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Melanoma: HELP
Articles by Nikhil I. Khushalani
Based on 14 articles published since 2008
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Between 2008 and 2019, N. I. Khushalani wrote the following 14 articles about Melanoma.
 
+ Citations + Abstracts
1 Guideline Melanoma, version 4.2014. 2014

Coit, Daniel G / Thompson, John A / Andtbacka, Robert / Anker, Christopher J / Bichakjian, Christopher K / Carson, William E / Daniels, Gregory A / Daud, Adil / Dimaio, Dominick / Fleming, Martin D / Gonzalez, Rene / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Kelley, Mark C / Khushalani, Nikhil I / Kudchadkar, Ragini R / Lange, Julie R / Martini, Mary C / Olszanski, Anthony J / Ross, Merrick I / Salama, April / Swetter, Susan M / Tanabe, Kenneth K / Trisal, Vijay / Urist, Marshall M / McMillian, Nicole R / Ho, Maria / Anonymous5170793. ·From 1Memorial Sloan-Kettering Cancer Center; 2Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance; 3Huntsman Cancer Institute at the University of Utah; 4University of Michigan Comprehensive Cancer Center; 5The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; 6UC San Diego Moores Cancer Center; 7UCSF Helen Diller Family Comprehensive Cancer Center; 8Fred & Pamela Buffett Cancer Center at The Nebraska Medical Center; 9St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; 10University of Colorado Cancer Center; 11Aim at Melanoma; 12Dana-Farber/Brigham and Women's Cancer Center; 13Vanderbilt-Ingram Cancer Center; 14Roswell Park Cancer Institute; 15Moffitt Cancer Center; 16The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 17Robert H. Lurie Comprehensive Cancer Center of Northwestern University; 18Fox Chase Cancer Center; 19The University of Texas MD Anderson Cancer Center; 20Duke Cancer Institute; 21Stanford Cancer Institute; 22Massachusetts General Hospital Cancer Center; 23City of Hope Comprehensive Cancer Center; 24University of Alabama at Birmingham Comprehensive Cancer Center; and 25National Comprehensive Cancer Network. ·J Natl Compr Canc Netw · Pubmed #24812131.

ABSTRACT: The NCCN Guidelines for Melanoma provide multidisciplinary recommendations for the management of patients with melanoma. These NCCN Guidelines Insights highlight notable recent updates. Dabrafenib and trametinib, either as monotherapy (category 1) or combination therapy, have been added as systemic options for patients with unresectable metastatic melanoma harboring BRAF V600 mutations. Controversy continues regarding the value of adjuvant radiation for patients at high risk of nodal relapse. This is reflected in the category 2B designation to consider adjuvant radiation following lymphadenectomy for stage III melanoma with clinically positive nodes or recurrent disease.

2 Guideline Melanoma, version 2.2013: featured updates to the NCCN guidelines. 2013

Coit, Daniel G / Andtbacka, Robert / Anker, Christopher J / Bichakjian, Christopher K / Carson, William E / Daud, Adil / Dimaio, Dominick / Fleming, Martin D / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Kelley, Mark C / Khushalani, Nikhil I / Kudchadkar, Ragini R / Lange, Julie R / Lind, Anne / Martini, Mary C / Olszanski, Anthony J / Pruitt, Scott K / Ross, Merrick I / Swetter, Susan M / Tanabe, Kenneth K / Thompson, John A / Trisal, Vijay / Urist, Marshall M / McMillian, Nicole / Ho, Maria / Anonymous4310755. ·Memorial Sloan-Kettering Cancer Center. ·J Natl Compr Canc Netw · Pubmed #23584343.

ABSTRACT: The NCCN Guidelines for Melanoma provide multidisciplinary recommendations on the clinical management of patients with melanoma. This NCCN Guidelines Insights report highlights notable recent updates. Foremost of these is the exciting addition of the novel agents ipilimumab and vemurafenib for treatment of advanced melanoma. The NCCN panel also included imatinib as a treatment for KIT-mutated tumors and pegylated interferon alfa-2b as an option for adjuvant therapy. Also important are revisions to the initial stratification of early-stage lesions based on the risk of sentinel lymph node metastases, and revised recommendations on the use of sentinel lymph node biopsy for low-risk groups. Finally, the NCCN panel reached clinical consensus on clarifying the role of imaging in the workup of patients with melanoma.

3 Guideline Melanoma. 2012

Coit, Daniel G / Andtbacka, Robert / Anker, Christopher J / Bichakjian, Christopher K / Carson, William E / Daud, Adil / Dilawari, Raza A / Dimaio, Dominick / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Kelley, Mark C / Khushalani, Nikhil I / Kudchadkar, Ragini R / Lange, Julie R / Lind, Anne / Martini, Mary C / Olszanski, Anthony J / Pruitt, Scott K / Ross, Merrick I / Swetter, Susan M / Tanabe, Kenneth K / Thompson, John A / Trisal, Vijay / Urist, Marshall M / Anonymous590720. · ·J Natl Compr Canc Netw · Pubmed #22393197.

ABSTRACT: -- No abstract --

4 Review Intralesional and systemic immunotherapy for metastatic melanoma. 2016

Luu, Carrie / Khushalani, Nikhil I / Zager, Jonathan S. ·a Department of Cutaneous Oncology , H. Lee Moffitt Cancer Center , Tampa , FL , USA. · b Department of Cutaneous Oncology , Director of Regional Therapies Moffitt Cancer Center , Tampa , FL , USA. ·Expert Opin Biol Ther · Pubmed #27602429.

ABSTRACT: INTRODUCTION: Immunotherapy has revolutionized the treatment of metastatic melanoma and dramatically improved patient outcomes. Ipilimumab, an inhibitor of cytotoxic T-lymphocyte antigen-4 (CTLA-4), was the first immunotherapeutic agent to demonstrate improved survival in advanced melanoma. More recently, other immune checkpoint inhibitors, including the programmed death-1 (PD-1) inhibitors pembrolizumab and nivolumab, have demonstrated efficacy in locally advanced unresectable and metastatic melanoma. In addition to systemically delivered immunotherapies, intralesional therapies such as talimogene laherparepvec (TVEC) play an important role in the treatment of locoregionally advanced and metastatic melanoma. Areas covered: This review provides an overview of the mechanisms behind immune checkpoint inhibitors. Clinical evidence of their efficacy is presented and discussion of new patterns of response and associated immune related adverse events associated with immunotherapy are provided. Expert opinion: Treatment options for locally advanced and metastatic melanoma are expanding with new developments in immunotherapy and immune checkpoint inhibitors. The utility of these novel therapies in the adjuvant setting is currently being explored. The ideal treatment of metastatic melanoma continues to be multimodal, combining systemic treatments, intralesional and regional therapies, surgery and radiotherapy to achieve optimal outcomes.

5 Clinical Trial Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. 2018

Tawbi, Hussein A / Forsyth, Peter A / Algazi, Alain / Hamid, Omid / Hodi, F Stephen / Moschos, Stergios J / Khushalani, Nikhil I / Lewis, Karl / Lao, Christopher D / Postow, Michael A / Atkins, Michael B / Ernstoff, Marc S / Reardon, David A / Puzanov, Igor / Kudchadkar, Ragini R / Thomas, Reena P / Tarhini, Ahmad / Pavlick, Anna C / Jiang, Joel / Avila, Alexandre / Demelo, Sheena / Margolin, Kim. ·From the University of Texas M.D. Anderson Cancer Center, Houston (H.A.T.) · Moffitt Cancer Center and Research Institute, Tampa, FL (P.A.F., N.I.K.) · University of California-San Francisco, San Francisco (A. Algazi), the Angeles Clinic and Research Institute, Los Angeles (O.H.), Stanford University Hospital, Palo Alto (R.P.T.), and the Department of Medical Oncology, City of Hope, Duarte (K.M.) - all in California · Dana-Farber Cancer Institute, Boston (F.S.H., D.A.R.) · University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (S.J.M.) · University of Colorado Comprehensive Cancer Center, Aurora (K.L.) · University of Michigan, Ann Arbor (C.D.L.) · Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (M.A.P.), Roswell Park Cancer Institute, Buffalo (M.S.E., I.P.), and New York University, Lake Success (A.C.P.) - all in New York · Georgetown-Lombardi Comprehensive Cancer Center, Washington DC (M.B.A.) · Winship Cancer Institute of Emory University, Atlanta (R.R.K.) · University of Pittsburgh Medical Center, Pittsburgh (A.T.) · Bristol-Myers Squibb, Princeton, NJ (J.J., A. Avila, S.D.) · and Cleveland Clinic-Taussig Cancer Institute, Cleveland (A.T.). ·N Engl J Med · Pubmed #30134131.

ABSTRACT: BACKGROUND: Brain metastases are a common cause of disabling neurologic complications and death in patients with metastatic melanoma. Previous studies of nivolumab combined with ipilimumab in metastatic melanoma have excluded patients with untreated brain metastases. We evaluated the efficacy and safety of nivolumab plus ipilimumab in patients with melanoma who had untreated brain metastases. METHODS: In this open-label, multicenter, phase 2 study, patients with metastatic melanoma and at least one measurable, nonirradiated brain metastasis (tumor diameter, 0.5 to 3 cm) and no neurologic symptoms received nivolumab (1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for up to four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks until progression or unacceptable toxic effects. The primary end point was the rate of intracranial clinical benefit, defined as the percentage of patients who had stable disease for at least 6 months, complete response, or partial response. RESULTS: Among 94 patients with a median follow-up of 14.0 months, the rate of intracranial clinical benefit was 57% (95% confidence interval [CI], 47 to 68); the rate of complete response was 26%, the rate of partial response was 30%, and the rate of stable disease for at least 6 months was 2%. The rate of extracranial clinical benefit was 56% (95% CI, 46 to 67). Treatment-related grade 3 or 4 adverse events were reported in 55% of patients, including events involving the central nervous system in 7%. One patient died from immune-related myocarditis. The safety profile of the regimen was similar to that reported in patients with melanoma who do not have brain metastases. CONCLUSIONS: Nivolumab combined with ipilimumab had clinically meaningful intracranial efficacy, concordant with extracranial activity, in patients with melanoma who had untreated brain metastases. (Funded by Bristol-Myers Squibb and the National Cancer Institute; CheckMate 204 ClinicalTrials.gov number, NCT02320058 .).

6 Clinical Trial Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma. 2017

Zimmer, Lisa / Apuri, Susmitha / Eroglu, Zeynep / Kottschade, Lisa A / Forschner, Andrea / Gutzmer, Ralf / Schlaak, Max / Heinzerling, Lucie / Krackhardt, Angela M / Loquai, Carmen / Markovic, Svetomir N / Joseph, Richard W / Markey, Kelly / Utikal, Jochen S / Weishaupt, Carsten / Goldinger, Simone M / Sondak, Vernon K / Zager, Jonathan S / Schadendorf, Dirk / Khushalani, Nikhil I. ·Department of Dermatology, University Hospital, University Duisburg-Essen, Germany & German Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address: lisa.zimmer@uk-essen.de. · Hematology/Oncology Fellowship Program, H Lee Moffitt Cancer Center and Research Institute/University of South Florida, Tampa, FL, USA. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA. · Department of Oncology, Hematology and Immunology, Mayo Clinic, Rochester, MN, USA. · Department of Dermatology, University Hospital Tübingen, Germany. · Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Germany. · Department of Dermatology, University Hospital Cologne, Skin Cancer Center, Center for Integrated Oncology (CIO) Köln Bonn, Germany. · Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany. · III. Medical Department, Technische Universität München (TUM) Munich, Germany. · Department of Dermatology, University Hospital Mainz, Germany. · Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany. · Department of Dermatology, University Hospital Münster, Germany. · Department of Dermatology, University Hospital Zurich, Switzerland. · Department of Dermatology, University Hospital, University Duisburg-Essen, Germany & German Cancer Consortium (DKTK), Heidelberg, Germany. ·Eur J Cancer · Pubmed #28214657.

ABSTRACT: BACKGROUND: The anti-programmed cell death-1 (PD-1) inhibitors pembrolizumab and nivolumab alone or in combination with ipilimumab have shown improved objective response rates and progression-free survival compared to ipilimumab only in advanced melanoma patients. Anti-PD-1 therapy demonstrated nearly equal clinical efficacy in patients who had progressed after ipilimumab or were treatment-naïve. However, only limited evidence exists regarding the efficacy of ipilimumab alone or in combination with nivolumab after treatment failure to anti-PD-therapy. PATIENTS AND METHODS: A multicenter retrospective study in advanced melanoma patients who were treated with nivolumab (1 or 3 mg/kg) and ipilimumab (1 mg or 3 mg/kg) or ipilimumab (3 mg/kg) alone after treatment failure to anti-PD-1 therapy was performed. Patient, tumour, pre- and post-treatment characteristics were analysed. RESULTS: In total, 47 patients were treated with ipilimumab (ipi-group) and 37 patients with ipilimumab and nivolumab (combination-group) after treatment failure to anti-PD-1 therapy. Overall response rates for the ipi- and the combination-group were 16% and 21%, respectively. Disease control rate was 42% for the ipi-group and 33% for the combination-group. One-year overall survival rates for the ipi- and the combination-group were 54% and 55%, respectively. CONCLUSIONS: Ipilimumab should be considered as a viable treatment option for patients with failure to prior anti-PD-1 therapy, including those with progressive disease as best response to prior anti-PD-1. In contrast, the combination of ipilimumab and nivolumab appears significantly less effective in this setting compared to treatment-naïve patients.

7 Clinical Trial Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. 2015

Weber, Jeffrey S / D'Angelo, Sandra P / Minor, David / Hodi, F Stephen / Gutzmer, Ralf / Neyns, Bart / Hoeller, Christoph / Khushalani, Nikhil I / Miller, Wilson H / Lao, Christopher D / Linette, Gerald P / Thomas, Luc / Lorigan, Paul / Grossmann, Kenneth F / Hassel, Jessica C / Maio, Michele / Sznol, Mario / Ascierto, Paolo A / Mohr, Peter / Chmielowski, Bartosz / Bryce, Alan / Svane, Inge M / Grob, Jean-Jacques / Krackhardt, Angela M / Horak, Christine / Lambert, Alexandre / Yang, Arvin S / Larkin, James. ·Moffitt Cancer Center, Tampa, FL, USA. Electronic address: jeffrey.weber@moffitt.org. · Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. · California Pacific Center for Melanoma Research, San Francisco, CA, USA. · Dana-Farber Cancer Institute, Boston, MA, USA. · Medizinische Hochschule Hannover, Hannover, Germany. · Universitair Ziekenhuis Brussel, Brussels, Belgium. · Medical University of Vienna, Vienna, Austria. · Roswell Park Cancer Institute, Buffalo, NY, USA. · Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, QC, Canada. · University of Michigan, Ann Arbor, MI, USA. · Washington University, St Louis, MO, USA. · Centre Hospitalier Universitaire de Lyon, Lyon, France. · Christie Hospital, Manchester, UK. · Huntsman Cancer Institute, Salt Lake City, UT, USA. · German Cancer Research Centre University Hospital, Heidelberg, Germany. · Medical Oncology and Immunotherapy, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy. · Yale Cancer Center, New Haven, CT, USA. · Istituto Nazionale Tumori Fondazione G Pascale, Naples, Italy. · Elbe Kliniken Buxtehude, Buxtehude, Germany. · Department of Medicine, University of California, Los Angeles, CA, USA. · Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA. · Department of Oncology, Herlev Hospital, Copenhagen, Denmark. · Aix-Marseille University, Hopital de la Timone, Marseille, France. · Technische Universität München School of Medicine, II Medical Department, Munich, Germany. · Bristol-Myers Squibb, Princeton, NJ, USA. · Bristol-Myers Squibb, Braine-I'Alleud, Belgium. · Royal Marsden Hospital, London, UK. ·Lancet Oncol · Pubmed #25795410.

ABSTRACT: BACKGROUND: Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors. We assessed the efficacy and safety of nivolumab compared with investigator's choice of chemotherapy (ICC) as a second-line or later-line treatment in patients with advanced melanoma. METHODS: In this randomised, controlled, open-label, phase 3 trial, we recruited patients at 90 sites in 14 countries. Eligible patients were 18 years or older, had unresectable or metastatic melanoma, and progressed after ipilimumab, or ipilimumab and a BRAF inhibitor if they were BRAF(V 600) mutation-positive. Participating investigators randomly assigned (with an interactive voice response system) patients 2:1 to receive an intravenous infusion of nivolumab 3 mg/kg every 2 weeks or ICC (dacarbazine 1000 mg/m(2) every 3 weeks or paclitaxel 175 mg/m(2) combined with carboplatin area under the curve 6 every 3 weeks) until progression or unacceptable toxic effects. We stratified randomisation by BRAF mutation status, tumour expression of PD-L1, and previous best overall response to ipilimumab. We used permuted blocks (block size of six) within each stratum. Primary endpoints were the proportion of patients who had an objective response and overall survival. Treatment was given open-label, but those doing tumour assessments were masked to treatment assignment. We assessed objective responses per-protocol after 120 patients had been treated with nivolumab and had a minimum follow-up of 24 weeks, and safety in all patients who had had at least one dose of treatment. The trial is closed and this is the first interim analysis, reporting the objective response primary endpoint. This study is registered with ClinicalTrials.gov, number NCT01721746. FINDINGS: Between Dec 21, 2012, and Jan 10, 2014, we screened 631 patients, randomly allocating 272 patients to nivolumab and 133 to ICC. Confirmed objective responses were reported in 38 (31·7%, 95% CI 23·5-40·8) of the first 120 patients in the nivolumab group versus five (10·6%, 3·5-23·1) of 47 patients in the ICC group. Grade 3-4 adverse events related to nivolumab included increased lipase (three [1%] of 268 patients), increased alanine aminotransferase, anaemia, and fatigue (two [1%] each); for ICC, these included neutropenia (14 [14%] of 102), thrombocytopenia (six [6%]), and anaemia (five [5%]). We noted grade 3-4 drug-related serious adverse events in 12 (5%) nivolumab-treated patients and nine (9%) patients in the ICC group. No treatment-related deaths occurred. INTERPRETATION: Nivolumab led to a greater proportion of patients achieving an objective response and fewer toxic effects than with alternative available chemotherapy regimens for patients with advanced melanoma that has progressed after ipilimumab or ipilimumab and a BRAF inhibitor. Nivolumab represents a new treatment option with clinically meaningful durable objective responses in a population of high unmet need. FUNDING: Bristol-Myers Squibb.

8 Article Management of intussusception in patients with melanoma. 2019

Perez, Matthew C / Sun, James / Farley, Clara / Han, Dale / Sun, Alexander H / Narayan, Deepak / Lowe, Michael / Delman, Keith A / Messina, Jane L / Gonzalez, Ricardo J / Sondak, Vernon K / Khushalani, Nikhil I / Zager, Jonathan S. ·Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida. · Division of Surgical Oncology, Emory University, Atlanta, Georgia. · Division of Surgical Oncology, Department of Surgery, Oregon Health and Science University, Portland, Oregon. · Department of Plastic and Reconstructive Surgery, Johns Hopkins University, Baltimore, Maryland. · Division of Plastic Surgery, Department of Surgery, Yale University, New Haven, Connecticut. ·J Surg Oncol · Pubmed #30734297.

ABSTRACT: BACKGROUND: Increased cross-sectional imaging for surveillance of metastatic melanoma has led to more diagnoses of asymptomatic intussusception. METHODS: We performed a multi-institutional retrospective review of patient records with a history of metastatic melanoma and a diagnosis of intussusception. Patients were divided into three groups: 1) asymptomatic patients without current evidence of melanoma (no evidence of disease [NED]); 2) asymptomatic intussusception and known active metastatic melanoma; 3) symptomatic intussusception and known active metastatic melanoma; the number of patients requiring surgery and intraoperative findings were recorded. RESULTS: We reviewed 73 patients diagnosed with intussusception from 2004 to 2017. Among asymptomatic patients with NED (n = 16), 14 spontaneously resolved and 2 underwent pre-emptive surgery without abnormal intraoperative findings. Of asymptomatic patients with active metastatic disease (n = 32), 25 were initially observed and 7 underwent pre-emptive surgery and 9 of the 25 initially observed patients required surgery for development of symptoms. In this group, all 16 patients undergoing surgery (50% of the group) had intraoperative findings of intussusception and/or metastatic intestinal melanoma.. All symptomatic patients with metastatic melanoma (n = 25) underwent surgery; all had intraoperative findings of intussusception and/or metastatic melanoma except 1 (Meckel's diverticulum). CONCLUSION: Asymptomatic patients with NED do not require surgery and intussusception will likely resolve spontaneously. Asymptomatic patients with known metastatic melanoma may be initially observed, but a low threshold for surgery should be maintained. Symptomatic patients with known metastases should undergo surgery.

9 Article Adjuvant and Neoadjuvant Therapy in High-Risk Stage III Cutaneous Melanoma. 2017

Sondak, Vernon K / Khushalani, Nikhil I. ·Department of Cutaneous Oncology, Moffitt Cancer Center, and Department of Oncologic Sciences, USF Morsani College of Medicine, Tampa, Florida. ·Int J Radiat Oncol Biol Phys · Pubmed #28586957.

ABSTRACT: -- No abstract --

10 Article Regional Radiation Therapy Impacts Outcome for Node-Positive Cutaneous Melanoma. 2017

Strom, Tobin / Torres-Roca, Javier F / Parekh, Akash / Naghavi, Arash O / Caudell, Jimmy J / Oliver, Daniel E / Messina, Jane L / Khushalani, Nikhil I / Zager, Jonathan S / Sarnaik, Amod / Mulé, James J / Trotti, Andy M / Eschrich, Steven A / Sondak, Vernon K / Harrison, Louis B. ·From Department of Radiation Oncology, Moffitt Cancer Center; Department of Oncologic Sciences, University of South Florida Morsani College of Medicine; Department of Cutaneous Oncology, Moffitt Cancer Center; Department of Pathology & Cell Biology and Dermatology, University of South Florida Morsani College of Medicine; Center for Translational Research, Moffitt Cancer Center; and Department of Biomedical Informatics, Moffitt Cancer Center, Tampa, Florida. ·J Natl Compr Canc Netw · Pubmed #28404758.

ABSTRACT:

11 Article Clinical outcomes of melanoma brain metastases treated with stereotactic radiosurgery and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitor, or conventional chemotherapy. 2016

Ahmed, K A / Abuodeh, Y A / Echevarria, M I / Arrington, J A / Stallworth, D G / Hogue, C / Naghavi, A O / Kim, S / Kim, Y / Patel, B G / Sarangkasiri, S / Johnstone, P A S / Sahebjam, S / Khushalani, N I / Forsyth, P A / Harrison, L B / Yu, M / Etame, A B / Caudell, J J. ·Department of Radiation Oncology. · Department of Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa. · Department of School of Medicine, University of Louisville, Louisville. · Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa. · Department of Morsani College of Medicine, University of South Florida, Tampa. · Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa. · Department of Cutaneous-Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. · Department of Radiation Oncology jimmy.caudell@moffitt.org. ·Ann Oncol · Pubmed #27637745.

ABSTRACT: BACKGROUND: The effect of immunologic and targeted agents on intracranial response rates in patients with melanoma brain metastases (MBMs) is not yet clearly understood. This report analyzes outcomes of intact MBMs treated with single-session stereotactic radiosurgery (SRS) and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors(i), BRAFi, or conventional chemotherapy. PATIENTS AND METHODS: Patients were included if MBMs were treated with single-session SRS within 3 months of receiving systemic therapy. The primary end point of this study was distant MBM control. Secondary end points were local MBM control defined as a >20% volume increase on follow-up MRI, systemic progression-free survival, overall survival (OS) from both SRS and cranial metastases diagnosis, and neurotoxicity. Images were reviewed alongside two neuro-radiologists at our institution. RESULTS: Ninety-six patients were treated to 314 MBMs over 119 SRS treatment sessions between January 2007 and August 2015. No significant differences were noted in age (P = 0.27), gender (P = 0.85), treated gross tumor volume (P = 0.26), or the diagnosis-specific graded prognostic assessment (P = 0.51) between the treatment cohorts. Twelve-month Kaplan-Meier (KM) distant MBM control rates were 38%, 21%, 20%, 8%, and 5% (P = 0.008) for SRS with anti-PD-1 therapies, anti-CTLA-4 therapy, BRAF/MEKi, BRAFi, and conventional chemotherapy, respectively. No significant differences were noted in the KM local MBM control rates among treatment groups (P = 0.25). Treatment with anti-PD-1 therapy, anti-CTLA-4 therapy, or BRAF/MEKi significantly improved OS on both univariate and multivariate analyses when compared with conventional chemotherapy. CONCLUSION: In our institutional analysis of patients treated with SRS and various systemic immunologic and targeted melanoma agents, significant differences in distant MBM control and OS are noted. Prospective evaluation of the potential synergistic effect between these agents and SRS is warranted.

12 Article Are we there yet? Prolonged MAPK inhibition in BRAF(V600)-mutant melanoma. 2016

Khushalani, Nikhil I / Sondak, Vernon K. ·Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA. Electronic address: vernon.sondak@moffitt.org. ·Lancet Oncol · Pubmed #27480104.

ABSTRACT: -- No abstract --

13 Article Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders. 2016

Johnson, Douglas B / Sullivan, Ryan J / Ott, Patrick A / Carlino, Matteo S / Khushalani, Nikhil I / Ye, Fei / Guminski, Alexander / Puzanov, Igor / Lawrence, Donald P / Buchbinder, Elizabeth I / Mudigonda, Tejaswi / Spencer, Kristen / Bender, Carolin / Lee, Jenny / Kaufman, Howard L / Menzies, Alexander M / Hassel, Jessica C / Mehnert, Janice M / Sosman, Jeffrey A / Long, Georgina V / Clark, Joseph I. ·Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. · Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. · Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts. · Department of Medicine, Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, New South Wales, Australia5Department of Medicine, University of Sydney, Sydney, New South Wales, Australia. · Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York. · Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee. · Department of Medicine, University of Sydney, Sydney, New South Wales, Australia8Department of Medicine, Melanoma Institute Australia, Sydney, New South Wales, Australia. · medical student at School of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. · Department of Medicine, Rutgers Cancer Institute of New Jersey, New Brunswick. · Department of Medicine, Heidelberg University Hospital, Heidelberg, Germany. · Department of Medicine, Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, New South Wales, Australia8Department of Medicine, Melanoma Institute Australia, Sydney, New South Wales, Australia. · Department of Surgery, Rutgers Cancer Institute of New Jersey, New Brunswick. · Department of Medicine, Loyola University Medical Center, Maywood, Illinois. ·JAMA Oncol · Pubmed #26633184.

ABSTRACT: IMPORTANCE: Ipilimumab and other immune therapies are effective treatment options for patients with advanced melanoma but cause frequent immune-related toxic effects. Autoimmune diseases are common, and the safety and efficacy of ipilimumab therapy in patients with preexisting autoimmune disorders is not known. OBJECTIVE: To determine the safety and efficacy of ipilimumab therapy in patients with advanced melanoma with preexisting autoimmune disorders. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of patients with advanced melanoma and preexisting autoimmune disorders who received ipilimumab at 9 academic tertiary referral centers from January 1, 2012, through August 1, 2015. The data analysis was performed on August 24, 2015. EXPOSURE: Ipilimumab therapy. MAIN OUTCOMES AND MEASURES: Safety, in terms of frequency of autoimmune flares and conventional immune-related adverse events (irAEs), and efficacy, in terms of response rates and overall survival, were evaluated descriptively. RESULTS: Of the 30 patients who received ipilimumab (17 [57%] male; median [range] age, 59.5 [30-80] y), 6 had rheumatoid arthritis, 5 had psoriasis, 6 had inflammatory bowel disease, 2 had systemic lupus erythematosus, 2 had multiple sclerosis, 2 had autoimmune thyroiditis, and 7 had other conditions. Thirteen patients (43%) were receiving immunosuppressive therapy at the time of initiation of ipilimumab therapy, most commonly low-dose prednisone or hydroxychloroquine. With ipilimumab treatment, 8 patients (27%) experienced exacerbations of their autoimmune condition necessitating systemic treatment; all were managed with corticosteroids. Conventional grade 3 to 5 irAEs occurred in 10 patients (33%) and were reversible with corticosteroids or with infliximab therapy in 2 cases. One patient with baseline psoriasis died of presumed immune-related colitis after a 1-week delay prior to reporting symptoms. Fifteen patients (50%) had neither autoimmune disease flares nor irAEs. Six patients experienced an objective response (20%), including 1 with a durable complete response. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the largest series of patients with preexisting autoimmune disease treated with immune checkpoint inhibitors. Ipilimumab was clinically active and was associated with exacerbations of autoimmune disease and conventional ipilimumab-induced irAEs that were readily manageable with standard therapies when started in a timely fashion. Ipilimumab therapy may be considered in this setting with vigilant clinical monitoring.

14 Article Dose rounding of ipilimumab in adult metastatic melanoma patients results in significant cost savings. 2014

Jarkowski, Anthony / Nestico, Jill S / Vona, Karen L / Khushalani, Nikhil I. ·James P Wilmot Cancer Center at the University of Rochester Medical Center, Rochester, NY, USA. ·J Oncol Pharm Pract · Pubmed #23512270.

ABSTRACT: PURPOSE: To assess cost savings incurred with a dose rounding process that was implemented for ipilimumab. Secondarily, to assess response rates, patient tolerance, and adverse effects associated with ipilimumab upon implementation of dose rounding. METHODS: All patients with a diagnosis of metastatic melanoma and who received at least one dose ipilimumab were included for analysis. Doses of ipilimumab were calculated based upon the actual body weight (in kg) of the patient at the FDA approved regimen of 3 mg/kg every 21 days × 4 doses. The exact total mg dose was then rounded to the nearest 50 mg vial size. The potential effect on cost was calculated in US dollars for both the calculated and rounded doses. Waste, in mg, was defined as the amount of drug that may have been discarded if the calculated dose was used for therapy. The acquisition cost applied was US$120 per mg. RESULTS: 22 patients have received at least one dose of ipilimumab. 11 patients have completed therapy and received all four induction doses. 9 patients discontinued therapy early and 2 patients were still actively receiving induction at the time of this analysis. A total of 63 doses were given. The maximum potential cost savings by giving ipilimumab to the nearest 50 mg over the period was 155,400. CONCLUSIONS: Dose rounding of ipilimumab to the nearest 50 mg has the potential to result in a significant cost savings by eliminating drug waste.