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Melanoma: HELP
Articles by Nikhil H. Ramaiya
Based on 14 articles published since 2009
(Why 14 articles?)
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Between 2009 and 2019, N. Ramaiya wrote the following 14 articles about Melanoma.
 
+ Citations + Abstracts
1 Review Incidence of Programmed Cell Death 1 Inhibitor-Related Pneumonitis in Patients With Advanced Cancer: A Systematic Review and Meta-analysis. 2016

Nishino, Mizuki / Giobbie-Hurder, Anita / Hatabu, Hiroto / Ramaiya, Nikhil H / Hodi, F Stephen. ·Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts. · Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts. · Department of Medical Oncology and Department of Medicine, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts. ·JAMA Oncol · Pubmed #27540850.

ABSTRACT: Importance: Programmed cell death 1 (PD-1) inhibitor-related pneumonitis is a rare but clinically serious and potentially life-threatening adverse event. Little is known about its incidence across different tumor types and treatment regimens. Objective: To compare the incidence of PD-1 inhibitor-related pneumonitis among different tumor types and therapeutic regimens. Data Sources: A PubMed search through November 10, 2015, and a review of references from relevant articles. For the PubMed search, the following keywords or corresponding Medical Subject Heading terms were used: nivolumab, pembrolizumab, and PD-1 inhibitor. Study Selection: Twenty-six original articles of PD-1 inhibitor trial results were identified. Among them, 20 studies of melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC) were eligible for a meta-analysis. Data Extraction and Synthesis: The data were extracted by 1 primary reviewer and then independently reviewed by 2 secondary reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comparisons of the incidence were based on marginal, exact generalized linear models with generalized estimating equations. Main Outcomes and Measures: Incidence of all-grade and grade 3 or higher pneumonitis and pneumonitis-related deaths. Results: Twenty studies of single-tumor-type trials of PD-1 inhibitor (12 melanoma studies, 5 NSCLC studies, and 3 RCC studies) (a total of 4496 unique patients) were included in the meta-analysis. The overall incidence of pneumonitis during PD-1 inhibitor monotherapy was 2.7% (95% CI, 1.9%-3.6%) for all-grade and 0.8% (95% CI, 0.4%-1.2%) for grade 3 or higher pneumonitis. The incidence was higher in NSCLC for all-grade (4.1% vs 1.6%; P = .002) and grade 3 or higher pneumonitis (1.8% vs 0.2%; P < .001) compared with melanoma. The incidence in RCC was higher than in melanoma for all-grade pneumonitis (4.1% vs 1.6%; P < .001) but not for grade 3 or higher pneumonitis. Four pneumonitis-related deaths were observed in patients with NSCLC in the monotherapy group. Pneumonitis was more frequent during combination therapy than monotherapy for all-grade (6.6% vs 1.6%; P < .001) and grade 3 or higher pneumonitis (1.5% vs 0.2%; P = .001) in melanoma, with 1 pneumonitis-related death during combination therapy. Multivariable analyses demonstrated higher odds of pneumonitis in NSCLC for all-grade (odds ratio [OR], 1.43; 95% CI, 1.08-1.89; P = .005) and grade 3 or higher pneumonitis (OR, 2.85; 95% CI, 1.60-5.08; P < .001) and in RCC for all-grade pneumonitis (OR, 1.59; 95% CI, 1.32-1.92; P < .001) compared with melanoma. The combination therapy had significantly higher odds than monotherapy for all-grade (OR, 2.04; 95% CI, 1.69-2.50; P < .001) and grade 3 or higher pneumonitis (OR, 2.86; 95% CI, 1.79- 4.35; P < .001). Conclusions and Relevance: The incidence of PD-1 inhibitor-related pneumonitis was higher in NSCLC and RCC and during combination therapy. These findings contribute to enhance awareness among clinicians and support further investigations to meet the clinical needs.

2 Review Imaging of uncommon esophageal malignancies. 2015

Tirumani, H / Rosenthal, M H / Tirumani, S H / Shinagare, A B / Krajewski, K M / Ramaiya, N H. ·Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. · Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. ·Dis Esophagus · Pubmed #24635682.

ABSTRACT: Malignant esophageal neoplasms other than squamous cell carcinoma and adenocarcinoma are uncommon and include endocrine tumors, lymphoid malignancies, melanoma, malignant stromal tumors, and secondary tumors (metastases). Imaging, though not diagnostic in many cases, helps in selecting the appropriate treatment strategy by determining the anatomic extent of the tumor and locoregional and distant spread. In this article, we provide a comprehensive review of the imaging features of these uncommon esophageal malignancies.

3 Review Personalized tumor response assessment in the era of molecular medicine: cancer-specific and therapy-specific response criteria to complement pitfalls of RECIST. 2012

Nishino, Mizuki / Jagannathan, Jyothi P / Krajewski, Katherine M / O'Regan, Kevin / Hatabu, Hiroto / Shapiro, Geoffrey / Ramaiya, Nikhil H. ·Department of Imaging, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Mizuki_Nishino@dfci.harvard.edu ·AJR Am J Roentgenol · Pubmed #22451534.

ABSTRACT: OBJECTIVE: The purpose of this article is to review cancer- and therapy-specific tumor response assessment criteria used in clinical trials and in practice, with illustrative case examples, and to discuss future directions toward "personalized" tumor response assessment. CONCLUSION: Although Response Evaluation Criteria in Solid Tumors will remain as the primary generalized criteria for response assessment, newer cancer- and therapy-specific criteria will play an important role in providing state-of-the-art response assessment of tumor following molecular targeted therapy and will contribute to personalized cancer care in the era of molecular medicine.

4 Review Radiologic aspects of immune-related tumor response criteria and patterns of immune-related adverse events in patients undergoing ipilimumab therapy. 2011

O'Regan, Kevin N / Jagannathan, Jyothipriya P / Ramaiya, Nikhil / Hodi, F Stephen. ·Department of Radiology, Dana-Farber Cancer Institute and Melanoma Disease Center, Dana-Farber/Brigham and Women's Cancer Center, 44 Binney St, Boston, MA 02115, USA. ·AJR Am J Roentgenol · Pubmed #21785048.

ABSTRACT: OBJECTIVE: The objective of this article is to illustrate examples of radiologic immune-related response criteria and toxicity in patients with advanced melanoma treated with the immunotherapeutic agent ipilimumab. CONCLUSION: Novel immune-related tumor response criteria should be applied to patients undergoing therapy with ipilimumab for advanced melanoma. Ipilimumab also produces a spectrum of immune-related adverse effects that can be recognized radiologically.

5 Clinical Trial PD-1 Inhibitor-Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course. 2016

Nishino, Mizuki / Ramaiya, Nikhil H / Awad, Mark M / Sholl, Lynette M / Maattala, Jennifer A / Taibi, Myriam / Hatabu, Hiroto / Ott, Patrick A / Armand, Philippe F / Hodi, F Stephen. ·Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts. Mizuki_Nishino@dfci.harvard.edu. · Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. · Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts. ·Clin Cancer Res · Pubmed #27535979.

ABSTRACT: PURPOSE: Investigate the clinical characteristics, radiographic patterns, and treatment course of PD-1 inhibitor-related pneumonitis in advanced cancer patients. EXPERIMENTAL DESIGN: Among patients with advanced melanoma, lung cancer, or lymphoma treated in trials of nivolumab, we identified those who developed pneumonitis. Chest CT scans were reviewed to assess extent, distribution, and radiographic patterns of pneumonitis. RESULTS: Among 170 patients treated in 10 different trials of nivolumab, 20 patients (10 melanoma, 6 lymphoma, and 4 lung cancer) developed pneumonitis. Five patients received nivolumab monotherapy, and 15 received combination therapy. The median time from therapy initiation to pneumonitis was 2.6 months. Radiographic pattern was cryptogenic organizing pneumonia (COP) in 13, nonspecific interstitial pneumonia (NSIP) in 3, hypersensitivity pneumonitis (HP) in 2, and acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) in 2 patients. The AIP/ARDS pattern had the highest grade, followed by COP, whereas NSIP and HP had lower grade (median grade: 3, 2, 1, 1, respectively; P = 0.006). The COP pattern was most common in all tumors and treatment regimens. Most patients (17/20; 85%) received corticosteroids, and 3 (15%) also required infliximab. Seven patients restarted nivolumab therapy; 2 of them developed recurrent pneumonitis and were successfully retreated with corticosteroids. One of the patients experienced a pneumonitis flare after completion of corticosteroid taper without nivolumab retreatment. CONCLUSIONS: PD-1 inhibitor-related pneumonitis showed a spectrum of radiographic patterns, reflecting pneumonitis grades. COP was the most common pattern across tumor types and therapeutic regimens. Most patients were successfully treated with corticosteroids. Recurrent pneumonitis and pneumonitis flare were noted in a few patients. Clin Cancer Res; 22(24); 6051-60. ©2016 AACRSee related commentary by Castanon, p. 5956.

6 Clinical Trial Phase 2 study of sunitinib in patients with metastatic mucosal or acral melanoma. 2015

Buchbinder, Elizabeth I / Sosman, Jeffrey A / Lawrence, Donald P / McDermott, David F / Ramaiya, Nikhil H / Van den Abbeele, Annick D / Linette, Gerald P / Giobbie-Hurder, Anita / Hodi, F Stephen. ·Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. · Hematology-Oncology, Vanderbilt University, Nashville, Tennessee. · Hematology-Oncology, Massachusetts General Hospital, Boston, Massachusetts. · Hematology-Oncology, Beth Israel-Deaconess Medical Center, Boston, Massachusetts. · Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. · Department of Imaging, Dana-Farber Cancer Institute, Boston, Massachusetts. · Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts. · Hematology-Oncology, Washington University in St. Louis, St. Louis, Missouri. · Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts. ·Cancer · Pubmed #26264378.

ABSTRACT: BACKGROUND: Patients with mucosal and acral melanomas have limited treatment options and a poor prognosis. Mutations of the KIT oncogene in these melanoma subtypes provide a potential therapeutic target. METHODS: A multicenter phase 2 trial of sunitinib was conducted in patients with unresectable stage III or IV melanoma of a mucosal or acral primary origin. Patients were treated in 2 cohorts: cohort A received sunitinib at a dose of 50 mg daily for 4 weeks of a 6-week cycle, and cohort B received sunitinib at a dose of 37.5 mg daily on a continuous basis. Dose reductions were permitted for treatment-related toxicities, and tumor assessments were performed every 2 months. RESULTS: Fifty-two patients were enrolled: 21 in cohort A and 31 in cohort B. Four patients had confirmed partial responses, which lasted 5 to 10 months (1 with a KIT mutation). In both cohorts, the proportion of patients alive and progression-free at 2 months was 52% (95% confidence interval, 38%-66%); this was significantly larger than the hypothesized null of 5%. There was no significant difference in response or overall survival between the 25% of patients with a KIT mutation and those without one (response rate, 7.7% vs 9.7%; overall survival, 6.4 vs 8.6 months). The overall disease control rate was 44%, and a high rate of toxicity was associated with the treatment. CONCLUSIONS: Sunitinib showed activity in the treatment of mucosal and acral melanoma that was not dependent on the presence of a KIT mutation. However, the medication was poorly tolerated, and there were no prolonged responses. Cancer 2015;121:4007-4015. © 2015 American Cancer Society.

7 Clinical Trial Phase II Study of Nilotinib in Melanoma Harboring KIT Alterations Following Progression to Prior KIT Inhibition. 2015

Carvajal, Richard D / Lawrence, Donald P / Weber, Jeffrey S / Gajewski, Thomas F / Gonzalez, Rene / Lutzky, Jose / O'Day, Steven J / Hamid, Omid / Wolchok, Jedd D / Chapman, Paul B / Sullivan, Ryan J / Teitcher, Jerrold B / Ramaiya, Nikhil / Giobbie-Hurder, Anita / Antonescu, Cristina R / Heinrich, Michael C / Bastian, Boris C / Corless, Christopher L / Fletcher, Jonathan A / Hodi, F Stephen. ·Memorial Sloan Kettering Cancer Center, New York, New York. Weill Medical College of Cornell University, New York, New York. · Massachusetts General Hospital, Boston, Massachusetts. · H. Lee Moffitt Cancer Center, Tampa, Florida. · The University of Chicago, Chicago, Illinois. · The University of Colorado Cancer Center, Aurora, Colorado. · Mount Sinai Comprehensive Cancer Center, Miami Beach, Florida. · Beverly Hills Cancer Center, Beverly Hills, California. · Angeles Clinic and Research Institute, Los Angeles, California. · Memorial Sloan Kettering Cancer Center, New York, New York. · Dana Farber Cancer Institute, Boston, Massachusetts. · Oregon Health and Science University, Portland, Oregon. · The University of California San Francisco, San Francisco, California. · Dana Farber Cancer Institute, Boston, Massachusetts. Stephen_hodi@dfci.harvard.edu. ·Clin Cancer Res · Pubmed #25695690.

ABSTRACT: PURPOSE: Although durable responses can be achieved with tyrosine kinase inhibitors such as imatinib in melanomas harboring KIT mutations, the efficacy of alternative inhibitors after progression to imatinib and the activity of these agents on brain metastases are unknown. EXPERIMENTAL DESIGN: We conducted a phase II study of nilotinib 400 mg twice a day in two cohorts of patients with melanomas harboring KIT mutations or amplification: (A) those refractory or intolerant to a prior KIT inhibitor; and (B) those with brain metastases. The primary endpoint was 4-month disease control rate. Secondary endpoints included response rate, time-to-progression (TTP), and overall survival (OS). A Simon two-stage and a single-stage design was planned to assess for the primary endpoint in cohorts A and B, respectively. RESULTS: Twenty patients were enrolled and 19 treated (11 in cohort A; 8 in cohort B). Three patients on cohort A [27%; 95% confidence interval (CI), 8%-56%] and 1 on cohort B (12.5%; 90% CI, 0.6%-47%) achieved the primary endpoint. Two partial responses were observed in cohort A (18.2%; 90% CI, 3%-47%); none were observed in cohort B. The median TTP and OS was 3.3 (90% CI, 2.1-3.9 months) and 9.1 months (90% CI, 4.3-14.2 months), respectively, in all treated patients. CONCLUSIONS: Nilotinib may achieve disease control in patients with melanoma harboring KIT alterations and whose disease progressed after imatinib therapy. The efficacy of this agent in KIT-altered melanoma with brain metastasis is limited.

8 Clinical Trial Bevacizumab plus ipilimumab in patients with metastatic melanoma. 2014

Hodi, F Stephen / Lawrence, Donald / Lezcano, Cecilia / Wu, Xinqi / Zhou, Jun / Sasada, Tetsuro / Zeng, Wanyong / Giobbie-Hurder, Anita / Atkins, Michael B / Ibrahim, Nageatte / Friedlander, Philip / Flaherty, Keith T / Murphy, George F / Rodig, Scott / Velazquez, Elsa F / Mihm, Martin C / Russell, Sara / DiPiro, Pamela J / Yap, Jeffrey T / Ramaiya, Nikhil / Van den Abbeele, Annick D / Gargano, Maria / McDermott, David. ·Authors' Affiliations: Departments of Medical Oncology, Stephen_Hodi@dfci.harvard.edu. · Massachusetts General Hospital Cancer Center; Departments of. · University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; · Authors' Affiliations: Departments of Medical Oncology. · Biostatistics, and. · Lombardi Cancer Center Georgetown University, Washington, District of Columbia; and. · Mount Sinai Medical Center, New York, New York. · Pathology and. · Tufts University; Miraca Life Sciences, Newton, Massachusetts; · Surgery, Brigham and Women's Hospital; · Imaging, Dana-Farber Cancer Institute; · Beth Israel-Deaconess Medical Center, Boston; ·Cancer Immunol Res · Pubmed #24838938.

ABSTRACT: Ipilimumab improves survival in advanced melanoma and can induce immune-mediated tumor vasculopathy. Besides promoting angiogenesis, vascular endothelial growth factor (VEGF) suppresses dendritic cell maturation and modulates lymphocyte endothelial trafficking. This study investigated the combination of CTLA4 blockade with ipilimumab and VEGF inhibition with bevacizumab. Patients with metastatic melanoma were treated in four dosing cohorts of ipilimumab (3 or 10 mg/kg) with four doses at 3-week intervals and then every 12 weeks, and bevacizumab (7.5 or 15 mg/kg) every 3 weeks. Forty-six patients were treated. Inflammatory events included giant cell arteritis (n = 1), hepatitis (n = 2), and uveitis (n = 2). On-treatment tumor biopsies revealed activated vessel endothelium with extensive CD8(+) and macrophage cell infiltration. Peripheral blood analyses demonstrated increases in CCR7(+/-)/CD45RO(+) cells and anti-galectin antibodies. Best overall response included 8 partial responses, 22 instances of stable disease, and a disease-control rate of 67.4%. Median survival was 25.1 months. Bevacizumab influences changes in tumor vasculature and immune responses with ipilimumab administration. The combination of bevacizumab and ipilimumab can be safely administered and reveals VEGF-A blockade influences on inflammation, lymphocyte trafficking, and immune regulation. These findings provide a basis for further investigating the dual roles of angiogenic factors in blood vessel formation and immune regulation, as well as future combinations of antiangiogenesis agents and immune checkpoint blockade.

9 Article Immune-Related Tumor Response Dynamics in Melanoma Patients Treated with Pembrolizumab: Identifying Markers for Clinical Outcome and Treatment Decisions. 2017

Nishino, Mizuki / Giobbie-Hurder, Anita / Manos, Michael P / Bailey, Nancy / Buchbinder, Elizabeth I / Ott, Patrick A / Ramaiya, Nikhil H / Hodi, F Stephen. ·Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts. Mizuki_Nishino@dfci.harvard.edu. · Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts. · Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts. · Department of Medicine, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts. · Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts. ·Clin Cancer Res · Pubmed #28592629.

ABSTRACT:

10 Article Radiographic Profiling of Immune-Related Adverse Events in Advanced Melanoma Patients Treated with Ipilimumab. 2015

Tirumani, Sree Harsha / Ramaiya, Nikhil H / Keraliya, Abhishek / Bailey, Nancy D / Ott, Patrick A / Hodi, F Stephen / Nishino, Mizuki. ·Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts. · Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts. Mizuki_Nishino@dfci.harvard.edu. ·Cancer Immunol Res · Pubmed #26100356.

ABSTRACT: Ipilimumab is a promising novel immunotherapy agent and is associated with a variety of immune-related adverse events (irAE). The purpose of this study was to investigate the manifestations of irAEs on body imaging in patients with advanced melanoma treated with ipilimumab. One-hundred forty-seven patients with advanced melanoma (59 women, 88 men; median age, 64.5 years) treated with ipilimumab were studied. All patients had the baseline and at least one follow-up chest/abdomen/pelvis CT or PET/CT during therapy, which were reviewed by a consensus of two radiologists blinded to the clinical data. Findings indicative of individual types of irAEs were assessed, including thyroiditis, sarcoid-like lymphadenopathy, pneumonitis, hepatitis, pancreatitis, and colitis. Among the 147 patients, 46 (31%) had radiologically identified irAEs. The time interval from the initiation of therapy to the development of irAEs was less than 3 months in 76% (35 of 46) of the patients (range, 0.2-9.1 months). Clinical characteristics did not differ between patients with and without irAEs (P > 0.18). Among the individual types of irAEs, colitis was most common (n = 28; 19%), followed by sarcoid-like lymphadenopathy (n = 8; 5%) and pneumonitis (n = 8; 5%). Hepatitis (n = 3), thyroiditis (n = 2), and pancreatitis (n = 1) were less common. The resolution of irAEs was noted in 32 of 36 patients (89%) with further follow-up scans, with a median time of 2.3 months after the detection of irAE. In conclusion, irAEs were noted on body imaging in 31% of patients with melanoma treated with ipilimumab. Colitis was the most common, followed by sarcoid-like lymphadenopathy and pneumonitis. The results call for an increased awareness of irAEs, given the expanding role of cancer immunotherapy.

11 Article Metastatic mucosal melanoma: imaging patterns of metastasis and recurrence. 2013

O'Regan, Kevin / Breen, Micheál / Ramaiya, Nikhil / Jagannathan, Jyothi / DiPiro, Pamela J / Hodi, F Stephen / Van den Abbeele, Annick D. ·Department of Radiology, Cork University Hospital, Wilton, Cork, Ireland. · Department of Imaging. · Department of Cutaneous Oncology Program, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA. ·Cancer Imaging · Pubmed #24434078.

ABSTRACT: PURPOSE: Mucosal melanoma is a rare but aggressive subtype of melanoma with unique clinicopathologic features. We hypothesize that mucosal melanoma shows predilection for separate and unique metastatic pathways. MATERIALS AND METHODS: This was a retrospective analysis of 19 patients (5 men and 14 women; median age 60 years, range 38-76 years) with metastatic mucosal melanoma presenting to a tertiary oncology center between 2005 and 2010. We performed a review of medical records and histologic and imaging studies to evaluate the natural history, metastatic patterns and the role of imaging in the management of patients with advanced mucosal melanoma. RESULTS: At presentation, disease was confined to the primary site (58%, n = 11) or to the regional lymph nodes (32%, n = 6) in most patients. The most common site of metastasis was the lungs (89%, n = 16), followed by the liver (67%, n = 12) and peritoneum (44%, n = 8). Sinonasal melanoma preferentially spread to the liver (100%, n = 4), vaginal melanoma to the lungs (100%, n = 7) and anal melanoma to the inguinal lymph nodes (100%, n = 4). CONCLUSION: Pathways of metastatic spread in mucosal melanoma may differ from other forms of melanoma and between different primary sites of mucosal origin.

12 Article 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. 2013

Luke, Jason J / Callahan, Margaret K / Postow, Michael A / Romano, Emanuela / Ramaiya, Nikhil / Bluth, Mark / Giobbie-Hurder, Anita / Lawrence, Donald P / Ibrahim, Nageatte / Ott, Patrick A / Flaherty, Keith T / Sullivan, Ryan J / Harding, James J / D'Angelo, Sandra / Dickson, Mark / Schwartz, Gary K / Chapman, Paul B / Wolchok, Jedd D / Hodi, F Stephen / Carvajal, Richard D. ·Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. ·Cancer · Pubmed #23913718.

ABSTRACT: BACKGROUND: 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. METHODS: 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. RESULTS: 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/μL at week 7 were associated significantly with survival. CONCLUSIONS: 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.

13 Article Developing a common language for tumor response to immunotherapy: immune-related response criteria using unidimensional measurements. 2013

Nishino, Mizuki / Giobbie-Hurder, Anita / Gargano, Maria / Suda, Margaret / Ramaiya, Nikhil H / Hodi, F Stephen. ·Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, USA. Mizuki_Nishino@dfci.harvard.edu ·Clin Cancer Res · Pubmed #23743568.

ABSTRACT: PURPOSE: Immune-related response criteria (irRC) was developed to adequately assess tumor response to immunotherapy. The irRC are based on bidimensional measurements, as opposed to unidimensional measurements defined by Response Evaluation Criteria in Solid Tumors, which has been widely used in solid tumors. We aimed to compare response assessment by bidimensional versus unidimensional irRC in patients with advanced melanoma treated with ipilimumab. EXPERIMENTAL DESIGN: Fifty-seven patients with advanced melanoma treated with ipilimumab in a phase II, expanded access trial were studied. Bidimensional tumor measurement records prospectively conducted during the trial were reviewed to generate a second set of measurements using unidimensional, longest diameter measurements. The percent changes of measurements at follow-up, best overall response, and time-to-progression (TTP) were compared between bidimensional and unidimensional irRC. Interobserver variability for bidimensional and unidimensional measurements was assessed in 25 randomly selected patients. RESULTS: The percent changes at follow-up scans were highly concordant between the 2 criteria (Spearman r: 0.953-0.965, first to fourth follow-up). The best immune-related response was highly concordant between the 2 criteria (κw = 0.881). TTP was similar between the bidimensional and unidimensional assessments (progression-free at 6 months: 70% vs. 81%, respectively). The unidimensional measurements were more reproducible than bidimensional measurements, with the 95% limits of agreement of (-16.1%, 5.8%) versus (-31.3%, 19.7%), respectively. CONCLUSION: irRC using the unidimensional measurements provided highly concordant response assessment compared with the bidimensional irRC, with less measurement variability. The use of unidimensional irRC is proposed to assess response to immunotherapy in solid tumors, given its simplicity, higher reproducibility, and high concordance with the bidimensional irRC.

14 Article Ipilimumab for patients with advanced mucosal melanoma. 2013

Postow, Michael A / Luke, Jason J / Bluth, Mark J / Ramaiya, Nikhil / Panageas, Katherine S / Lawrence, Donald P / Ibrahim, Nageatte / Flaherty, Keith T / Sullivan, Ryan J / Ott, Patrick A / Callahan, Margaret K / Harding, James J / D'Angelo, Sandra P / Dickson, Mark A / Schwartz, Gary K / Chapman, Paul B / Gnjatic, Sacha / Wolchok, Jedd D / Hodi, F Stephen / Carvajal, Richard D. ·Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. carvajar@mskcc.org ·Oncologist · Pubmed #23716015.

ABSTRACT: The outcome of patients with mucosal melanoma treated with ipilimumab is not defined. To assess the efficacy and safety of ipilimumab in this melanoma subset, we performed a multicenter, retrospective analysis of 33 patients with unresectable or metastatic mucosal melanoma treated with ipilimumab. The clinical characteristics, treatments, toxicities, radiographic assessment of disease burden by central radiology review at each site, and mutational profiles of the patients' tumors were recorded. Available peripheral blood samples were used to assess humoral immunity against a panel of cancer-testis antigens and other antigens. By the immune-related response criteria of the 30 patients who underwent radiographic assessment after ipilimumab at approximately week 12, there were 1 immune-related complete response, 1 immune-related partial response, 6 immune-related stable disease, and 22 immune-related progressive disease. By the modified World Health Organization criteria, there were 1 immune-related complete response, 1 immune-related partial response, 5 immune-related stable disease, and 23 immune-related progressive disease. Immune-related adverse events (as graded by Common Terminology Criteria for Adverse Events version 4.0) consisted of six patients with rash (four grade 1, two grade 2), three patients with diarrhea (one grade 1, two grade 3), one patient with grade 1 thyroiditis, one patient with grade 3 hepatitis, and 1 patient with grade 2 hypophysitis. The median overall survival from the time of the first dose of ipilimumab was 6.4 months (range: 1.8-26.7 months). Several patients demonstrated serologic responses to cancer-testis antigens and other antigens. Durable responses to ipilimumab were observed, but the overall response rate was low. Additional investigation is necessary to clarify the role of ipilimumab in patients with mucosal melanoma.