Efficacy and tolerance of immune checkpoint inhibitors in transplant patients with cancer: A systematic review

Abstract

Solid organ transplant (SOT) is frequently complicated by cancers, which render immunosuppression challenging. Immune checkpoint inhibitors have emerged as treatments for many cancers. Data are lacking regarding efficacy and rejection risk in the SOT population. We conducted a systematic literature review and analyzed 83 cases of immune checkpoint inhibitor use for cancer in SOT. Two thirds of these patients received anti–programmed death ligand 1 therapy, 15.7% received anti–cytotoxic T lymphocyte–associated protein 4 therapy, and 10.8% received a combination. Allograft rejection occurred in 39.8% of patients, leading to end‐stage organ failure in 71.0% of cases. Outcomes were similar across organs and immunotherapy regimens. The use of immunosuppressants other than steroids, time since transplant, and prior episodes of rejection were associated with the risk of rejection. The median overall survival of patients was 36 weeks. Most of the deaths were related to cancer progression. In nonkidney recipients, graft rejection was strongly associated with worse survival. At the end of the study, 19.3% of the patients were alive, free from rejection and tumor progression. This study highlights the difficult tradeoff facing oncologists and transplant specialists managing transplant recipients with cancer, and the need for prospective data and novel biomarkers for identifying the patients likely to benefit from immunotherapy in the SOT setting.

Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients

“…16 17 While multiple case reports and series of single agent checkpoint blockade in SOTRs exist, 18 few cases treated with concurrent ipilimumab and anti-PD1 therapy have been reported. [19][20][21] This patient exhibited partial response; however, graft rejection developed 21 days after treatment initiation. 21 Here, we present four cases of metastatic cutaneous malignancy in the setting of kidney transplant treated with combination ipilimumab and nivolumab immunotherapy.…”

“…More recently, a larger systematic review reported 83 SOTRs treated with immunotherapy (two-thirds anti-PD1/PDL1, 15.7% anti-CTLA-4, and 10.8% combination therapy either sequentially or simultaneously). 20 This included 53 kidney, 24 liver, and six heart transplants with similar rejection rates across organs and checkpoint inhibitors. Time since transplantation of at least 8 years was associated with lower risk of graft rejection, and history of prior allograft rejection was associated with higher risk.…”

Transplant-associated cancer in the era of immune checkpoint inhibitors: Primum non nocere

“…D’Izarny‐Gargas et al 4 conducted a systematic literature review and analysis of 83 cases of CPI use for cancer in solid organ transplant recipients. The cancers reported for these patients included melanoma (46 cases), hepatocellular carcinoma (12 cases), and cutaneous squamous cell carcinoma (10 cases).…”

Hepatocellular Carcinoma—The Influence of Immunoanatomy and the Role of Immunotherapy

“…Immunosuppression, a requirement after transplant, has historically excluded the transplant population from clinical trials using immunotherapy due to concerns for decreased efficacy and increased harm in this patient population using this modality. PD-1 inhibitors were contraindicated in patients with previous solid organ transplantation as there is a documented risk of organ rejection, quoted to be 37.5% in liver transplants, in a systematic review [ 133 ]. However, more recently, there have been case reports suggesting a benefit in the use of PD-1 inhibitors in this population [ 134 , 135 ].…”