Ammar Sukari1, Misako Nagasaka2,3, Roba Alhasan4, Dhaval Patel2, Antoinette Wozniak5, Radhakrishnan Ramchandren2, Ulka Vaishampayan2, Amy Weise2, Lawrence Flaherty2, Hyejeong Jang2, Seongho Kim2, Shirish Gadgeel6. 1. Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, U.S.A. sukaria@karmanos.org. 2. Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, U.S.A. 3. Department of Advanced Medical Innovation, St. Marianna University Graduate School of Medicine, Kawasaki, Japan. 4. Department of Hematology and Oncology, Michigan State University, Lansing, MI, U.S.A. 5. Department of Oncology, University of Pittsburgh, Pittsburgh, PA, U.S.A. 6. Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, U.S.A.
Abstract
BACKGROUND: Data on the characteristics of patients who are likely to experience adverse events, both immune-related and non-immune-related, from programmed cell death-1 (PD1) inhibitors are limited. PATIENTS AND METHODS: Data from patients who received ≥1 dose of single-agent PD1 inhibitor between August 3, 2011 and August 31, 2016 were obtained from our Institution's pharmacy database. AEs were graded using Common Terminology Criteria for Adverse Events version 4. RESULTS: One hundred and eighty-two patients received at least one dose of single-agent PD1 inhibitor prior to data cut-off. After excluding 14 patients with uncommon malignancies, the total number of patients were 168. The median age was 63 (range=24-92) years. There were 87 (52%) cases of non-small cell lung cancer (NSCLC), 35 (21%) of renal cell carcinoma (RCC), 12 (7%) of melanoma, 18 (11%) of Hodgkin's lymphomas, eight (5%) of head and neck squamous cell carcinoma (HNSCC) and eight (5%) of small cell lung cancer. Considering grade 2 or more AEs, 30 (18%) patients had kidney injury, 34 (20%) hypothyroidism, 36 (21%) transaminitis, 20 (12%) pneumonitis, and 18 (11%) colitis. Patients with RCC had higher odds of experiencing grade 2 or more kidney injury than patients with other primary tumor types (adjusted p=0.025), whereas patients with Hodgkin's lymphoma and HNSCC had higher odds of grade 2 hypothyroidism (adjusted p=0.005). Patients with NSCLC had higher risk of death with pneumonitis than those whose primary cancer was not NSCLC (adjusted p=0.005). DISCUSSION: The increased odds of patients with Hodgkin's lymphoma and HNSCC experiencing grade 2 or more hypothyroidism may be related to previous radiation exposure. Most patients with RCC had undergone nephrectomy, making them more susceptible to acute kidney injury. When pneumonitis occurred in patients with primary NSCLC, the overall survival was significantly worse. The duration of PD1 therapy was significantly associated with onset of pneumonitis (p=0.007). CONCLUSION: The site of primary tumor or metastasis may help predict the most common AEs in patients treated with PD1 inhibitors. Copyright
BACKGROUND: Data on the characteristics of patients who are likely to experience adverse events, both immune-related and non-immune-related, from programmed cell death-1 (PD1) inhibitors are limited. PATIENTS AND METHODS: Data from patients who received ≥1 dose of single-agent PD1 inhibitor between August 3, 2011 and August 31, 2016 were obtained from our Institution's pharmacy database. AEs were graded using Common Terminology Criteria for Adverse Events version 4. RESULTS: One hundred and eighty-two patients received at least one dose of single-agent PD1 inhibitor prior to data cut-off. After excluding 14 patients with uncommon malignancies, the total number of patients were 168. The median age was 63 (range=24-92) years. There were 87 (52%) cases of non-small cell lung cancer (NSCLC), 35 (21%) of renal cell carcinoma (RCC), 12 (7%) of melanoma, 18 (11%) of Hodgkin's lymphomas, eight (5%) of head and neck squamous cell carcinoma (HNSCC) and eight (5%) of small cell lung cancer. Considering grade 2 or more AEs, 30 (18%) patients had kidney injury, 34 (20%) hypothyroidism, 36 (21%) transaminitis, 20 (12%) pneumonitis, and 18 (11%) colitis. Patients with RCC had higher odds of experiencing grade 2 or more kidney injury than patients with other primary tumor types (adjusted p=0.025), whereas patients with Hodgkin's lymphoma and HNSCC had higher odds of grade 2 hypothyroidism (adjusted p=0.005). Patients with NSCLC had higher risk of death with pneumonitis than those whose primary cancer was not NSCLC (adjusted p=0.005). DISCUSSION: The increased odds of patients with Hodgkin's lymphoma and HNSCC experiencing grade 2 or more hypothyroidism may be related to previous radiation exposure. Most patients with RCC had undergone nephrectomy, making them more susceptible to acute kidney injury. When pneumonitis occurred in patients with primary NSCLC, the overall survival was significantly worse. The duration of PD1 therapy was significantly associated with onset of pneumonitis (p=0.007). CONCLUSION: The site of primary tumor or metastasis may help predict the most common AEs in patients treated with PD1 inhibitors. Copyright
Authors: Ajay V Maker; James C Yang; Richard M Sherry; Suzanne L Topalian; Udai S Kammula; Richard E Royal; Marybeth Hughes; Michael J Yellin; Leah R Haworth; Catherine Levy; Tamika Allen; Sharon A Mavroukakis; Peter Attia; Steven A Rosenberg Journal: J Immunother Date: 2006 Jul-Aug Impact factor: 4.456
Authors: Jacob Schachter; Antoni Ribas; Georgina V Long; Ana Arance; Jean-Jacques Grob; Laurent Mortier; Adil Daud; Matteo S Carlino; Catriona McNeil; Michal Lotem; James Larkin; Paul Lorigan; Bart Neyns; Christian Blank; Teresa M Petrella; Omid Hamid; Honghong Zhou; Scot Ebbinghaus; Nageatte Ibrahim; Caroline Robert Journal: Lancet Date: 2017-08-16 Impact factor: 79.321
Authors: Julie R Brahmer; Scott S Tykodi; Laura Q M Chow; Wen-Jen Hwu; Suzanne L Topalian; Patrick Hwu; Charles G Drake; Luis H Camacho; John Kauh; Kunle Odunsi; Henry C Pitot; Omid Hamid; Shailender Bhatia; Renato Martins; Keith Eaton; Shuming Chen; Theresa M Salay; Suresh Alaparthy; Joseph F Grosso; Alan J Korman; Susan M Parker; Shruti Agrawal; Stacie M Goldberg; Drew M Pardoll; Ashok Gupta; Jon M Wigginton Journal: N Engl J Med Date: 2012-06-02 Impact factor: 91.245
Authors: Troy Z Horvat; Nelly G Adel; Thu-Oanh Dang; Parisa Momtaz; Michael A Postow; Margaret K Callahan; Richard D Carvajal; Mark A Dickson; Sandra P D'Angelo; Kaitlin M Woo; Katherine S Panageas; Jedd D Wolchok; Paul B Chapman Journal: J Clin Oncol Date: 2015-08-17 Impact factor: 44.544
Authors: Robert J Motzer; Bernard Escudier; David F McDermott; Saby George; Hans J Hammers; Sandhya Srinivas; Scott S Tykodi; Jeffrey A Sosman; Giuseppe Procopio; Elizabeth R Plimack; Daniel Castellano; Toni K Choueiri; Howard Gurney; Frede Donskov; Petri Bono; John Wagstaff; Thomas C Gauler; Takeshi Ueda; Yoshihiko Tomita; Fabio A Schutz; Christian Kollmannsberger; James Larkin; Alain Ravaud; Jason S Simon; Li-An Xu; Ian M Waxman; Padmanee Sharma Journal: N Engl J Med Date: 2015-09-25 Impact factor: 91.245
Authors: Leora Horn; David R Spigel; Everett E Vokes; Esther Holgado; Neal Ready; Martin Steins; Elena Poddubskaya; Hossein Borghaei; Enriqueta Felip; Luis Paz-Ares; Adam Pluzanski; Karen L Reckamp; Marco A Burgio; Martin Kohlhäeufl; David Waterhouse; Fabrice Barlesi; Scott Antonia; Oscar Arrieta; Jérôme Fayette; Lucio Crinò; Naiyer Rizvi; Martin Reck; Matthew D Hellmann; William J Geese; Ang Li; Anne Blackwood-Chirchir; Diane Healey; Julie Brahmer; Wilfried E E Eberhardt Journal: J Clin Oncol Date: 2017-10-12 Impact factor: 44.544
Authors: Robert L Ferris; George Blumenschein; Jerome Fayette; Joel Guigay; A Dimitrios Colevas; Lisa Licitra; Kevin Harrington; Stefan Kasper; Everett E Vokes; Caroline Even; Francis Worden; Nabil F Saba; Lara C Iglesias Docampo; Robert Haddad; Tamara Rordorf; Naomi Kiyota; Makoto Tahara; Manish Monga; Mark Lynch; William J Geese; Justin Kopit; James W Shaw; Maura L Gillison Journal: N Engl J Med Date: 2016-10-08 Impact factor: 91.245
Authors: Sarah Chuzi; Fabio Tavora; Marcelo Cruz; Ricardo Costa; Young Kwang Chae; Benedito A Carneiro; Francis J Giles Journal: Cancer Manag Res Date: 2017-06-14 Impact factor: 3.989
Authors: Philippe Armand; Andreas Engert; Anas Younes; Michelle Fanale; Armando Santoro; Pier Luigi Zinzani; John M Timmerman; Graham P Collins; Radhakrishnan Ramchandren; Jonathon B Cohen; Jan Paul De Boer; John Kuruvilla; Kerry J Savage; Marek Trneny; Margaret A Shipp; Kazunobu Kato; Anne Sumbul; Benedetto Farsaci; Stephen M Ansell Journal: J Clin Oncol Date: 2018-03-27 Impact factor: 44.544
Authors: Cristina Gutierrez; Colleen McEvoy; Laveena Munshi; R Scott Stephens; Michael E Detsky; Joseph L Nates; Stephen M Pastores Journal: Crit Care Med Date: 2020-01 Impact factor: 7.598