Severe Late-Onset Grade III-IV Adverse Events under Immunotherapy: A Retrospective Study of 79 Cases
<b>Background:</b> For several decades, PD-1 has been a target in malignant melanoma (MM). PD-1 inhibitors (nivolumab, pembrolizumab) and anti-CTLA-4 (CD152) (ipilimumab) have revolutionized cancer therapy. PD-1 and CTLA-4 inhibition leads to prolonged lymphocyte effects, which explains...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/19/4928 |
| _version_ | 1797516717778272256 |
|---|---|
| author | Jean-Matthieu L’Orphelin Emilie Varey Amir Khammari Brigitte Dreno Anne Dompmartin |
| author_facet | Jean-Matthieu L’Orphelin Emilie Varey Amir Khammari Brigitte Dreno Anne Dompmartin |
| author_sort | Jean-Matthieu L’Orphelin |
| collection | DOAJ |
| description | <b>Background:</b> For several decades, PD-1 has been a target in malignant melanoma (MM). PD-1 inhibitors (nivolumab, pembrolizumab) and anti-CTLA-4 (CD152) (ipilimumab) have revolutionized cancer therapy. PD-1 and CTLA-4 inhibition leads to prolonged lymphocyte effects, which explains the cytotoxicity underlying immune-reaction-based adverse events (irAEs). Most irAEs occur in the first cycle of treatment at a median of 40 days. IrAEs of any grade have been observed in 68.2% of patients, with 10% of patients experiencing severe grade III/IV irAEs. Data on late-onset irAEs are lacking. <b>Methods:</b> Data on patients with advanced melanoma (<i>N</i> = 1862) from March 2016 to March 2021 were obtained from the RicMel database, a French national multicentric biobank dedicated to the follow-up of MM patients. Patients who received anti-PD-1 therapy or a combination therapy and experienced grade III-IV irAEs were selected and analyzed at 7 months, one year and two years after treatment was initiated. <b>Results:</b> Superficial spreading melanoma (SSM) and previous oncological drug administration before immunotherapy are significant risk factors for late-onset irAEs over 2 years after beginning immunotherapy in the univariate and multivariate analysis. The other parameters—sex, mutational status, association of immunotherapy (PD-1i and CTLA-4i) and overall response—were not significantly associated with late-onset irAEs. In our real-life data study, the median onset time of grade III-IV irAES was 128 days after the initiation of immune checkpoint inhibitors (ICI) therapy. <b>Conclusions:</b> Our study, using real-life data, suggests that patients with SSM and those who have received previous oncological treatments are more likely to experience late-onset grade III-IV irAES. Further multicentric studies with wider recruitment of patients should be performed to confirm our findings, potentially leading to changes in the recommended treatment for carefully monitored at-risk patients. |
| first_indexed | 2024-03-10T07:04:45Z |
| format | Article |
| id | doaj.art-59e2ed36d9cd42d89f5adecc8ca0eaa7 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T07:04:45Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-59e2ed36d9cd42d89f5adecc8ca0eaa72023-11-22T15:54:26ZengMDPI AGCancers2072-66942021-09-011319492810.3390/cancers13194928Severe Late-Onset Grade III-IV Adverse Events under Immunotherapy: A Retrospective Study of 79 CasesJean-Matthieu L’Orphelin0Emilie Varey1Amir Khammari2Brigitte Dreno3Anne Dompmartin4Department of Dermatology, Caen-Normandie University Hospital, 14003 Caen, FranceDepartment of Dermatology, CHU Nantes, CIC 1413, CRCINA, Nantes University, 44200 Nantes, FranceDepartment of Dermatology, CHU Nantes, CIC 1413, CRCINA, Nantes University, 44200 Nantes, FranceDepartment of Dermatology, CHU Nantes, CIC 1413, CRCINA, Nantes University, 44200 Nantes, FranceDepartment of Dermatology, Caen-Normandie University Hospital, 14003 Caen, France<b>Background:</b> For several decades, PD-1 has been a target in malignant melanoma (MM). PD-1 inhibitors (nivolumab, pembrolizumab) and anti-CTLA-4 (CD152) (ipilimumab) have revolutionized cancer therapy. PD-1 and CTLA-4 inhibition leads to prolonged lymphocyte effects, which explains the cytotoxicity underlying immune-reaction-based adverse events (irAEs). Most irAEs occur in the first cycle of treatment at a median of 40 days. IrAEs of any grade have been observed in 68.2% of patients, with 10% of patients experiencing severe grade III/IV irAEs. Data on late-onset irAEs are lacking. <b>Methods:</b> Data on patients with advanced melanoma (<i>N</i> = 1862) from March 2016 to March 2021 were obtained from the RicMel database, a French national multicentric biobank dedicated to the follow-up of MM patients. Patients who received anti-PD-1 therapy or a combination therapy and experienced grade III-IV irAEs were selected and analyzed at 7 months, one year and two years after treatment was initiated. <b>Results:</b> Superficial spreading melanoma (SSM) and previous oncological drug administration before immunotherapy are significant risk factors for late-onset irAEs over 2 years after beginning immunotherapy in the univariate and multivariate analysis. The other parameters—sex, mutational status, association of immunotherapy (PD-1i and CTLA-4i) and overall response—were not significantly associated with late-onset irAEs. In our real-life data study, the median onset time of grade III-IV irAES was 128 days after the initiation of immune checkpoint inhibitors (ICI) therapy. <b>Conclusions:</b> Our study, using real-life data, suggests that patients with SSM and those who have received previous oncological treatments are more likely to experience late-onset grade III-IV irAES. Further multicentric studies with wider recruitment of patients should be performed to confirm our findings, potentially leading to changes in the recommended treatment for carefully monitored at-risk patients.https://www.mdpi.com/2072-6694/13/19/4928melanomaadverse eventsimmunotherapy |
| spellingShingle | Jean-Matthieu L’Orphelin Emilie Varey Amir Khammari Brigitte Dreno Anne Dompmartin Severe Late-Onset Grade III-IV Adverse Events under Immunotherapy: A Retrospective Study of 79 Cases Cancers melanoma adverse events immunotherapy |
| title | Severe Late-Onset Grade III-IV Adverse Events under Immunotherapy: A Retrospective Study of 79 Cases |
| title_full | Severe Late-Onset Grade III-IV Adverse Events under Immunotherapy: A Retrospective Study of 79 Cases |
| title_fullStr | Severe Late-Onset Grade III-IV Adverse Events under Immunotherapy: A Retrospective Study of 79 Cases |
| title_full_unstemmed | Severe Late-Onset Grade III-IV Adverse Events under Immunotherapy: A Retrospective Study of 79 Cases |
| title_short | Severe Late-Onset Grade III-IV Adverse Events under Immunotherapy: A Retrospective Study of 79 Cases |
| title_sort | severe late onset grade iii iv adverse events under immunotherapy a retrospective study of 79 cases |
| topic | melanoma adverse events immunotherapy |
| url | https://www.mdpi.com/2072-6694/13/19/4928 |
| work_keys_str_mv | AT jeanmatthieulorphelin severelateonsetgradeiiiivadverseeventsunderimmunotherapyaretrospectivestudyof79cases AT emilievarey severelateonsetgradeiiiivadverseeventsunderimmunotherapyaretrospectivestudyof79cases AT amirkhammari severelateonsetgradeiiiivadverseeventsunderimmunotherapyaretrospectivestudyof79cases AT brigittedreno severelateonsetgradeiiiivadverseeventsunderimmunotherapyaretrospectivestudyof79cases AT annedompmartin severelateonsetgradeiiiivadverseeventsunderimmunotherapyaretrospectivestudyof79cases |