Durable responses in patients with genitourinary cancers following immune checkpoint therapy rechallenge after moderate-to-severe immune-related adverse events
Background Immune checkpoint therapy (ICT) prolongs survival in subsets of patients with cancer but can also trigger immune-related adverse events (irAEs) requiring treatment discontinuation. Recent studies have investigated safety of ICT rechallenge after irAEs, and evidence suggests that rechallen...
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BMJ Publishing Group
2021-07-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/9/7/e002850.full |
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| author | Jennifer Wang Jianjun Gao Pavlos Msaouel Padmanee Sharma Nizar Tannir Sumit K Subudhi Eric Jonasch Amishi Shah Matthew T Campbell Bilal A Siddiqui Jinesh S Gheeya Rohit Goswamy Tharakeswara K Bathala Devaki Shilpa Surasi Sangeeta Goswami Amado J Zurita Paul G Corn Ana M Aparicio Arlene O Siefker-Radtke |
| author_facet | Jennifer Wang Jianjun Gao Pavlos Msaouel Padmanee Sharma Nizar Tannir Sumit K Subudhi Eric Jonasch Amishi Shah Matthew T Campbell Bilal A Siddiqui Jinesh S Gheeya Rohit Goswamy Tharakeswara K Bathala Devaki Shilpa Surasi Sangeeta Goswami Amado J Zurita Paul G Corn Ana M Aparicio Arlene O Siefker-Radtke |
| author_sort | Jennifer Wang |
| collection | DOAJ |
| description | Background Immune checkpoint therapy (ICT) prolongs survival in subsets of patients with cancer but can also trigger immune-related adverse events (irAEs) requiring treatment discontinuation. Recent studies have investigated safety of ICT rechallenge after irAEs, and evidence suggests that rechallenge may be associated with improved antitumor responses. However, data are limited on response duration after ICT rechallenge, particularly after severe irAEs.Objective To evaluate safety and efficacy of ICT rechallenge after moderate-to-severe irAEs in patients with renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer.Methods In this retrospective cohort study, medical records from September 25, 2013, to June 1, 2020, for patients with genitourinary (GU) cancers at MD Anderson Cancer Center who were rechallenged with the same or different ICT following irAEs were reviewed. Demographics, ICT exposure, irAEs (grade and treatment), ICT discontinuation or rechallenge, rates of subsequent irAEs (new or recurrent) and antitumor activity (objective response rates and response duration) were reviewed.Results Sixty-one patients with RCC, UC, and prostate cancer were rechallenged with ICT after experiencing 105 total irAEs. Objective response rates after rechallenge, that is, upgrade in response, were 14% in RCC (4/28), 21% in UC (3/14), and 0% in prostate cancer. All seven patients who achieved upgrade in response had initial grade 2 or 3 irAEs. Responses were durable among these seven patients, with median radiographic progression-free survival not reached (range: 3.7–66.4 months) as of the March 8, 2021, data cut-off (median follow-up 40.9 months (95% CI 35.3 to 46.5)). All achieved complete response except one patient who was lost to follow-up. The rate of subsequent grade 3 or 4 irAEs after rechallenge was 30%, with no fatal irAEs. The rate of recrudescence of the same irAE was 26% (16/61). 54% of patients received corticosteroids (33/61), and 21% received targeted immunosuppression (13/61) for the initial irAEs.Conclusions and relevance ICT rechallenge after moderate-to-severe irAEs was associated with deep and durable responses in a subset of patients with RCC and UC, with acceptable safety and no fatal events. Strategies to enable ICT resumption after moderate-to-severe irAEs, such targeted immunosuppression, warrant further study. |
| format | Article |
| id | doaj-art-cda99109c2c04a0cb9747cd3f91c2b17 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2021-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-cda99109c2c04a0cb9747cd3f91c2b172025-08-20T02:12:57ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-07-019710.1136/jitc-2021-002850Durable responses in patients with genitourinary cancers following immune checkpoint therapy rechallenge after moderate-to-severe immune-related adverse eventsJennifer Wang0Jianjun Gao1Pavlos Msaouel2Padmanee Sharma3Nizar Tannir4Sumit K Subudhi5Eric Jonasch6Amishi Shah7Matthew T Campbell8Bilal A Siddiqui9Jinesh S Gheeya10Rohit Goswamy11Tharakeswara K Bathala12Devaki Shilpa Surasi13Sangeeta Goswami14Amado J Zurita15Paul G Corn16Ana M Aparicio17Arlene O Siefker-Radtke18Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USAAff2 grid.240145.60000000122914776Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center Unit 1374, 1155 Pressler Street 77030-3721 Houston TX USAGenitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA1The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA1The Ohio State University, Columbus, OH, USADepartment of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USADepartment of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA1The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USABackground Immune checkpoint therapy (ICT) prolongs survival in subsets of patients with cancer but can also trigger immune-related adverse events (irAEs) requiring treatment discontinuation. Recent studies have investigated safety of ICT rechallenge after irAEs, and evidence suggests that rechallenge may be associated with improved antitumor responses. However, data are limited on response duration after ICT rechallenge, particularly after severe irAEs.Objective To evaluate safety and efficacy of ICT rechallenge after moderate-to-severe irAEs in patients with renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer.Methods In this retrospective cohort study, medical records from September 25, 2013, to June 1, 2020, for patients with genitourinary (GU) cancers at MD Anderson Cancer Center who were rechallenged with the same or different ICT following irAEs were reviewed. Demographics, ICT exposure, irAEs (grade and treatment), ICT discontinuation or rechallenge, rates of subsequent irAEs (new or recurrent) and antitumor activity (objective response rates and response duration) were reviewed.Results Sixty-one patients with RCC, UC, and prostate cancer were rechallenged with ICT after experiencing 105 total irAEs. Objective response rates after rechallenge, that is, upgrade in response, were 14% in RCC (4/28), 21% in UC (3/14), and 0% in prostate cancer. All seven patients who achieved upgrade in response had initial grade 2 or 3 irAEs. Responses were durable among these seven patients, with median radiographic progression-free survival not reached (range: 3.7–66.4 months) as of the March 8, 2021, data cut-off (median follow-up 40.9 months (95% CI 35.3 to 46.5)). All achieved complete response except one patient who was lost to follow-up. The rate of subsequent grade 3 or 4 irAEs after rechallenge was 30%, with no fatal irAEs. The rate of recrudescence of the same irAE was 26% (16/61). 54% of patients received corticosteroids (33/61), and 21% received targeted immunosuppression (13/61) for the initial irAEs.Conclusions and relevance ICT rechallenge after moderate-to-severe irAEs was associated with deep and durable responses in a subset of patients with RCC and UC, with acceptable safety and no fatal events. Strategies to enable ICT resumption after moderate-to-severe irAEs, such targeted immunosuppression, warrant further study.https://jitc.bmj.com/content/9/7/e002850.full |
| spellingShingle | Jennifer Wang Jianjun Gao Pavlos Msaouel Padmanee Sharma Nizar Tannir Sumit K Subudhi Eric Jonasch Amishi Shah Matthew T Campbell Bilal A Siddiqui Jinesh S Gheeya Rohit Goswamy Tharakeswara K Bathala Devaki Shilpa Surasi Sangeeta Goswami Amado J Zurita Paul G Corn Ana M Aparicio Arlene O Siefker-Radtke Durable responses in patients with genitourinary cancers following immune checkpoint therapy rechallenge after moderate-to-severe immune-related adverse events Journal for ImmunoTherapy of Cancer |
| title | Durable responses in patients with genitourinary cancers following immune checkpoint therapy rechallenge after moderate-to-severe immune-related adverse events |
| title_full | Durable responses in patients with genitourinary cancers following immune checkpoint therapy rechallenge after moderate-to-severe immune-related adverse events |
| title_fullStr | Durable responses in patients with genitourinary cancers following immune checkpoint therapy rechallenge after moderate-to-severe immune-related adverse events |
| title_full_unstemmed | Durable responses in patients with genitourinary cancers following immune checkpoint therapy rechallenge after moderate-to-severe immune-related adverse events |
| title_short | Durable responses in patients with genitourinary cancers following immune checkpoint therapy rechallenge after moderate-to-severe immune-related adverse events |
| title_sort | durable responses in patients with genitourinary cancers following immune checkpoint therapy rechallenge after moderate to severe immune related adverse events |
| url | https://jitc.bmj.com/content/9/7/e002850.full |
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