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Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience.

ABSTRACT: Uveal melanoma exhibits a high incidence of metastases; and, to date, there is no systemic therapy that clearly improves outcomes. The anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab is a standard of care for metastatic melanoma; however, the clinical activity of CTLA-4 inhibition in patients with metastatic uveal melanoma is poorly defined.To assess ipilimumab in this setting, the authors performed a multicenter, retrospective analysis of 4 hospitals in the United States and Europe. Clinical characteristics, toxicities, and radiographic disease burden, as determined by central, blinded radiology review, were evaluated.Thirty-nine patients with uveal melanoma were identified, including 34 patients who received 3 mg/kg ipilimumab and 5 who received 10 mg/kg ipilimumab. Immune-related response criteria and modified World Health Organization criteria were used to assess the response rate (RR) and the combined response plus stable disease (SD) rate after 12 weeks, after 23 weeks, and overall (median follow-up, 50.4 weeks [12.6 months]). At week 12, the RR was 2.6%, and the response plus SD rate was 46.%; at week 23, the RR was 2.6%, and the response plus SD rate was 28.2%. There was 1 complete response and 1 late partial response (at 100 weeks after initial SD) for an immune-related RR of 5.1%. Immune-related adverse events were observed in 28 patients (71.8%) and included 7 (17.9%) grade 3 and 4 events. Immune-related adverse events were more frequent in patients who received 10 mg/kg ipilimumab than in those who received 3 mg/kg ipilimumab. The median overall survival from the first dose of ipilimumab was 9.6 months (95% confidence interval, 6.3-13.4 months; range, 1.6-41.6 months). Performance status, lactate dehydrogenase level, and an absolute lymphocyte count ? 1000 cells/?L at week 7 were associated significantly with survival.In this multicenter, retrospective analysis of 4 hospitals in the United States and Europe of patients with uveal melanoma, durable responses to ipilimumab and manageable toxicity were observed.

SUBMITTER: Luke JJ

PROVIDER: S-EPMC3986037 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience.

Luke Jason J JJ Callahan Margaret K MK Postow Michael A MA Romano Emanuela E Ramaiya Nikhil N Bluth Mark M Giobbie-Hurder Anita A Lawrence Donald P DP Ibrahim Nageatte N Ott Patrick A PA Flaherty Keith T KT Sullivan Ryan J RJ Harding James J JJ D'Angelo Sandra S Dickson Mark M Schwartz Gary K GK Chapman Paul B PB Wolchok Jedd D JD Hodi F Stephen FS Carvajal Richard D RD

Cancer 20130802 20

<h4>Background</h4>Uveal melanoma exhibits a high incidence of metastases; and, to date, there is no systemic therapy that clearly improves outcomes. The anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab is a standard of care for metastatic melanoma; however, the clinical activity of CTLA-4 inhibition in patients with metastatic uveal melanoma is poorly defined.<h4>Methods</h4>To assess ipilimumab in this setting, the authors performed a multicenter, retrospective ...[more]

PMID: 23913718

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Project description:BackgroundExtraneural metastasis of glioma is a rare event, often occurring in patients with advanced disease. Genomic alterations associated with extraneural glioma metastasis remain incompletely understood.MethodsTen patients at Memorial Sloan Kettering Cancer Center diagnosed with extraneural metastases of glioblastoma (9 patients) and gliosarcoma (1 patient) from 2003 to 2018 were included in our analysis. Patient characteristics, clinical course, and genomic alterations were evaluated.ResultsPatient age at diagnosis ranged from 14 to 73, with 7 men and 3 women in this group. The median overall survival from initial diagnosis and from diagnosis of extraneural metastasis was 19.6 months (range 11.2 to 57.5 months) and 5 months (range 1 to 16.1 months), respectively. The most common site of extraneural metastasis was bone, with other sites being lymph nodes, dura, liver, lung, and soft tissues. All patients received surgical resection and radiation, and 9 patients received temozolomide, with subsequent chemotherapy appropriate for individual cases. 1 patient had an Ommaya and then ventriculoperitoneal shunt placed, and 1 patient underwent craniectomy for cerebral edema associated with a brain abscess at the initial site of resection. Genomic analysis of primary tumors and metastatic sites revealed shared and private mutations with a preponderance of tumor suppressor gene alterations, illustrating clonal evolution in extraneural metastases.ConclusionsSeveral risk factors emerged for extraneural metastasis of glioblastoma and gliosarcoma, including sarcomatous dedifferentiation, disruption of normal anatomic barriers during surgical resection, and tumor suppressor gene alterations. Next steps with this work include validation of these genomic markers of glioblastoma metastases in larger patient populations and the development of preclinical models. This work will lead to a better understanding of the molecular mechanisms of metastasis to develop targeted treatments for these patients.

Project description:BackgroundThe proliferation of relationships between community health systems and academic medical centers has created a need to identify effective components of these models. This article reports on frontline physician experiences, with one such relationship established through the Memorial Sloan Kettering Cancer Center (MSK) Cancer Alliance. MSK created the Alliance with the goals of rapidly bringing the newest standards of care into community settings and increasing patient access to clinical trials in their local communities.MethodsAlliance leadership administered a 10-question anonymous survey to physicians treating patients with cancer across the 3 Alliance member health systems: Hartford HealthCare Cancer Institute, Lehigh Valley Cancer Institute, and Miami Cancer Institute at Baptist Health South Florida. The purpose of the survey was to identify opportunities to improve physician engagement.ResultsThere were 103 clinician respondents across Alliance members, of which 87 reported participation in a disease management team and were included in the final analysis. Most respondents reported high value from Alliance activities, such as attending MSK tumor boards (94%) and lecture series (96%), among those who reported them applicable. Across all respondents, most reported satisfaction with engagement opportunities, such as MSK physician participation in their institution's meetings (76%). When asked where they would like to see increased engagement, the most commonly reported response was for more lecture series (45%). Most respondents (88%) reported that the Alliance led to practice change, either for themselves or for other clinicians at their institution. Many attributed this practice change to MSK disease-specific process measures.ConclusionsThe activities most valued by community physicians were heavily physician relationship-based. The encouraging experience of the MSK Cancer Alliance suggests that activities involving physician investment may be effective for promoting practice change in the context of cross-institution relationships. Future research is needed in this area.

Dataset Information

Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience.

Publications

Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience.

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