A Pilot Study of Checkpoint Inhibitors in Solid Organ Transplant Recipients with Metastatic Cutaneous Squamous Cell Carcinoma

Abstract

Background. Immune checkpoint inhibitors (ICIs) are increasingly used in various solid organ malignancies. However, there are limited data regarding their safety and efficacy in solid organ transplant (SOT) recipients. The aim of this study was to review our experience with ICIs in SOT recipients with advanced head and neck cutaneous squamous cell carcinoma (cSCC). Methods. A retrospective review of ICIs used in SOT recipients from April 2011 to September 2019 was undertaken. Patient clinical and demographic features, ICI regimen, immunosuppression, treatment efficacy, and adverse events were reviewed. Results. The seven SOT recipients (four kidney, two liver, one lung) were diagnosed with metastatic head and neck cSCC. All had undergone prior locoregional surgery and adjuvant radiation therapy. At a median of 10.8 years (range, 6.6-18.1) posttransplant, six were treated with cemiplimab and one with pembrolizumab after minimizing calcineurin inhibitors (CNIs) or conversion of CNI to mammalian target of rapamycin (mTOR) inhibitors. During a median follow-up of 7.1 months, overall tumor response rate was 57.1% with one complete responder and three partial responders. Four patients died at a median of 135 days after starting ICI with two dying from tumor progression and two dying from other causes. Regarding adverse events, one lung transplant recipient developed severe pneumonitis that resolved with high-dose steroids, and one renal transplant patient developed progressive renal injury and died of unrelated causes. The three patients who received prophylactic prednisone all responded to cemiplimab with preserved allograft function and no adverse events. Conclusion. Our data suggest that minimization of CNI and conversion of CNI to mTOR inhibitors along with judicious use of prophylactic steroids may allow for the safe use of ICIs in SOT recipients with advanced cSCC. Short-term efficacy appears promising, but prospective studies with further follow-up and a standardized protocol for prophylactic steroids are needed. The Oncologist 2020;25:1-6 Implications for Practice: Solid organ transplant (SOT) recipients are at increased risk of developing malignancy because of long-term post-transplant immunosuppression. Although immune checkpoint inhibitors (ICIs) are increasingly shown to be successful in treating multiple types of cancer, SOT recipients have been excluded from clinical trials because of concerns regarding potential allograft rejection. This pilot study provides evidence that ICIs along with prophylactic steroids may be a safe and efficacious treatment option for selected SOT recipients with advanced cutaneous squamous cell carcinoma. However, further prospective studies using ICIs in this high-risk patient population are needed.

Immunotherapy use outside clinical trial populations: never say never?

“…58 Relatively high risk of rejection with anti-PD-1 was also shown in other reports, [58][59][60][61][62][63][64][65][66] and rates by organ type for this class are shown in Table 3. Renal transplant was the most common allograft type, with rejection rates of 42%-63% with anti-PD-1-based therapy [58][59][60][61][62][63][64][65] and a median time to rejection of 21-24 days from ICI start. 59,61 Underscoring the potentially life-threatening consequences of anti-PD-1 use around transplant, a recent report detailed a case of an HCC patient who underwent liver transplant after 2 years of nivolumab treatment (last dose 8 days before transplantation) and subsequently suffered fatal acute hepatic necrosis in the immediate post-operative period resulting from a profound immune reaction likely enabled by nivolumab.…”

“…58 The highest rejection risk was observed with PD-1 inhibitors [48% (20/ 42) overall; 54% (13/24) nivolumab, 39% (7/18) pembrolizumab], and the lowest with ipilimumab [23% (3/ 13)]. 58 Relatively high risk of rejection with anti-PD-1 was also shown in other reports, [58][59][60][61][62][63][64][65][66] and rates by organ type for this class are shown in Table 3. Renal transplant was the most common allograft type, with rejection rates of 42%-63% with anti-PD-1-based therapy [58][59][60][61][62][63][64][65] and a median time to rejection of 21-24 days from ICI start.…”

Renal Complications Related to Checkpoint Inhibitors: Diagnostic and Therapeutic Strategies

“…Before ICI initiation, it is recommended to perform a precise renal examination with data on urinalysis and eGFR, avoid PPI use, and plan a precise follow-up for early detection of any renal complications. In case of solid organ transplant recipients (SOT), minimization of calcineurin inhibitors (CNIs) and the conversion of CNI to mTOR inhibitors (imTORs) along with judicious use of prophylactic steroids could enable the safe use of ICIs in patients with advanced cutaneous squamous cell carcinoma [ 64 ]. Clinicians should also be aware of the possibility of renal graft rejection, even in failed allografts [ 65 ].…”

Cytokine storm induced by a PD1 inhibitor in a renal transplant patient

“…To our knowledge, this is the first evidence of IL-6, IL-8, and sCD163 elevation after a single dose of PD1 blockade in a transplant patient that mimics sepsis secondary to an infection. The chronology strongly suggests a pharmacological cause and excludes other diagnoses, although successful treatment of renal patients with cemiplimab has previously been reported 5 and small series suggest reasonable safety and efficacy of anti-PD1 in transplant patients. 6 Our findings should underscore the relevance of inflammatory cytokine measurement when irAEs are suspected.…”