Nivolumab plus Ipilimumab in Advanced Melanoma
Jedd D. Wolchok,Harriet Kluger,Margaret K. Callahan,Michael A. Postow,Naiyer A. Rizvi,Alexander M. Lesokhin,Neil H. Segal,Charlotte E. Ariyan,Ruth-Ann Gordon,Kathleen Reed,Matthew M. Burke,Anne Caldwell,Stephanie Anne Kronenberg,Blessing Agunwamba,Xiaoling Zhang,Israel Lowy,Hector David Inzunza,William Feely,Christine Horak,Quan Hong,Alan J. Korman,Jon M. Wigginton,Ashok Kumar Gupta,Mario Sznol +23 more
TLDR
Conurrent therapy with nivolumab and ipilimumab had a manageable safety profile and provided clinical activity that appears to be distinct from that in published data on monotherapy, with rapid and deep tumor regression in a substantial proportion of patients.Abstract:
A total of 53 patients received concurrent therapy with nivolumab and ipilimumab, and 33 received sequenced treatment. The objective-response rate (according to modified World Health Organization criteria) for all patients in the concurrent-regimen group was 40%. Evidence of clinical activity (conventional, unconfirmed, or immune-related response or stable disease for ≥24 weeks) was observed in 65% of patients. At the maximum doses that were associated with an acceptable level of adverse events (nivolumab at a dose of 1 mg per kilogram of body weight and ipilimumab at a dose of 3 mg per kilogram), 53% of patients had an objective response, all with tumor reduction of 80% or more. Grade 3 or 4 adverse events related to therapy occurred in 53% of patients in the concurrent-regimen group but were qualitatively similar to previous experience with monotherapy and were generally reversible. Among patients in the sequenced-regimen group, 18% had grade 3 or 4 adverse events related to therapy and the objective-response rate was 20%. CONCLUSIONS Concurrent therapy with nivolumab and ipilimumab had a manageable safety profile and provided clinical activity that appears to be distinct from that in published data on monotherapy, with rapid and deep tumor regression in a substantial proportion of patients. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; ClinicalTrials.gov number, NCT01024231.)read more
Citations
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PD-1/PD-L1 inhibitors.
Joel C. Sunshine,Janis M. Taube +1 more
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TL;DR: Combination checkpoint blockade with PD-1 plus cytotoxic T-lymphocyte antigen (CTLA)-4 blockade appears to improve response rates in patients who are less likely to respond to single-checkpoint blockade.
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Melanoma cell-intrinsic PD-1 receptor functions promote tumor growth
Sonja Kleffel,Christian Posch,Steven R. Barthel,Hansgeorg Mueller,Hansgeorg Mueller,Christoph Schlapbach,Emmanuella Guenova,Christopher P. Elco,Nayoung Lee,Vikram R. Juneja,Qian Zhan,Christine G. Lian,Rahel Thomi,Wolfram Hoetzenecker,Antonio Cozzio,Reinhard Dummer,Martin C. Mihm,Keith T. Flaherty,Markus H. Frank,Markus H. Frank,Markus H. Frank,George F. Murphy,Arlene H. Sharpe,Arlene H. Sharpe,Thomas S. Kupper,Tobias Schatton,Tobias Schatton +26 more
TL;DR: It is shown that murine and human melanomas contain PD-1-expressing cancer subpopulations and demonstrated that melanoma cell-intrinsic PD- 1 promotes tumorigenesis, even in mice lacking adaptive immunity, and suggested that blocking melanoma-PD-1 might contribute to the striking clinical efficacy of anti-PD -1 therapy.
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Vitiligo-Like Depigmentation in Patients With Stage III-IV Melanoma Receiving Immunotherapy and Its Association With Survival: A Systematic Review and Meta-Analysis
Hansje Eva Teulings,Jacqueline Limpens,Sophia N. Jansen,Aeilko H. Zwinderman,Johannes B. Reitsma,Phyllis I. Spuls,Rosalie M. Luiten +6 more
TL;DR: Although vitiligo occurs only in a low percentage of patients with melanoma treated with immunotherapy, the findings suggest clear survival benefit in these patients.
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Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer.
Juan C. Osorio,Ai Ni,Jamie E. Chaft,R. Pollina,M.K. Kasler,Dennis Stephens,Carlos J. Rodriguez,L. Cambridge,Hira Rizvi,Jedd D. Wolchok,Taha Merghoub,Charles M. Rudin,Stephanie Fish,Matthew D. Hellmann,Matthew D. Hellmann +14 more
TL;DR: Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset, frequently preceded by transient hyperthyroidism, closely associated with anti-thyroid antibodies, and may be associated with improved outcomes.
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