Mcc1229, an Stx2a-Amplifying Microcin, Is Produced In Vivo and Requires CirA for Activity.

Enterohemorrhagic Escherichia coli (EHEC) strains, including the foodborne pathogen E. coli O157:H7, are responsible for thousands of hospitalizations each year. Various environmental triggers can modulate pathogenicity in EHEC by inducing the expression of Shiga toxin (Stx), which is encoded on a lambdoid prophage and transcribed together with phage late genes. Cell-free supernatants of the sequence type 73 (ST73) E. coli strain 0.1229 are potent inducers of Stx2a production in EHEC, suggesting that 0.1229 secretes a factor that activates the SOS response and leads to phage lysis. We previously demonstrated that this factor, designated microcin 1229 (Mcc1229), was proteinaceous and plasmid-encoded. To further characterize Mcc1229 and support its classification as a microcin, we investigated its regulation, determined its receptor, and identified loci providing immunity. The production of Mcc1229 was increased upon iron limitation, as determined by an enzyme-linked immunosorbent assay (ELISA), lacZ fusions, and quantitative real-time PCR (qRT-PCR). Spontaneous Mcc1229-resistant mutants and targeted gene deletion revealed that CirA was the Mcc1229 receptor. TonB, which interacts with CirA in the periplasm, was also essential for Mcc1229 import. Subcloning of the Mcc1229 plasmid indicated that Mcc activity was neutralized by two open reading frames (ORFs), each predicted to encode a domain of unknown function (DUF)-containing protein. In a germfree mouse model of infection, colonization with 0.1229 suppressed subsequent colonization by EHEC. Although Mcc1229 was produced in vivo, it was dispensable for colonization suppression. The regulation, import, and immunity determinants identified here are consistent with features of other Mccs, suggesting that Mcc1229 should be included in this class of small molecules.

Status of Cancer Care at Network Sites of the Nation's Academic Cancer Centers.

BACKGROUND: Cancer care coordination across major academic medical centers and their networks is evolving rapidly, but the spectrum of organizational efforts has not been described. We conducted a mixed-methods survey of leading cancer centers and their networks to document care coordination and identify opportunities to improve geographically dispersed care. METHODS: A mixed-methods survey was sent to 91 cancer centers in the United States and Canada. We analyzed the number and locations of network sites; access to electronic medical records (EMRs); clinical research support and participation at networks; use of patient navigators, care paths, and quality measures; and physician workforce. Responses were collected via Qualtrics software between September 2017 and December 2018. RESULTS: Of the 69 responding cancer centers, 74% were NCI-designated. Eighty-seven percent of respondents were part of a matrix health system, and 13% were freestanding. Fifty-six reported having network sites. Forty-three respondents use navigators for disease-specific populations, and 24 use them for all patients. Thirty-five respondents use ≥1 types of care path. Fifty-seven percent of networks had complete, integrated access to their main center's EMRs. Thirty-nine respondents said the main center provides funding for clinical research at networks, with 22 reporting the main center provides all funding. Thirty-five said the main center provided pharmacy support at the networks, with 15 indicating the main center provides 100% pharmacy support. Certification program participation varied extensively across networks. CONCLUSIONS: The data show academic cancer centers have extensive involvement in network cancer care, often extending into rural communities. Coordinating care through improved clinical trial access and greater use of patient navigation, care paths, coordinated EMRs, and quality measures is likely to improve patient outcomes. Although it is premature to draw firm conclusions, the survey results are appropriate for mapping next steps and data queries.

Metastatic melanoma with dedifferentiation and extensive rhabdomyosarcomatous heterologous component.

Melanoma may undergo dedifferentiation and sarcomatous transformation with loss of melanocytic markers. Dedifferentiated melanoma rarely forms true rhabdomyoblasts with skeletal muscle immunophenotype (rhabdomyosarcomatous heterologous component). A 52-year-old woman was diagnosed with invasive melanoma (Breslow thickness 0.83 mm) of the upper back in 2012, treated by wide local excision only. In 2013, an axillary mass was excised to show metastatic melanoma with 2 morphologies: an epithelioid morphology expressing S100 and MART-1 and a spindled morphology with loss of melanocytic markers but strong expression of desmin. This metastasis was found to have BRAF V600E mutation. In 2015, a thoracic epidural mass biopsy showed atypical spindle cells with focal HMB-45 but essentially no S100 expression. Numerous rhabdomyoblasts, some with striations that were strongly positive for desmin and myogenin, were present. In 2016, a right nephrectomy was performed for metastasis to the kidney, and showed sheets of spindle cells and rhabdomyoblasts expressing desmin and myogenin but not S100. Only focal areas demonstrated expression of HMB-45 and SOX-10, supporting the melanocytic origin of the tumor. The numerous rhabdomyoblasts and the loss of S100 expression in the metastatic lesions in this case could have easily led to misdiagnosis if the clinical history was not known.

Do checkpoint inhibitors rely on gut microbiota to fight cancer?

The field of gut microbiota is of growing interest, especially in the recent discoveries of its interaction with host immune responses, which when disrupted, can further alter immunity. It also plays a role in cancer development, its microenvironment and response to anticancer therapeutics. Several recently published experimental studies had explored the efficacy of modifying microbiota to enhance the response of checkpoint inhibitors, suggesting its beneficial function in cancer management and potential to be targeted as a therapeutic agent to enhance efficacy of checkpoint inhibitors. Here we review available evidence, mechanisms and hypotheses of its use to enhance cancer response.

Cancer patient perspectives regarding preparedness for end-of-life care: A qualitative study.

PURPOSE: The extent to which patients feel prepared for end-of-life (EOL) may be associated with important clinical outcomes. Despite growing interest in the concept of "preparedness," however, there is insufficient information about what cancer patients actually need to feel prepared. Such information is foundational for patient-centered care, theory-building, and instrument development. DESIGN: This qualitative study examined patient perspectives regarding preparedness for EOL care. PARTICIPANTS AND METHODS: In-depth interviews were conducted with patients with advanced malignancies and limited life expectancies. Participants were drawn from a large academic cancer center and had a diverse range of malignancies. Thematic text analysis was used to analyze the data. FINDINGS: Six overarching themes emerged. These included readiness to manage concerns about: (1) EOL planning (e.g., goals of care, location of care); (2) interactions with healthcare providers (e.g., communication, symptom control); (3) interactions with family/friends (e.g., perceived burden, support); (4) emotional well-being (e.g., existential distress, fulfillment); (5) spiritual well-being (e.g., spiritual comfort, congregational support); and (6) financial well-being (e.g., medical expenses, estate planning). CONCLUSIONS: Findings highlight areas that patients themselves regard as critical for a sense of preparedness for EOL care. Participants emphasized broader concerns than those previously construed as facets of patient preparedness, and these domains offer modifiable targets for intervention.

Integrating Collaborative Learning and Competition in a Hematology/Oncology Training Program.

New educational methods and structures to improve medical education are needed to face the challenge of an exponential increase and complexity of medical knowledge. Collaborative learning has been increasingly used in education, but its use in medical training programs is in its infancy, and its impact is still unknown; the role of competition in education is more controversial. We introduced these pedagogical methods to the hematology/oncology fellowship program at the University of Arkansas for Medical Sciences to improve attendance and performance at didactic activities and different educational outcomes. One year after the adoption of these methods, the fellowship program has reached many of the expected goals from this intervention without the negative consequences of competition observed in younger learners. The most important conclusion of this project is that collaboration and cross-generational team work provide a healthy and effective learning environment and competition may not add further benefit. Analysis, interpretation, and discussion of our experience are provided. This study was approved by the University of Arkansas for Medical Sciences IRB as a low risk educational intervention not requiring a consent form.

Response of metastatic mucosal melanoma to immunotherapy: It can get worse before it gets better.

Immune therapy with checkpoint inhibitors has revolutionized the management of metastatic melanoma. Ipilimumab, nivolumab, and pembrolizumab are all FDA-approved immune checkpoint inhibitors to treat metastatic melanoma. Responses to immune checkpoint inhibitors are usually delayed. An interim progression on restaging computed tomography scans "pseudo-progression" may be observed before response to treatment occur. In this case, we report a significant interim progression of metastatic mucosal melanoma before meaningful responses to immunotherapy occurred. The patient developed significant immune therapy-related colitis and new onset vitiligo. Further restaging computed tomography scans showed sustained tumor response despite stopping the immune therapy.

Sarcoidosis-like syndrome and lymphadenopathy due to checkpoint inhibitors.

Immunotherapy with checkpoint inhibitors has revolutionized the management of metastatic melanoma. These checkpoints, namely the cytotoxic T lymphocyte antigen 4 and the programmed T cell death 1 receptor, possess an inhibitory effect on the T cell function. Pharmacologic inhibition of cytotoxic T lymphocyte antigen 4 with ipilimumab and programmed T cell death 1 with either pembrolizumab or nivolumab has resulted in long-term sustained responses among patients with metastatic melanoma. The adverse events of these medications are predominantly immune related. Sarcoidosis-like syndrome/lymphadenopathy represents a challenging adverse event to the oncologist as it can be mistaken for progressive disease. Hence, awareness of such adverse event and obtaining a biopsy of the enlarged lymph nodes will confirm the diagnosis and avoid the unnecessary change of current therapies for those with stage IV disease or adding new ones for those with stage III disease. We report three cases of immunotherapy-related sarcoidosis-like syndrome/lymphadenopathy; two cases occurred during adjuvant ipilimumab for stage III surgically resected melanoma and one case during pemprolizumab for stage IV metastatic melanoma.

Human papillomavirus type 16 viral load is decreased following a therapeutic vaccination.

In the dose-escalation phase of a Phase I clinical trial in which six subjects each were vaccinated with PepCan at the 50, 100, 250, and 500 µg per peptide dose, the 50 µg dose showed the best histological regression rate. Ten additional subjects were vaccinated at this dose in the final dose phase. As with the dose-escalation phase, no dose-limiting toxicities were observed. Overall, the histological regression rates were 50% at the 50 µg dose (7 of 14) and 100 µg dose (3 of 6), and 45 % overall (14 of 31). Of subjects in whom HPV type 16 (HPV 16) was detected at entry, it became undetectable in three subjects after vaccination, and the viral loads significantly decreased in nine subjects in whom HPV 16 infection was detected at entry and exit (p = 0.008). Immune profiling revealed increased T-helper type 1 cells after vaccinations (p = 0.02 and 0.0004 after 2 and 4 vaccinations, respectively). T-helper type 2 cells initially increased after two vaccinations (p = 0.01), but decreased below the baseline level after four vaccinations although not significantly. Pre-vaccination regulatory T cell levels were significantly lower in histological responders compared to non-responders (p = 0.03). Feasibility of testing plasma for multiplex cytokine/chemokine analysis and of performing proteomic analysis of PBMCs was examined for potentially identifying biomarkers in the future. While these analyses are feasible to perform, attention needs to be given to how soon the blood samples would be processed after phlebotomy. As sufficient safety of PepCan has been demonstrated, enrollment for the Phase II clinical trial has been opened.

Ipilimumab-Induced Gastrointestinal Toxicities: A Management Algorithm.

Ipilimumab is a cytotoxic T-lymphocyte-associated antigen-4-blocking monoclonal antibody, which has shown a significant survival benefit in metastatic melanoma patients. Despite being a promising therapy for a disease with an otherwise rather dismal prognosis, it is associated with several immune-related adverse effects (IRAE) mainly targeted toward the digestive tract, skin, liver, and hypothalamic-pituitary axis. Ipilimumab-induced gastrointestinal toxicity (IGT) include diarrhea (~44 %), colitis (~18 %), bowel perforation (<1 %), and pancreatitis (<1.5 %). Early recognition of IRAE and treatment initiation are critical to decrease the risk of further complications. Management included steroids as initial therapy, followed by infliximab (anti-tumor necrosis factor alpha antibody) and/or surgical option for complications like bowel perforation. We present a series of three patients with metastatic melanoma, who received treatment with ipilimumab, and presented with varying gastrointestinal clinical manifestations and complications. Through this case series, our attempt is to make practicing gastroenterologists cognizant about the wide spectrum of gastrointestinal toxicity of this rather new clinical entity, as well as to discuss management algorithm for IGT.

Ipilimumab-induced necrotic myelopathy in a patient with metastatic melanoma: A case report and review of literature.

Ipilimumab is a novel humanized monoclonal antibody directed against cytotoxic T lymphocyte antigen 4, a T-cell surface molecule involved in down-regulation and suppression of the T cell response to stimuli. Patients treated with ipilimumab are at risk for immune-related adverse events involving the skin, digestive tract, liver and endocrine organs. Few case reports of immune-related adverse effects involving central or peripheral nervous system due to ipilimumab are published. These include inflammatory myopathy, aseptic meningitis, severe meningo-radiculo-neuritis, temporal arteritis, Guillain-Barre syndrome, and posterior reversible encephalopathy syndrome. We report the first case of ipilimumab-induced progressive necrotic myelopathy.

An adverse event capture and management system for cancer studies.

BACKGROUND: Comprehensive capture of Adverse Events (AEs) is crucial for monitoring for side effects of a therapy while assessing efficacy. For cancer studies, the National Cancer Institute has developed the Common Terminology Criteria for Adverse Events (CTCAE) as a required standard for recording attributes and grading AEs. The AE assessments should be part of the Electronic Health Record (EHR) system; yet, due to patient-centric EHR design and implementation, many EHR's don't provide straightforward functions to assess ongoing AEs to indicate a resolution or a grade change for clinical trials. METHODS: At UAMS, we have implemented a standards-based Adverse Event Reporting System (AERS) that is integrated with the Epic EHR and other research systems to track new and existing AEs, including automated lab result grading in a regulatory compliant manner. Within a patient's chart, providers can launch AERS, which opens the patient's ongoing AEs as default and allows providers to assess (resolution/ongoing) existing AEs. In another tab, it allows providers to create a new AE. Also, we have separated symptoms from diagnoses in the CTCAE to minimize inaccurate designation of the clinical observations. Upon completion of assessments, a physician would submit the AEs to the EHR via a Health Level 7 (HL7) message and then to other systems utilizing a Representational State Transfer Web Service. CONCLUSIONS: AERS currently supports CTCAE version 3 and 4 with more than 65 cancer studies and 350 patients on those studies. This type of standard integrated into the EHR aids in research and data sharing in a compliant, efficient, and safe manner.

Rituximab and intermediate-purity plasma-derived factor VIII concentrate (Koate®) as adjuncts to therapeutic plasma exchange for thrombotic thrombocytopenic purpura in patients with an ADAMTS13 inhibitor.

Thrombotic thrombocytopenic purpura (TTP) results from a congenital or acquired deficiency of the von Willebrand factor (vWF)-cleaving protease ADAMTS13. The disease can be fatal and hence treatment should be initiated promptly. Therapeutic plasma exchange (TPE) remains the standard treatment along with adjunct therapies including steroids and immunosuppressive drugs. Addition of rituximab to TPE has been shown to be beneficial in refractory/relapsing TTP; however, TPE results in removal of rituximab from the circulation requiring more frequent dosing of rituximab to achieve a favorable outcome. The intermediate-purity plasma-derived Factor VIII concentrate (FVIII) Koate® contains the highest amount of ADAMTS13 activity yet reported and has been used successfully in treating congenital TTP. Here we report our experience with addition of this FVIII concentrate to rituximab, corticosteroids and TPE in three TTP patients with an ADAMTS13 inhibitor to permit withholding TPE for 48 h after rituximab infusion.

Treatment of metastatic melanoma with pazopanib: A report of five patient cases.

Metastatic melanoma has a median length of survival after diagnosis of 6-9 months. Unfortunately, the National Comprehensive Cancer Network clinical practice guidelines for treating stage IV, unresectable, metastatic melanoma are limited with regard to treatment options. Pazopanib (Votrient™) is FDA-approved for advanced soft tissue sarcoma and advanced renal cell carcinoma. Limited research exists for using pazopanib in the treatment of metastatic melanoma. We present five cases in which pazopanib was used in combination with paclitaxel ± carboplatin for treatment of unresectable, metastatic melanoma.

Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma.

Romidepsin (depsipeptide or FK228) is a histone deacetylase inhibitor, one of a new class of agents active in T-cell lymphoma. A phase 2 trial was conducted in cutaneous (CTCL) and peripheral (PTCL) T-cell lymphoma. Major and durable responses in CTCL supported the approval of romidepsin for CTCL. Forty-seven patients with PTCL of various subtypes including PTCL NOS, angioimmunoblastic, ALK-negative anaplastic large cell lymphoma, and enteropathy-associated T-cell lymphoma were enrolled. All patients had received prior therapy with a median of 3 previous treatments (range 1-11); 18 (38%) had undergone stem-cell transplant. All patients were evaluated for toxicity; 2 patients discovered to be ineligible were excluded from response assessment. Common toxicities were nausea, fatigue, and transient thrombocytopenia and granulocytopenia. Complete responses were observed in 8 and partial responses in 9 of 45 patients, for an overall response rate of 38% (95% confidence interval 24%-53%). The median duration of overall response was 8.9 months (range 2-74). Responses were observed in various subtypes, with 6 responses among the 18 patients with prior stem-cell transplant. The histone deacetylase inhibitor romidepsin has single agent clinical activity associated with durable responses in patients with relapsed PTCL.

Consistency Between State's Cancer Registry and All-Payer Claims Database in Documented Radiation Therapy Among Patients Who Received Breast Conservative Surgery.

PURPOSE: Arkansas is one of only four known states that have linked All-Payer Claims Database (APCD) to state's cancer registry (Arkansas Cancer Registry [ACR]). We evaluated the reporting consistency of radiation therapy (RT) between the two sources. METHODS: Women age ≥ 18 years diagnosed in 2013-2017 with early-stage hormone receptor-positive breast cancer who received breast-conserving surgery were identified. Patients must have continuous insurance coverage (any private plans, Medicaid, and Medicare) in the 13 months (month of diagnosis and 12 months after). Receipt of RT was identified independently from ACR and APCD. We calculated sensitivity, specificity, positive predictive value, and negative predictive value for receipt of RT coded by the registry compared with APCD billing claims as the gold standard. We assessed the degree of concordance between the data sources by Cohen's kappa statistics. RESULTS: The final sample included 2,695 patients who were in both databases and satisfied our inclusion/exclusion criteria. Using APCD as the gold standard, there were high sensitivity (88.1%) and positive predictive value (87.7%) and moderate specificity (71.1%) and negative predictive value (71.8%). The overall agreement between the two sources was 83.0%, with a kappa statistic of 0.59 (95% CI, 0.56 to 0.63). Consistency measures varied by age, stage, and insurance type with Medicare fee-for-service coverage only having the best and private insurance only the worse consistency. CONCLUSION: In patients with early-stage hormone receptor-positive breast cancer who received breast-conserving surgery, recording of RT receipt was moderately consistent between Arkansas APCD and ACR. Future studies are needed to identify factors affecting reporting consistency to better use this unique resource in addressing population health problems.

A prospective analysis of the influence of older age on physician and patient decision-making when considering enrollment in breast cancer clinical trials (SWOG S0316).

PURPOSE: Patients older than 65 years are underrepresented in clinical trials. We conducted a prospective study (SWOG S0316) to determine physician- and patient-perceived barriers to breast cancer clinical trial enrollment for older patients. METHODS: Eight geographically diverse SWOG institutions participated. The study assessed patients' and physicians' decisions to enroll in or decline clinical treatment trials, including demographics, trial availability, and eligibility. Patient and physician questionnaires elicited concerns related to treatment, medical status, age, family, and financial or transportation concerns. RESULTS: A total of 1,079 patients were registered and eligible and 909 (84%) returned for follow-up. The major reason for nonaccrual was either trial unavailability or ineligibility (60%). Older patients were less likely to be eligible for trials (65% for age ≥65 years vs. 78% for age <65 years). If eligible, trial participation rates did not differ significantly by age (34% for age ≥65 years vs. 40% for age <65 years). Patients ≥65 years more often were concerned about side effects, had friends opposed to participation, or believed that participation would not benefit other generations. When trials were available and patients were eligible, physicians discussed trial participation with 76% of patients <65 years versus 58% of patients ≥65 years of age. For patients ≥65 years, 11% of physicians indicated age as a reason they did not enroll a patient in a clinical trial. CONCLUSION: Trial unavailability or patient ineligibility were the major reasons for lack of enrollment in breast cancer clinical trials for patients of all ages in this prospective study. Older patients were less likely to be eligible for trials, but if eligible they participated at similar rates to younger patients.

Immune adverse events (irAEs) with adjuvant ipilimumab in melanoma, use of immunosuppressants and association with outcome: ECOG-ACRIN E1609 study analysis.

BACKGROUND: The impact of immune-related adverse events (irAEs) occurring from adjuvant use of immunotherapy and of their management on relapse-free survival (RFS) and overall survival (OS) outcomes is currently not well understood. PATIENTS AND METHODS: E1609 enrolled 1673 patients with resected high-risk melanoma and evaluated adjuvant ipilimumab 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus interferon-α. We investigated the association of irAEs and of use of immunosuppressants with RFS and OS for patients treated with ipilimumab (n=1034). RESULTS: Occurrence of grades 1-2 irAEs was associated with RFS (5 years: 52% (95% CI 47% to 56%) vs 41% (95% CI 31% to 50%) with no AE; p=0.006) and a trend toward improved OS (5 years: 75% (95% CI 71% to 79%) compared with 67% (95% CI 56% to 75%) with no AE; p=0.064). Among specific irAEs, grades 1-2 rash was most significantly associated with RFS (p=0.002) and OS (p=0.003). In multivariate models adjusting for prognostic factors, the most significant associations were seen for grades 1-2 rash with RFS (p<0.001, HR=0.70) and OS (p=0.01, HR=0.71) and for grades 1-2 endocrine+rash with RFS (p<0.001, HR=0.66) and OS (p=0.008, HR=0.7). Overall, grades 1-2 irAEs had the best prognosis in terms of RFS and OS and those with grades 3-4 had less RFS benefits and no OS advantage over no irAE. Patients experiencing grades 3-4 irAE had significantly higher exposure to corticosteroids and immunosuppressants than those with grades 1-2 (92% vs 60%; p<0.001), but no significant associations were found between corticosteroid and immunosuppressant use and RFS or OS. In investigating the impact of non-corticosteroid immunosuppressants, although there were trends toward better RFS and OS favoring cases who were not exposed, no significant associations were found. CONCLUSIONS: Rash and endocrine irAEs were independent prognostic factors of RFS and OS in patients treated with adjuvant ipilimumab. Patients experiencing lower grade irAEs derived the most benefit, but we found no significant evidence supporting a negative impact of high dose corticosteroids and immunosuppressants more commonly used to manage grades 3-4 irAEs.

Manganese superoxide dismutase polymorphism, treatment-related toxicity and disease-free survival in SWOG 8897 clinical trial for breast cancer.

To date, the few studies of associations between a functional polymorphism in the oxidative stress-related gene manganese superoxide dismutase (SOD2) and breast cancer survival have been inconsistent. In a homogeneous patient population from a large cooperative group trial Southwest Oncology Group (SWOG) 8897, we evaluated this polymorphism in relation to both treatment-related toxicity and disease-free survival (DFS). Among 458 women who received cyclophosphamide-containing adjuvant chemotherapy, those with variant C alleles, related to higher antioxidant activity, experienced less grade 3-4 neutropenia (OR = 0.52, 95% CI = 0.29-0.92) but had worse DFS (HR = 1.59, 95% CI = 0.99-2.55) than women with TT genotypes. No associations were observed among 874 women who were followed without adjuvant therapy. Our results are consistent with the hypothesis that women with higher SOD2 antioxidant activity may experience less treatment-related toxicity but shorter time to disease recurrence or death after breast cancer adjuvant chemotherapy, supporting the modifying effects of oxidative stress-related enzymes on cancer treatment toxicity and efficacy.

Immunotherapy Outcomes in Advanced Melanoma in Relation to Age.

INTRODUCTION: Older age is a melanoma risk factor. Elderly individuals are likelier to have immunosenescence, which could help melanoma cells escape immune surveillance. Hence, it is believed that elderly people cannot mount a potent immune response to checkpoint inhibitors to eliminate melanoma. OBJECTIVES: To investigate age-related differences in the time to progression, overall survival, and immunotherapy-related adverse events among patients with metastatic melanoma who received checkpoint inhibitors. METHODS: We retrospectively identified patients at our institution between January 2012 and December 2016 with stage IV melanoma who received at least 1 dose of ipilimumab, pembrolizumab, nivolumab, or combined ipilimumab and nivolumab. Demographic, pathologic, and clinical characteristics were obtained. Immune-related response criteria were used to define responses. RESULTS: Twenty-nine patients were younger than age 65 years and 31 were age 65 years or older. Time to progression was comparable between the age groups (hazard ratio = 0.79, 95% confidence interval = 0.37-1.70, p = 0.46). Overall survival was not significantly different after immunotherapy between groups (hazard ratio = 0.75, 95% confidence interval = 0.31-1.82, p = 0.491). Overall, immunotherapy-related adverse events were comparable between groups, with 62% in younger patients (18/29) and 45% in older patients (14/31 p = 0.19). Of 60 patients, 30 responded to immunotherapy. Nonresponders were more likely than responders to have BRAF-mutated melanomas (16 [53.3%] vs 8 [27.6%]; p = 0.04) and less likely to have immunotherapy-related adverse events (12 [40%] vs 20 [66.7%]; p = 0.04). CONCLUSION: Aging does not seem to affect response to checkpoint inhibitors. Elderly patients with metastatic melanoma should be treated similarly to younger patients.