Incidence of Malignancies in Patients Treated With Sirolimus Following Heart Transplantation

Rabea Asleh, Alfredo L. Clavell, Naveen Luke Pereira, Byron Smith, Alexandros Briasoulis, Hilmi Alnsasra, Walter K Kremers, Thomas Matthew Habermann, Clark C. Otley, Xin Li, Brooks Sayre Edwards, John M. Stulak, Richard C. Daly, Sudhir S. Kushwaha

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2676-2688
Number of pages13
JournalJournal of the American College of Cardiology
Volume73
Issue number21
DOIs
StatePublished - Jun 4 2019

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Sirolimus
Heart Transplantation
Skin Neoplasms
Lymphoproliferative Disorders
Incidence
Transplantation
Neoplasms
Confidence Intervals
Immunosuppression
Survival
Mortality
Allografts
Maintenance
Calcineurin Inhibitors

Keywords

  • heart transplantation
  • immunosuppression
  • malignancy
  • sirolimus

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Incidence of Malignancies in Patients Treated With Sirolimus Following Heart Transplantation. / Asleh, Rabea; Clavell, Alfredo L.; Pereira, Naveen Luke; Smith, Byron; Briasoulis, Alexandros; Alnsasra, Hilmi; Kremers, Walter K; Habermann, Thomas Matthew; Otley, Clark C.; Li, Xin; Edwards, Brooks Sayre; Stulak, John M.; Daly, Richard C.; Kushwaha, Sudhir S.

In: Journal of the American College of Cardiology, Vol. 73, No. 21, 04.06.2019, p. 2676-2688.

Research output: Contribution to journalArticle

Asleh, R, Clavell, AL, Pereira, NL, Smith, B, Briasoulis, A, Alnsasra, H, Kremers, WK, Habermann, TM, Otley, CC, Li, X, Edwards, BS, Stulak, JM, Daly, RC & Kushwaha, SS 2019, 'Incidence of Malignancies in Patients Treated With Sirolimus Following Heart Transplantation', Journal of the American College of Cardiology, vol. 73, no. 21, pp. 2676-2688. https://doi.org/10.1016/j.jacc.2019.03.499
Asleh, Rabea ; Clavell, Alfredo L. ; Pereira, Naveen Luke ; Smith, Byron ; Briasoulis, Alexandros ; Alnsasra, Hilmi ; Kremers, Walter K ; Habermann, Thomas Matthew ; Otley, Clark C. ; Li, Xin ; Edwards, Brooks Sayre ; Stulak, John M. ; Daly, Richard C. ; Kushwaha, Sudhir S. / Incidence of Malignancies in Patients Treated With Sirolimus Following Heart Transplantation. In: Journal of the American College of Cardiology. 2019 ; Vol. 73, No. 21. pp. 2676-2688.
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keywords = "heart transplantation, immunosuppression, malignancy, sirolimus",
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TY - JOUR

T1 - Incidence of Malignancies in Patients Treated With Sirolimus Following Heart Transplantation

AU - Asleh, Rabea

AU - Clavell, Alfredo L.

AU - Pereira, Naveen Luke

AU - Smith, Byron

AU - Briasoulis, Alexandros

AU - Alnsasra, Hilmi

AU - Kremers, Walter K

AU - Habermann, Thomas Matthew

AU - Otley, Clark C.

AU - Li, Xin

AU - Edwards, Brooks Sayre

AU - Stulak, John M.

AU - Daly, Richard C.

AU - Kushwaha, Sudhir S.

PY - 2019/6/4

Y1 - 2019/6/4

N2 - 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.

AB - 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.

KW - heart transplantation

KW - immunosuppression

KW - malignancy

KW - sirolimus

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