Infrequently prescribed drug cocktail prolongs survival of lung transplant patients

A combination of sirolimus and tacrolimus was found to significantly improve patient survival in a novel epidemiological analysis of more than 9000 lung transplant patients’ data, compared with more commonly prescribed drug regimes.

Aug 30, 2019
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Whole lung transplants are necessary procedures for patients with end-stage lung diseases. However, patients’ average survival following these risky operations is less than 6 years. In a novel, retrospective, epidemiological analysis, researchers at the University of Maryland School of Medicine (UMSOM; MD, USA) have determined that an infrequently prescribed drug combination of sirolimus and tacrolimus substantially improves transplant recipients’ survival compared with other more commonly supplied drugs.

Organ rejection is the most common cause of transplant failure and patients’ death following transplantation. As a result, transplant recipients are frequently givem immunosuppressant drugs to dampen down their immune responses. However, immunosuppressive drugs can make patients susceptible to various secondary infections and the FDA has yet to recommend or approve a specific drug regime for lung transplant patients.

In this study, researchers analyzed data from the United Network for Organ Sharing (VA, USA) on over 9000 lung transplant patients and categorized the data according to patients prescribed immunosuppressant drug regimens.

Researchers were particularly interested in the survival rates of patients taking sirolimus – a cell cycle checkpoint inhibitor. A limited number of observational studies had previously demonstrated sirolimus to significantly extend lung transplant patients survival.

The survival rates of patients prescribed sirolimus were compared with those of patients who were administered mycophenolate mofetil (MMF) – the most commonly prescribed cell cycle inhibitor.

Frequently asked questions:

The data demonstrated that sirolimus provided a survival advantage of more than 2 years compared with MMF. Marniker Wijesinha, a post-doctoral fellow at UMSOM and first study author, explained: “The survival improvement with sirolimus was driven by fewer deaths from the top three causes: chronic rejection, infections and cancer.”

Often, transplant recipients are prescribed a cocktail of immunosuppressant drugs comprising a cell cycle checkpoint inhibitor alongside steroids – such as tacrolimus.

Researchers observed that patients prescribed a combination of sirolimus and tacrolimus had greater median survival compared with patients given MMF and tacrolimus – average survival lengths of these patient cohorts were 8.9 and 7.1 years respectively.

Despite this, prescription of combination MMF and tacrolimus was more common than of sirolimus and tacrolimus; more than 5000 of the study participants received MMF and tacrolimus compared with approximately 200 patients who were prescribed sirolimus and tacrolimus.

However, sirolimus is known to interfere with wound healing and so its' prescription to patients is often delayed – for up to 1 year – post transplant surgery. To ensure that such delayed prescription did not impact on the study results, researchers accounted for this.

Further, researchers compared the survival rates of patients who received either sirolimus or MMF therapy, alongside tacrolimus and induction therapy. Combination sirolimus and tacrolimus therapy was associated with more than 3 years improved survival compared with patients who received MMF, tacrolimus and induction therapy.

Dean E. Albert Reece, Executive Vice President for Medical Affairs at UMSOM, commented: “This study illustrates the value of searching through large databases to discern patterns and practices that may not be immediately obvious, but can have a major impact on patient care…Further studies of patients undergoing lung transplantation are needed to confirm the findings associated with sirolimus, but this research is a great start.”

Sources:

Wijesinha M, Hirshon JM, Terrin M et al. Survival Associated With Sirolimus Plus Tacrolimus Maintenance Without Induction Therapy Compared With Standard Immunosuppression After Lung Transplant. JAMA Netw Open. 2(8); e1910297. doi:10.1001/jamanetworkopen.2019.10297 (Epub ahead of print) (2019);

https://www.umms.org/ummc/news/2019/extend-lives-of-lung-transplant-patients


What is sirolimus used for?

Sirolimus is commonly used to suppress the immune systems of patients undergoing organ transplantation, most frequently, kidney transplants.

Is sirolimus a chemotherapy?

Sriolimus, also know as rapamycin, is a mammalian Target Of Rapamycin (mTOR) inhibitor. Sirolimus is being investigated for use as an anti-cancer agents, but is not a conventional chemotherapy.

What is induction therapy?

Induction therapy is an optional treatment regime that is used in more than 50% of transplant centers in the USA. Induction therapy involves giving patients high doses of immunosuppressant drugs at the time of their transplant procedure, for up to 14 days. This is in addition to maintenance therapy.



Ilana Landau

Assistant Editor, Future Science Group

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