Thrombocytopenia in patients with melanoma receiving immune checkpoint inhibitor therapy
Background Immune checkpoint inhibitors, including antibodies against programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), are being used with increasing frequency for the treatment of cancer. Immune-related adverse events (irAEs) including colitis, dermatitis, and pneumonitis ar...
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BMJ Publishing Group
2017-08-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/5/1/8.full |
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| author | Michael Postow Igor Puzanov Suthee Rapisuwon Michael A. Davies Zeynep Eroglu Eileen Shiuan Kathryn E. Beckermann Alpaslan Ozgun Ciara Kelly Meredith McKean Jennifer McQuade Mary Ann Thompson John P. Greer Douglas Johnson |
| author_facet | Michael Postow Igor Puzanov Suthee Rapisuwon Michael A. Davies Zeynep Eroglu Eileen Shiuan Kathryn E. Beckermann Alpaslan Ozgun Ciara Kelly Meredith McKean Jennifer McQuade Mary Ann Thompson John P. Greer Douglas Johnson |
| author_sort | Michael Postow |
| collection | DOAJ |
| description | Background Immune checkpoint inhibitors, including antibodies against programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), are being used with increasing frequency for the treatment of cancer. Immune-related adverse events (irAEs) including colitis, dermatitis, and pneumonitis are well described, but less frequent events are now emerging with larger numbers of patients treated. Herein we describe the incidence and spectrum of thrombocytopenia following immune checkpoint inhibitor therapy and two severe cases of idiopathic thrombocytopenic purpura (ITP).Case presentations A 47-year-old female with recurrent BRAF mutant positive melanoma received combination anti-PD-1 and anti-CTLA-4. Two weeks later, she presented with mucosal bleeding, petechiae, and thrombocytopenia and was treated with standard therapy for ITP with steroids and intravenous immunoglobulin (IVIG). Her diagnosis was confirmed with bone marrow biopsy, and given the lack of treatment response, she was treated with rituximab. She began to have recovery and stabilization of her platelet count that ultimately allowed her to be retreated with PD-1 inhibition with no further thrombocytopenia. A second patient, a 45-year-old female with a BRAF wild-type melanoma, received anti-PD-1 monotherapy and became thrombocytopenic 43 days later. Three weeks of steroid treatment improved her platelet count, but thrombocytopenia recurred and required additional steroids. She later received anti-CTLA-4 monotherapy and developed severe ITP with intracranial hemorrhage. Her ITP resolved after treatment of prednisone, IVIG, and rituximab and discontinuation of checkpoint inhibition. In a retrospective chart review of 2360 patients with melanoma treated with checkpoint inhibitor therapy, <1% experienced thrombocytopenia following immune checkpoint inhibition, and of these, most had spontaneous resolution and did not require treatment.Conclusions Thrombocytopenia, especially ITP, induced by immune checkpoint inhibitors appears to be an uncommon irAE that is manageable with observation in mild cases and/or standard ITP treatment algorithms. In our series, the majority of patients had mild thrombocytopenia that resolved spontaneously or responded to standard corticosteroid regimens. However, in two severe cases, IVIG and rituximab, in addition to steroids, were required. Checkpoint inhibition was resumed successfully in the first patient but rechallenge was not tolerated by the second patient. |
| format | Article |
| id | doaj-art-4aea4b48c5f64a16aded42cd784d24e8 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2017-08-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-4aea4b48c5f64a16aded42cd784d24e82025-08-20T02:13:44ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262017-08-015110.1186/s40425-017-0210-0Thrombocytopenia in patients with melanoma receiving immune checkpoint inhibitor therapyMichael Postow0Igor Puzanov1Suthee Rapisuwon2Michael A. Davies3Zeynep Eroglu4Eileen Shiuan5Kathryn E. Beckermann6Alpaslan Ozgun7Ciara Kelly8Meredith McKean9Jennifer McQuade10Mary Ann Thompson11John P. Greer12Douglas Johnson131Memorial Sloan Kettering Cancer Center, New York, NY, USAAff4 grid.240614.50000000121818635Roswell Park Cancer Institute 14263 Buffalo NY USALombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, District of Columbia, USAMelanoma Medical Onoclogy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA5 H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USAAff1 0000 0004 1936 9916grid.412807.8Medical Scientist Training Program, Vanderbilt University Medical Center 37232 Nashville TN USAAff3 0000 0004 1936 9916grid.412807.8Division of Hematology/OncologyVanderbilt University Medical Center 777 PRB, 2220 Pierce Ave Nashville TN USAAff4 0000 0001 2353 285Xgrid.170693.aDepartment of Cutaneous Oncology, Moffitt Cancer Center and Research Institute 33612 Tampa FL USA4MSKCC, New York, NY, USASarah Cannon Research Institute, Nashville, Tennessee, USAAff7 0000 0001 2291 4776grid.240145.6Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center 77030 Houston TX USAAff11 0000 0004 1936 9916grid.412807.8Department of Pathology, Microbiology, and ImmunologyVanderbilt University Medical Center 37232 Nashville TN USAAff3 0000 0004 1936 9916grid.412807.8Division of Hematology/OncologyVanderbilt University Medical Center 777 PRB, 2220 Pierce Ave Nashville TN USA9 Departments of General Medicine and Infectious Diseases, The Royal Melbourne Hospital, Parkville, Victoria, AustraliaBackground Immune checkpoint inhibitors, including antibodies against programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), are being used with increasing frequency for the treatment of cancer. Immune-related adverse events (irAEs) including colitis, dermatitis, and pneumonitis are well described, but less frequent events are now emerging with larger numbers of patients treated. Herein we describe the incidence and spectrum of thrombocytopenia following immune checkpoint inhibitor therapy and two severe cases of idiopathic thrombocytopenic purpura (ITP).Case presentations A 47-year-old female with recurrent BRAF mutant positive melanoma received combination anti-PD-1 and anti-CTLA-4. Two weeks later, she presented with mucosal bleeding, petechiae, and thrombocytopenia and was treated with standard therapy for ITP with steroids and intravenous immunoglobulin (IVIG). Her diagnosis was confirmed with bone marrow biopsy, and given the lack of treatment response, she was treated with rituximab. She began to have recovery and stabilization of her platelet count that ultimately allowed her to be retreated with PD-1 inhibition with no further thrombocytopenia. A second patient, a 45-year-old female with a BRAF wild-type melanoma, received anti-PD-1 monotherapy and became thrombocytopenic 43 days later. Three weeks of steroid treatment improved her platelet count, but thrombocytopenia recurred and required additional steroids. She later received anti-CTLA-4 monotherapy and developed severe ITP with intracranial hemorrhage. Her ITP resolved after treatment of prednisone, IVIG, and rituximab and discontinuation of checkpoint inhibition. In a retrospective chart review of 2360 patients with melanoma treated with checkpoint inhibitor therapy, <1% experienced thrombocytopenia following immune checkpoint inhibition, and of these, most had spontaneous resolution and did not require treatment.Conclusions Thrombocytopenia, especially ITP, induced by immune checkpoint inhibitors appears to be an uncommon irAE that is manageable with observation in mild cases and/or standard ITP treatment algorithms. In our series, the majority of patients had mild thrombocytopenia that resolved spontaneously or responded to standard corticosteroid regimens. However, in two severe cases, IVIG and rituximab, in addition to steroids, were required. Checkpoint inhibition was resumed successfully in the first patient but rechallenge was not tolerated by the second patient.https://jitc.bmj.com/content/5/1/8.full |
| spellingShingle | Michael Postow Igor Puzanov Suthee Rapisuwon Michael A. Davies Zeynep Eroglu Eileen Shiuan Kathryn E. Beckermann Alpaslan Ozgun Ciara Kelly Meredith McKean Jennifer McQuade Mary Ann Thompson John P. Greer Douglas Johnson Thrombocytopenia in patients with melanoma receiving immune checkpoint inhibitor therapy Journal for ImmunoTherapy of Cancer |
| title | Thrombocytopenia in patients with melanoma receiving immune checkpoint inhibitor therapy |
| title_full | Thrombocytopenia in patients with melanoma receiving immune checkpoint inhibitor therapy |
| title_fullStr | Thrombocytopenia in patients with melanoma receiving immune checkpoint inhibitor therapy |
| title_full_unstemmed | Thrombocytopenia in patients with melanoma receiving immune checkpoint inhibitor therapy |
| title_short | Thrombocytopenia in patients with melanoma receiving immune checkpoint inhibitor therapy |
| title_sort | thrombocytopenia in patients with melanoma receiving immune checkpoint inhibitor therapy |
| url | https://jitc.bmj.com/content/5/1/8.full |
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