BACKGROUND: Patients with advanced melanoma have a poor outcome. We hypothesize that combination immunotherapy can synergistically activate host immunity to generate an effective treatment for patients with high-risk, resected stage 3, recurrent, refractory, or stage 4 melanoma. METHODS: We conducted a phase 2 clinical trial of HyperAcute Melanoma (HAM) vaccine (NLG-12036, NewLink Genetics) combined with pegylated interferon (Sylatron, Merck). Trial design consisted of a 12-week regimen with the initial 4 weekly treatments consisting of HAM alone (intradermally) followed by 8 additional treatments of HAM plus Sylatron (subcutaneously, 6 μg/kg). Trial endpoint outcomes include clinical response, overall safety, and correlative findings for observed antitumor effect. RESULTS: Our cohort consisted of 25 patients with a median age of 60. Twenty-one patients completed the trial and 4 stopped because of progressive disease (PD). According to the Response Evaluation Criteria in Solid Tumors, of the 16 stage 4 patients, 2 had a complete response (CR), 1 had stable disease, and 4 had no evidence of disease (NED) after resection. For stage 2/3 patients, 3 of 9 remained NED, and the 1 stage 2C patient had slow PD with a single site resected and is currently NED. The median overall survival time was 29 months, with 60% of the patients surviving for >1 year. Of the 25 patients, 12 (48%) are still alive. All evaluable patients (21/21) seroconverted, developing autoimmune antibodies. Four of 25 patients developed vitiligo, correlating with 2 CR patients and 2 NED patients. CONCLUSION: Combination immunotherapy with HAM plus Sylatron shows clinical efficacy with tumor regression and concomitant immune activation. Optimization of dosing schedules and therapeutic efficacy should be further explored to enhance the benefit of this promising immunotherapeutic approach.
BACKGROUND:Patients with advanced melanoma have a poor outcome. We hypothesize that combination immunotherapy can synergistically activate host immunity to generate an effective treatment for patients with high-risk, resected stage 3, recurrent, refractory, or stage 4 melanoma. METHODS: We conducted a phase 2 clinical trial of HyperAcute Melanoma (HAM) vaccine (NLG-12036, NewLink Genetics) combined with pegylated interferon (Sylatron, Merck). Trial design consisted of a 12-week regimen with the initial 4 weekly treatments consisting of HAM alone (intradermally) followed by 8 additional treatments of HAM plus Sylatron (subcutaneously, 6 μg/kg). Trial endpoint outcomes include clinical response, overall safety, and correlative findings for observed antitumor effect. RESULTS: Our cohort consisted of 25 patients with a median age of 60. Twenty-one patients completed the trial and 4 stopped because of progressive disease (PD). According to the Response Evaluation Criteria in Solid Tumors, of the 16 stage 4 patients, 2 had a complete response (CR), 1 had stable disease, and 4 had no evidence of disease (NED) after resection. For stage 2/3 patients, 3 of 9 remained NED, and the 1 stage 2C patient had slow PD with a single site resected and is currently NED. The median overall survival time was 29 months, with 60% of the patients surviving for >1 year. Of the 25 patients, 12 (48%) are still alive. All evaluable patients (21/21) seroconverted, developing autoimmune antibodies. Four of 25 patients developed vitiligo, correlating with 2 CR patients and 2 NED patients. CONCLUSION: Combination immunotherapy with HAM plus Sylatron shows clinical efficacy with tumor regression and concomitant immune activation. Optimization of dosing schedules and therapeutic efficacy should be further explored to enhance the benefit of this promising immunotherapeutic approach.
Authors: Marna G Bouwhuis; Stefan Suciu; Alessandro Testori; Wim H Kruit; François Salès; Poulam Patel; Cornelis J Punt; Mario Santinami; Alain Spatz; Timo L M Ten Hagen; Alexander M M Eggermont Journal: J Clin Oncol Date: 2010-04-12 Impact factor: 44.544
Authors: M Grace; S Youngster; G Gitlin; W Sydor; L Xie; L Westreich; S Jacobs; D Brassard; J Bausch; R Bordens Journal: J Interferon Cytokine Res Date: 2001-12 Impact factor: 2.607
Authors: Katelyn T Byrne; Anik L Côté; Peisheng Zhang; Shannon M Steinberg; Yanxia Guo; Rameeza Allie; Weijun Zhang; Marc S Ernstoff; Edward J Usherwood; Mary Jo Turk Journal: J Clin Invest Date: 2011-04-11 Impact factor: 14.808
Authors: Ronald M Bukowski; Craig Tendler; David Cutler; Esther Rose; Mark M Laughlin; Paul Statkevich Journal: Cancer Date: 2002-07-15 Impact factor: 6.860
Authors: Gabriela R Rossi; Mario R Mautino; Dana Z Awwad; Katie Husske; Henry Lejukole; Marie Koenigsfeld; William J Ramsey; Nicholas Vahanian; Charles J Link Journal: J Immunother Date: 2008 Jul-Aug Impact factor: 4.456
Authors: Bettina C Baumann; Pietro Forte; Robert J Hawley; Robert Rieben; Mårten K J Schneider; Jörg D Seebach Journal: J Immunol Date: 2004-05-15 Impact factor: 5.422
Authors: Kinsey A McCormick; Andrew L Coveler; Gabriela R Rossi; Nicholas N Vahanian; Charles Link; E Gabriela Chiorean Journal: Hum Vaccin Immunother Date: 2016-03-03 Impact factor: 3.452
Authors: Andrew W Hahn; Charles Drake; Samuel R Denmeade; Yousef Zakharia; Benjamin L Maughan; Eugene Kennedy; Charles Link; Nicholas Vahanian; Hans Hammers; Neeraj Agarwal Journal: Oncologist Date: 2019-09-06
Authors: Stephen M Shaw; Jenny Middleton; Kim Wigglesworth; Amber Charlemagne; Oliver Schulz; Melanie S Glossop; Giles F Whalen; Robert Old; Mike Westby; Chris Pickford; Rinat Tabakman; Irit Carmi-Levy; Abi Vainstein; Ella Sorani; Arik A Zur; Sascha A Kristian Journal: Cancer Cell Int Date: 2019-12-19 Impact factor: 5.722