Thrombocytopenia in patients with melanoma receiving immune checkpoint inhibitor therapy View Full Text


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Article Info

DATE

2017-02-21

AUTHORS

Eileen Shiuan, Kathryn E. Beckermann, Alpaslan Ozgun, Ciara Kelly, Meredith McKean, Jennifer McQuade, Mary Ann Thompson, Igor Puzanov, John P. Greer, Suthee Rapisuwon, Michael Postow, Michael A. Davies, Zeynep Eroglu, Douglas Johnson

ABSTRACT

BackgroundImmune 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 presentationsA 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.ConclusionsThrombocytopenia, 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. More... »

PAGES

8

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s40425-017-0210-0

DOI

http://dx.doi.org/10.1186/s40425-017-0210-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1083870665

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28239462


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21 schema:description BackgroundImmune 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 presentationsA 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.ConclusionsThrombocytopenia, 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.
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28 BackgroundImmune checkpoint inhibitors
29 ConclusionsThrombocytopenia
30 Herein
31 Immune
32 PD-1 inhibition
33 T-lymphocyte antigen-4
34 addition
35 additional steroids
36 adverse events
37 algorithm
38 anti-PD-1 monotherapy
39 antibodies
40 antigen-4
41 biopsy
42 bleeding
43 bone marrow biopsy
44 cancer
45 cases
46 chart review
47 checkpoint inhibition
48 checkpoint inhibitor therapy
49 checkpoint inhibitors
50 colitis
51 combination
52 corticosteroid regimens
53 count
54 days
55 death-1
56 dermatitis
57 diagnosis
58 discontinuation
59 events
60 females
61 first patient
62 frequency
63 frequent event
64 hemorrhage
65 idiopathic thrombocytopenic purpura
66 immune checkpoint inhibition
67 immune checkpoint inhibitor therapy
68 immune checkpoint inhibitors
69 immunoglobulin
70 incidence
71 inhibition
72 inhibitor therapy
73 inhibitors
74 intracranial hemorrhage
75 intravenous immunoglobulin
76 irAE
77 lack
78 large number
79 less frequent events
80 majority
81 majority of patients
82 marrow biopsy
83 melanoma
84 mild cases
85 mild thrombocytopenia
86 monotherapy
87 mucosal bleeding
88 number
89 observations
90 patients
91 petechiae
92 platelet count
93 pneumonitis
94 positive melanoma
95 prednisone
96 purpura
97 rechallenge
98 recovery
99 regimens
100 resolution
101 response
102 retrospective chart review
103 review
104 rituximab
105 second patient
106 series
107 severe cases
108 severe idiopathic thrombocytopenic purpura
109 spectra
110 spontaneous resolution
111 stabilization
112 standard therapy
113 steroid treatment
114 steroids
115 therapy
116 thrombocytopenia
117 thrombocytopenic purpura
118 treatment
119 treatment algorithm
120 treatment of cancer
121 treatment of prednisone
122 treatment response
123 weeks
124 wild-type melanoma
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