancies (excluding non-melanoma skin cancers [NMSCs]) (adjusted HR 0.34, 95% CI 0.18-0.62, p=<0.001). Conversion to sirolimus-based immunosuppression reduced overall de novo non-NMSC malignancies vs CNI post-heart transplant (13% vs 31%; adjusted HR 0.34; 95% CI 0.18-0.62; p<0.001).
Synapse has enriched 10 related papers. Consider them for comparative context: