PD-1 Blockade in Advanced Melanoma in Patients with Hepatitis C and/or HIV
On the basis of remarkable antitumor activity, programmed death receptor-1 (PD-1) inhibitors pembrolizumab and nivolumab were approved for the treatment of advanced melanoma in the second-line setting following progression on either CTLA-4 inhibitor ipilimumab or BRAF/MEK inhibitors (for BRAF mutate...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Case Reports in Oncological Medicine |
| Online Access: | http://dx.doi.org/10.1155/2015/737389 |
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| _version_ | 1832558654604181504 |
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| author | Diwakar Davar Melissa Wilson Chelsea Pruckner John M. Kirkwood |
| author_facet | Diwakar Davar Melissa Wilson Chelsea Pruckner John M. Kirkwood |
| author_sort | Diwakar Davar |
| collection | DOAJ |
| description | On the basis of remarkable antitumor activity, programmed death receptor-1 (PD-1) inhibitors pembrolizumab and nivolumab were approved for the treatment of advanced melanoma in the second-line setting following progression on either CTLA-4 inhibitor ipilimumab or BRAF/MEK inhibitors (for BRAF mutated melanoma). Given hypothesized risk of triggering exacerbations of autoimmune diseases and/or chronic viral infections, clinical trials (including regulatory studies) evaluating checkpoint blocking antibodies PD-1 and CTLA-4 have excluded patients with autoimmune diseases, chronic hepatitis B/C virus (HBV/HCV), and/or human immunodeficiency virus (HIV) infections. Herein, we describe two patients with advanced melanoma and concomitant HCV/HIV infections treated with PD-1 inhibitor pembrolizumab. Patient 2 with HIV/HCV coinfection progressed after 2 doses of pembrolizumab. Patient 1 who had HCV alone was treated with pembrolizumab with initial partial response. HCV viral load remained stable after 9 cycles of pembrolizumab following which 12-week course of HCV-directed therapy was commenced, resulting in prompt reduction of HCV viral load below detectable levels. Response is ongoing and HCV viral load remains undetectable. In both patients, no significant toxicities were observed when pembrolizumab was initiated. We argue for the further investigation of checkpoint inhibition in cancer patients with underlying chronic viral infections in the context of carefully designed clinical trials. |
| format | Article |
| id | doaj-art-5581e610eef44837b66b97ff93111b37 |
| institution | Kabale University |
| issn | 2090-6706 2090-6714 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Case Reports in Oncological Medicine |
| spelling | doaj-art-5581e610eef44837b66b97ff93111b372025-02-03T01:31:52ZengWileyCase Reports in Oncological Medicine2090-67062090-67142015-01-01201510.1155/2015/737389737389PD-1 Blockade in Advanced Melanoma in Patients with Hepatitis C and/or HIVDiwakar Davar0Melissa Wilson1Chelsea Pruckner2John M. Kirkwood3Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USADivision of Hematology-Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USADivision of Hematology-Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USADivision of Hematology-Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USAOn the basis of remarkable antitumor activity, programmed death receptor-1 (PD-1) inhibitors pembrolizumab and nivolumab were approved for the treatment of advanced melanoma in the second-line setting following progression on either CTLA-4 inhibitor ipilimumab or BRAF/MEK inhibitors (for BRAF mutated melanoma). Given hypothesized risk of triggering exacerbations of autoimmune diseases and/or chronic viral infections, clinical trials (including regulatory studies) evaluating checkpoint blocking antibodies PD-1 and CTLA-4 have excluded patients with autoimmune diseases, chronic hepatitis B/C virus (HBV/HCV), and/or human immunodeficiency virus (HIV) infections. Herein, we describe two patients with advanced melanoma and concomitant HCV/HIV infections treated with PD-1 inhibitor pembrolizumab. Patient 2 with HIV/HCV coinfection progressed after 2 doses of pembrolizumab. Patient 1 who had HCV alone was treated with pembrolizumab with initial partial response. HCV viral load remained stable after 9 cycles of pembrolizumab following which 12-week course of HCV-directed therapy was commenced, resulting in prompt reduction of HCV viral load below detectable levels. Response is ongoing and HCV viral load remains undetectable. In both patients, no significant toxicities were observed when pembrolizumab was initiated. We argue for the further investigation of checkpoint inhibition in cancer patients with underlying chronic viral infections in the context of carefully designed clinical trials.http://dx.doi.org/10.1155/2015/737389 |
| spellingShingle | Diwakar Davar Melissa Wilson Chelsea Pruckner John M. Kirkwood PD-1 Blockade in Advanced Melanoma in Patients with Hepatitis C and/or HIV Case Reports in Oncological Medicine |
| title | PD-1 Blockade in Advanced Melanoma in Patients with Hepatitis C and/or HIV |
| title_full | PD-1 Blockade in Advanced Melanoma in Patients with Hepatitis C and/or HIV |
| title_fullStr | PD-1 Blockade in Advanced Melanoma in Patients with Hepatitis C and/or HIV |
| title_full_unstemmed | PD-1 Blockade in Advanced Melanoma in Patients with Hepatitis C and/or HIV |
| title_short | PD-1 Blockade in Advanced Melanoma in Patients with Hepatitis C and/or HIV |
| title_sort | pd 1 blockade in advanced melanoma in patients with hepatitis c and or hiv |
| url | http://dx.doi.org/10.1155/2015/737389 |
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