Nivolumab + Tacrolimus + Prednisone ± Ipilimumab for Kidney Transplant Recipients With Advanced Cutaneous Cancers.

PURPOSE: Cancer-related mortality rates among kidney transplant recipients (KTR) are high, but these patients have largely been excluded from trials of immune checkpoint inhibitors because of immunosuppression and risk of treatment-related allograft loss (TRAL). We conducted a prospective clinical trial testing nivolumab (NIVO) + tacrolimus (TACRO) + prednisone (PRED) ± ipilimumab (IPI) in KTR with advanced cutaneous cancers. METHODS: Adult KTR with advanced melanoma or basal, cutaneous squamous, or Merkel cell carcinomas were eligible. Immunosuppression was standardized to TACRO (serum trough 2-5 ng/mL) + PRED 5 mg once daily. Patients then received NIVO 480 mg IV once every 4 weeks. The primary composite end point was partial or complete (tumor) response (CR) or stable disease per RECIST v1.1 without allograft loss at 16W. Patients with progressive disease (PD) could receive IPI 1 mg/kg IV + NIVO 3 mg/kg once every 3 weeks × 4 followed by NIVO. Donor-derived cell-free DNA (dd-cfDNA) levels were measured approximately once every 2 weeks as a potential predictor of allograft rejection. RESULTS: Among eight evaluable patients, none met the trial's primary end point. All eight patients experienced PD on NIVO + TACRO + PRED; TRAL occurred in one patient. Six patients then received IPI + NIVO + TACRO + PRED. Best overall responses: two CR (one with TRAL) and four PD (one with TRAL). In total, 7 of 8 pre-NIVO tumor biopsies contained a paucity of infiltrating immune cells. In total, 2 of 5 on-NIVO biopsies demonstrated moderate immune infiltrates; both patients later experienced a CR to IPI + NIVO. In 2 of 3 patients with TRAL, dd-cfDNA elevations occurred 10 and 15 days before increases in serum creatinine. CONCLUSION: In most KTR with advanced skin cancer, TACRO + PRED provides insufficient allograft protection and compromises immune-mediated tumor regression after administration of NIVO ± IPI. Elevated dd-cfDNA levels can signal treatment-related allograft rejection earlier than rises in serum creatinine.

Consensus-Based Recommendations on the Prevention of Squamous Cell Carcinoma in Solid Organ Transplant Recipients: A Delphi Consensus Statement.

IMPORTANCE: There is a paucity of evidence to guide physicians regarding prevention strategies for cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients (SOTRs). OBJECTIVE: To examine the development and results of a Delphi process initiated to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs. EVIDENCE REVIEW: Dermatologists with more than 5 years' experience treating SOTRs were invited to participate. A novel actinic damage and skin cancer index (AD-SCI), consisting of 6 ordinal stages corresponding to an increasing burden of actinic damage and CSCC, was used to guide survey design. Three sequential web-based surveys were administered from January 1, 2019, to December 31, 2020. Pursuant to Delphi principles, respondents thoroughly reviewed all peer responses between rounds. Supplemental questions were also asked to better understand panelists' rationale for their responses. FINDINGS: The Delphi panel comprised 48 dermatologists. Respondents represented 13 countries, with 27 (56%) from the US. Twenty-nine respondents (60%) were Mohs surgeons. Consensus was reached with 80% or higher concordance among respondents when presented with a statement, question, or management strategy pertaining to prevention of CSCC in SOTRs. A near-consensus category of 70% to less than 80% concordance was also defined. The AD-SCI stage-based recommendations were established if consensus or near-consensus was achieved. The panel was able to make recommendations for 5 of 6 AD-SCI stages. Key recommendations include the following: cryotherapy for scattered actinic keratosis (AK); field therapy for AK when grouped in 1 anatomical area, unless AKs are thick in which case field therapy and cryotherapy were recommended; combination lesion directed and field therapy with fluorouracil for field cancerized skin; and initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple skin cancers at a high rate (10 CSCCs per year) or develop high-risk CSCC (defined by a tumor with approximately ≥20% risk of nodal metastasis). No consensus recommendation was achieved for SOTRs with a first low risk CSCC. CONCLUSIONS AND RELEVANCE: Physicians may consider implementation of panel recommendations for prevention of CSCC in SOTRs while awaiting high-level-of-evidence data. Additional clinical trials are needed in areas where consensus was not reached.

Community Testing and SARS-CoV-2 Rates for Latinxs in Baltimore.

INTRODUCTION: Latinxs have been disproportionately impacted by COVID-19. Latinx immigrants, in particular, face significant barriers to SARS-CoV-2 testing, including lack of insurance, language barriers, stigma, work conflicts, and limited transportation. METHODS: In response to a disproportionately high SARS-CoV-2 positivity rate among Latinxs at the Johns Hopkins Health System, investigators implemented free community-based testing by partnering with religious leaders and leveraging the skill of trusted community health workers. Data were extracted from the electronic health record and a Research Electronic Data Capture database. SARS-CoV-2 positivity was evaluated per event stratified by race/ethnicity. Total rates of SARS-CoV-2 positivity and categorical patient characteristics were compared between groups using chi-square tests. RESULTS: Between June 25, 2020 and October 15, 2020, a total of 1,786 patients (57.5% Latinx, 31.2% non-Hispanic White, 5.9% non-Hispanic Black, and 5.3% non-Hispanic other) were tested for SARS-CoV-2 in 18 testing events. Among them, 355 (19.9%) tested positive. The positivity rate was 31.5% for Latinxs, 7.6% for non-Hispanic Blacks, 3.4% for non-Hispanic Whites, and 5.3% for patients of other races/ethnicities. Compared with Latinxs who tested negative, Latinxs who tested positive were more likely to report Spanish as their preferred language (91.6% vs 81.7%, p<0.001), be younger (30.4 vs 33.4 years, p<0.008), and have a larger household size (4.8 vs 4.3 members, p<0.002). CONCLUSIONS: Community-based testing identified high levels of ongoing SARS-CoV-2 transmission among primarily Latinxs with limited English proficiency. During this period, the overall positivity rate at this community testing site was almost 10 times higher among Latinxs than among non-Hispanic Whites.

Kidney retransplantation after anti-programmed cell death-1 (PD-1)-related allograft rejection.

In this report, we describe the first kidney retransplantation performed after anti-programmed cell death-1 (PD-1)-related allograft rejection. In 2014, we administered pembrolizumab (anti-PD-1) for ~9 months to a 57-year-old kidney transplant recipient with metastatic cutaneous squamous cell carcinoma (CSCC). The patient experienced both a complete antitumor response and T cell-mediated allograft rejection requiring reinitiation of hemodialysis. Four-and-a-half years after initiating pembrolizumab, the patient remained without evidence of CSCC relapse and received a kidney transplant from a living-unrelated donor. Ten-and-a-half months after kidney retransplantation, the allograft is functioning well and the patient's CSCC remains in remission. This case illustrates the potential for PD-1 blockade to bring about durable immune-mediated tumor control in chronically immunosuppressed patients, and begins to address the feasibility of kidney retransplantation in patients who have previously received immune checkpoint inhibitor therapy for cancer. Results from this and future cases may help elucidate mechanisms of antitumor immunity and allograft tolerance, and inform updates to transplant decision models. Our report also underscores the need for clinical trials testing novel immunotherapy combinations in solid organ transplant recipients designed to uncouple antitumor and anti-allograft immunity.

Cutaneous Complications in Recipients of Lung Transplants: A Pictorial Review.

Lung transplant is now an established modality for a broad spectrum of end-stage pulmonary diseases. According to the International Society for Heart and Lung Transplantation Registry, more than 50,000 lung transplants have been performed worldwide, with nearly 11,000 recipients of lung transplants alive in the United States. With the increasing use of lung transplant, pulmonologists must be cognizant of the common as well as the unique posttransplant dermatologic complications. Immunosuppression, infections, and a variety of medications and environmental exposures can contribute to these complications. This review aims to provide representative pictures and describe the pathogenesis, epidemiologic characteristics, and clinical manifestations of dermatologic complications encountered among recipients of lung transplants.

Adapalene 0.3% Gel Shows Efficacy for the Treatment of Atrophic Acne Scars.

INTRODUCTION: Scarring is an unfortunate clinical outcome of acne. Current treatment options for atrophic acne scars are dominated by non-pharmacological, invasive procedures which may not be suitable or affordable to all patients. This phase II, single-center, open-label, exploratory study assessed the efficacy, safety and subject-reported outcomes of adapalene 0.3% gel in the treatment of atrophic acne scars. METHODS: The study included subjects aged 18-50 years with past history of acne and moderate to severe facial atrophic acne scars. Subjects received adapalene 0.3% gel once daily for the first 4 weeks and twice daily for the following 20 weeks. Assessments were performed at baseline, day 10 and weeks 4, 8, 16 and 24, and at post-treatment follow-ups (weeks 36 and 48-72). RESULTS: At week 24, investigator and subject assessments reported improvement in skin texture/atrophic scars in 50% and > 80% of subjects, respectively. Subjects were satisfied with the treatment and reported improvements in quality of life. CONCLUSION: Daily use of adapalene 0.3% gel for the treatment of atrophic acne scars showed promising clinical efficacy, a favorable tolerability profile, and improvement in quality of life. FUNDING: Nestlé Skin Health-Galderma R&D. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01213199.

Treatment of human polyomavirus-7-associated rash and pruritus with topical cidofovir in a lung transplant patient: Case report and literature review.

Human polyomavirus-7-associated rash and pruritus (PVARP) is a chronic superficial viral skin infection, which primarily impacts immunocompromised individuals. We report on a case of PVARP in a lung transplant recipient. Our patient developed symptoms 13 years after being on his immunosuppressive regimen, with an insidious course of progressive gray lichenification with marked islands of sparing and quality of life-altering pruritus. Treatment for PVARP is not established; however, topical cidofovir combined with immunomodulation may offer sustained therapeutic benefit.

Eruptive sebaceous hyperplasia as a side effect of oral tacrolimus in a renal transplant recipient.

Sebaceous hyperplasia, a benign proliferation ofsebaceous glands, has been well documented in organ transplant recipients treated with cyclosporine. Sebaceous hyperplasia has not been strongly associated with any other immunosuppressive medications. We report a case of eruptive sebaceous hyperplasia in a renal transplant recipient with no previous exposure to cyclosporine that was recently started on tacrolimus, mycophenolate mofetil, and prednisone. To our knowledge, this is the first report of eruptive sebaceous hyperplasia in a renal transplant recipient who was immunosuppressed with tacrolimus and had no prior exposure to cyclosporine.