Incidence of Malignancies in Patients Treated With Sirolimus Following Heart Transplantation

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

doi:10.1016/j.jacc.2019.03.499

Cited by 42 publications

(42 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mammalian target of rapamycin inhibitors are also commonly used after diagnosis of post‐transplant malignancy to lower the risk of recurrence. There is now evidence that suggests that these drugs decrease the risk of de novo malignancies, post‐transplant lymphoproliferative disorders, and primary occurrences of non‐melanoma skin cancers . Data on delaying recurrence of skin cancer and reducing mortality from non‐skin malignancies are also encouraging …”

Section: Mtor Inhibitors In Heart Transplantationmentioning

confidence: 99%

Recent advances in the role of mammalian target of rapamycin inhibitors on cardiac allograft vasculopathy

Bellumkonda

Patel

2019

Clinical Transplantation

View full text Add to dashboard Cite

Cardiac allograft vasculopathy (CAV) is a progressive fibroproliferative disease, which contributes to significant morbidity and mortality during long-term follow-up after heart transplantation. Mammalian target of rapamycin (mTOR) inhibitors have favorable effects on endothelial function and reduce intimal proliferation, and their early use after transplantation has been associated with a reduction in the risk of development and progression of CAV. However, there are conflicting reports on the efficacy of these agents in treating established CAV. Most of the data until recently have been based on short-term follow-up, and CAV was assessed by changes in intravascular ultrasound. In this study, we review the mechanism of action of mTOR inhibitors and their protective role in CAV and summarize some of the recent literature, which include long-term follow-up using this class of medications. K E Y W O R D Sheart (allograft) function/dysfunction, immunosuppression, mechanistic target of rapamycin, rejection: vascular, vasculopathy

show abstract

Section: Mtor Inhibitors In Heart Transplantationmentioning

confidence: 99%

Recent advances in the role of mammalian target of rapamycin inhibitors on cardiac allograft vasculopathy

Bellumkonda

Patel

2019

Clinical Transplantation

View full text Add to dashboard Cite

show abstract

“…Routine endomyocardial biopsies were performed according to our previously described institutional protocols 10,13 . Each biopsy result was graded and assigned a grading for acute cellular or antibody‐mediated rejection based on ISHLT grading.…”

Section: Methodsmentioning

confidence: 99%

“…Each biopsy result was graded and assigned a grading for acute cellular or antibody‐mediated rejection based on ISHLT grading. Total rejection and any rejection scores were calculated for each patient both at baseline (until the first IVUS examination) and during follow‐up (from the time of first IVUS examination up to the time of last follow‐up) in both groups with and without proteinuria, based on the formulas previously reported by our group 10,13 …”

Section: Methodsmentioning

confidence: 99%

“…In a recent analysis of a retrospective cohort of 402 HT recipients from our institution, treated with CNI‐ or SRL‐based regimens, early conversion to SRL was associated with attenuated progression of cardiac allograft vasculopathy (CAV), lower all‐cause mortality, fatal and nonfatal CAV‐related events, at the expense of increased triglycerides and higher rates of acute cellular rejection compared with CNIs but with similar rates of moderate and severe rejection between groups 10 . Other advantages of conversion to SRL in lieu of CNI maintenance therapy include improvement in kidney function 11,12 and a decrease in rates of malignancy following HT 13 . However, the use of mTOR antagonists can cause or worsen proteinuria, particularly in patients who are converted from a CNI, and proteinuria is usually reversible after withdrawal of SRL 14 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of mTOR inhibitor–related proteinuria on progression of cardiac allograft vasculopathy and outcomes among heart transplant recipients

Asleh

Alnsasra

Lerman

et al. 2021

American Journal of Transplantation

Self Cite

View full text Add to dashboard Cite

We have previously described the use of sirolimus (SRL) as primary immunosuppression following heart transplantation (HT). The advantages of this approach include attenuation of cardiac allograft vasculopathy (CAV), improvement in glomerular filtration rate (GFR), and reduced malignancy. However, in some patients SRL may cause significant proteinuria. We sought to investigate the prognostic value of proteinuria after conversion to SRL. CAV progression and adverse clinical events were studied. CAV progression was assessed by measuring the Δ change in plaque volume (PV) and plaque index (PI) per year using coronary intravascular ultrasound. Proteinuria was defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL. Overall, 137 patients were analyzed (26% with proteinuria). Patients with proteinuria had significantly lower GFR (P = .005) but similar GFR during follow‐up. Delta PV (P < .001) and Δ PI (P = .001) were significantly higher among patients with proteinuria after adjustment for baseline characteristics. Multivariate Cox regression analysis showed higher all‐cause mortality (hazard ratio 3.8; P = .01) with proteinuria but similar risk of CAV‐related events (P = .61). Our results indicate that proteinuria is a marker of baseline renal dysfunction, and that HT recipients who develop proteinuria after conversion to SRL have less attenuation of CAV progression and higher mortality risk.

show abstract

“…The mTOR inhibitors sirolimus and everolimus are immunosuppressive drugs occasionally used in solid organ transplantation and more marginally in haematopoietic stem cell transplantation. In addition to their immunosuppressive effects, many studies have strongly supported their antitumoral effects, and some research groups have strongly suggested switching any immunosuppressive treatment to mTOR inhibitors in the event of post-transplant lymphoproliferative disorders [ 83 , 84 , 85 ]. Activation of the PI3K/AKT/mTOR signalling pathway has been shown in ALPS, thus providing a rationale for targeting this pathway with mTOR inhibitors as this lymphoproliferative disease is associated with malignancy [ 86 , 87 ].…”

Section: Possibilities Of Immunotherapy For Children With Primary mentioning

confidence: 99%

The Possibilities of Immunotherapy for Children with Primary Immunodeficiencies Associated with Cancers

2020

View full text Add to dashboard Cite

Many primary immunodeficiencies (PIDs) are recognised as being associated with malignancies, particularly lymphoid malignancies, which represent the highest proportion of cancers occurring in conjunction with this underlying condition. When patients present with genetic errors of immunity, clinicians must often reflect on whether to manage antitumoral treatment conventionally or to take a more personalised approach, considering possible existing comorbidities and the underlying status of immunodeficiency. Recent advances in antitumoral immunotherapies, such as monoclonal antibodies, antigen-specific adoptive cell therapies or compounds with targeted effects, potentially offer significant opportunities for optimising treatment for those patients, especially with lymphoid malignancies. In cases involving PIDs, variable oncogenic mechanisms exist, and opportunities for antitumoral immunotherapies can be considered accordingly. In cases involving a DNA repair defect or genetic instability, monoclonal antibodies can be proposed instead of chemotherapy to avoid severe toxicity. Malignancies secondary to uncontrolled virus-driven proliferation or the loss of antitumoral immunosurveillance may benefit from antivirus cell therapies or allogeneic stem cell transplantation in order to restore the immune antitumoral caretaker function. A subset of PIDs is caused by gene defects affecting targetable signalling pathways directly involved in the oncogenic process, such as the constitutive activation of phosphoinositol 3-kinase/protein kinase B (PI3K/AKT) in activated phosphoinositide 3-kinase delta syndrome (APDS), which can be settled with PI3K/AKT inhibitors. Therefore, immunotherapy provides clinicians with interesting antitumoral therapeutic weapons to treat malignancies when there is an underlying PID.

show abstract

Incidence of Malignancies in Patients Treated With Sirolimus Following Heart Transplantation

Cited by 42 publications

References 26 publications

Recent advances in the role of mammalian target of rapamycin inhibitors on cardiac allograft vasculopathy

Recent advances in the role of mammalian target of rapamycin inhibitors on cardiac allograft vasculopathy

Effects of mTOR inhibitor–related proteinuria on progression of cardiac allograft vasculopathy and outcomes among heart transplant recipients

The Possibilities of Immunotherapy for Children with Primary Immunodeficiencies Associated with Cancers

Contact Info

Product

Resources

About