Adriana Hepner1, Victoria G Atkinson2, James Larkin3, Rebecca A Burrell3, Matteo S Carlino4, Douglas B Johnson5, Lisa Zimmer6, Katy K Tsai7, Oliver Klein8, Serigne N Lo9, Andrew Haydon10, Prachi Bhave11, Megan Lyle12, Lalit Pallan9, Ines Pires da Silva9, Camille Gerard13, Olivier Michielin13, Georgina V Long14, Alexander M Menzies15. 1. Melanoma Institute Australia, The University of Sydney, NSW, Australia; Instituto do Cancer do Estado de Sao Paulo, SP, Brazil. 2. University of QLD and Princess Alexandra and Greenslopes Private Hospital, Brisbane, Australia. 3. The Royal Marsden, NHS Foundation Trust, London, UK. 4. Melanoma Institute Australia, The University of Sydney, NSW, Australia; Crown Princess Mary Cancer Centre Westmead and Blacktown Hospitals, Australia. 5. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. 6. Department of Dermatology, University Hospital Essen, Essen, Germany. 7. Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, CA, USA. 8. Olivia Newton-John Cancer Centre and Austin Health, Melbourne, Australia. 9. Melanoma Institute Australia, The University of Sydney, NSW, Australia. 10. Alfred Health, Melbourne, Australia; Monash University, Melbourne, Australia. 11. Monash University, Melbourne, Australia. 12. Cairns Private Hospital, Cairns, Australia. 13. Department of Oncology, Lausanne University Hospital CHUV, Lausanne, Switzerland. 14. Melanoma Institute Australia, The University of Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Royal North Shore and Mater Hospitals, NSW, Australia. 15. Melanoma Institute Australia, The University of Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Royal North Shore and Mater Hospitals, NSW, Australia. Electronic address: alexander.menzies@sydney.edu.au.
Abstract
PURPOSE: Combination immunotherapy with nivolumab and ipilimumab has a high initial response rate in advanced melanoma; however, up to 55% of patients later progress. The efficacy and safety of ipilimumab re-induction in the setting of acquired resistance (AR) to combination immunotherapy is unknown. METHODS: Patients with advanced melanoma who initially achieved a complete response, partial response or sustained stable disease to induction combination immunotherapy then progressed and were reinduced with ipilimumab (alone or in combination with anti-PD-1) and were analysed retrospectively. Demographics, disease characteristics, efficacy and toxicity were examined. RESULTS: Forty-seven patients were identified from 12 centres. The response rate to reinduction therapy was 12/47 (26%), and disease control rate was 21/47 (45%). Responses appeared more frequent in patients who developed AR after ceasing induction immunotherapy (30% vs. 18%, P = 0.655). Time to AR was 11 months (95% confidence interval [CI], 8-15 months). After a median follow-up of 16 months (95% CI, 10-25 months), responders to reinduction had a median progression-free survival of 14 months (95% CI, 13, NR months), and in the whole cohort, the median overall survival from reinduction was 17 months (95% CI, 12-NR months). Twenty-seven (58%) immune-related adverse events (irAEs) were reported; 18 (38%) were grade 3/4, and in 11 of 27 (40%), the same irAE observed during induction therapy recurred. CONCLUSIONS: Reinduction with ipilimumab ± anti-PD-1 has modest clinical activity. Clinicians should be attentive to the risk of irAEs, including recurrence of irAEs that occurred during induction therapy. Future studies are necessary to determine best management after resistance to combination immunotherapy.
PURPOSE: Combination immunotherapy with nivolumab and ipilimumab has a high initial response rate in advanced melanoma; however, up to 55% of patients later progress. The efficacy and safety of ipilimumab re-induction in the setting of acquired resistance (AR) to combination immunotherapy is unknown. METHODS: Patients with advanced melanoma who initially achieved a complete response, partial response or sustained stable disease to induction combination immunotherapy then progressed and were reinduced with ipilimumab (alone or in combination with anti-PD-1) and were analysed retrospectively. Demographics, disease characteristics, efficacy and toxicity were examined. RESULTS: Forty-seven patients were identified from 12 centres. The response rate to reinduction therapy was 12/47 (26%), and disease control rate was 21/47 (45%). Responses appeared more frequent in patients who developed AR after ceasing induction immunotherapy (30% vs. 18%, P = 0.655). Time to AR was 11 months (95% confidence interval [CI], 8-15 months). After a median follow-up of 16 months (95% CI, 10-25 months), responders to reinduction had a median progression-free survival of 14 months (95% CI, 13, NR months), and in the whole cohort, the median overall survival from reinduction was 17 months (95% CI, 12-NR months). Twenty-seven (58%) immune-related adverse events (irAEs) were reported; 18 (38%) were grade 3/4, and in 11 of 27 (40%), the same irAE observed during induction therapy recurred. CONCLUSIONS: Reinduction with ipilimumab ± anti-PD-1 has modest clinical activity. Clinicians should be attentive to the risk of irAEs, including recurrence of irAEs that occurred during induction therapy. Future studies are necessary to determine best management after resistance to combination immunotherapy.
Authors: Paul B Chapman; Vetri Sudar Jayaprakasam; Katherine S Panageas; Margaret Callahan; Michael A Postow; Alexander N Shoushtari; Jedd D Wolchok; Allison Betof Warner Journal: J Immunother Cancer Date: 2021-10 Impact factor: 13.751
Authors: Elias A T Koch; Anne Petzold; Anja Wessely; Edgar Dippel; Anja Gesierich; Ralf Gutzmer; Jessica C Hassel; Sebastian Haferkamp; Katharina C Kähler; Harald Knorr; Nicole Kreuzberg; Ulrike Leiter; Carmen Loquai; Friedegund Meier; Markus Meissner; Peter Mohr; Claudia Pföhler; Farnaz Rahimi; Dirk Schadendorf; Beatrice Schell; Max Schlaak; Patrick Terheyden; Kai-Martin Thoms; Beatrice Schuler-Thurner; Selma Ugurel; Jens Ulrich; Jochen Utikal; Michael Weichenthal; Fabian Ziller; Carola Berking; Markus V Heppt Journal: Cancers (Basel) Date: 2022-01-20 Impact factor: 6.639