Haematological immune-related adverse events with immune checkpoint inhibitors, how to manage?

Michot, Jean‐Marie; Lazarovici, Julien; Tieu, Ashley; Champiat, Stéphane; Voisin, Anne-Laure; Ebbo, Mikaël; Godeau, Bertrand; Michel, Marc; Ribrag, Vincent; Lambotte, Olivier

doi:10.1016/j.ejca.2019.07.014

Cited by 113 publications

(160 citation statements)

References 97 publications

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“…Regardless of cancer type, ICI-related CRS safety reports were more numerous on anti-PD-1/PD-L1 antibodies, in line with the single case reports of CRS developed on either nivolumab or pembrolizumab (Foran et al, 2017;Rassy et al, 2017;Rotz et al, 2017;Zhao et al, 2018;Dimitriou et al, 2019;Honjo et al, 2019;Kogure et al, 2019;Oda et al, 2019). Moreover, a recent review of the largest clinical trials of ICIs (Michot et al, 2019), found that the frequency of hematological irAEs of all grades (including CRS), was higher with anti-PD-1 (4.1%) and anti-PD-L1 (4.7%) than with anti-CTLA-4 agents (0.5%, P < 0.0001). However, our finding might also reflect a more widespread use of anti-PD-1/ PD-L1 agents in clinical practice as compared to anti-CTLA-4 (Khoja et al, 2017).…”

Section: Discussionmentioning

confidence: 57%

Immune Checkpoint Inhibitor-Related Cytokine Release Syndrome: Analysis of WHO Global Pharmacovigilance Database

et al. 2020

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Immune checkpoint inhibitors (ICIs) have proven effective in the treatment of numerous cancers; however, they have been associated with immune-related adverse events (irAEs), among which cytokine release syndrome (CRS) has been reported in a few case reports. To describe the burden of ICI-related CRS and raise awareness of CRS as irAE, we queried VigiBase, the World Health Organization global database of spontaneously reported suspected adverse drug reactions (ADRs), and retrieved safety reports of suspected CRS associated with ICIs, gathered in the database through January 12 th 2020. We assessed ICI-related CRS safety reports in terms of geographical and temporal patterns of reporting, patient demographics and clinical features, treatment characteristics, CRS clinical presentation, timing, seriousness, and outcome. We retrieved 58 cases of whom 43 (74%) reported CRS with anti-programmed death-1/antiprogrammed death-ligand 1 agents. Melanoma (n=17, 29%) and hematologic malignancies (n=16, 28%) were the most common underlying cancers. ICIs were the solely suspected drugs in 37 (64%) cases. Typical signs and symptoms of CRS were reported in 25 (43%) patients. ICI-related CRS developed a median of 4 weeks after ICI initiation (IQR 1-18 weeks, n=9, 16%). Besides two fatal cases, CRS recovered/was recovering at the time of reporting in 35 (60%) cases. We observed differences in the geographical pattern of ICI-related CRS reporting, with a high proportion of ICI-related CRS cases in Australia and North America (0.14 and 0.10% respectively). Due to ICI expanding indications, clinicians should be aware that ICIs could contribute to CRS onset in cancer patients as pharmacological triggers.

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Section: Discussionmentioning

confidence: 57%

Immune Checkpoint Inhibitor-Related Cytokine Release Syndrome: Analysis of WHO Global Pharmacovigilance Database

et al. 2020

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“…In a review of 19 large clinical trials of ICIs, such as anti-PD-L1, anti-PD-1, and anti-cytotoxic T-lymphocyte-associated antigen 4 antibodies, used for the treatment of melanoma, lung cancer, bladder cancer, etc., the frequency of the occurrence of hematological irAE was estimated to be 3.6% cases for all grades and 0.7% cases for grades3 or 4 14 . ITP was reported to be one of the most frequent type of hematological irAEs [ 13 , 14 ]. To the best of our knowledge, this is the first case report of ITP induced by nivolumab in a patient with MPM.…”

Section: Discussionmentioning

confidence: 99%

Nivolumab-induced immune thrombocytopenia in a patient with malignant pleural mesothelioma

Sakakibara‐Konishi

Sato

et al. 2020

Respiratory Medicine Case Reports

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Malignant pleural mesothelioma (MPM) is a rare and highly aggressive tumor. Nivolumab showed durable antitumor effect in patients with recurrent MPM and was approved for those patients in Japan in 2018. Immune related adverse event (irAE) is occurred in various organs and is suggestive to be related to better outcome of nivolumab. Frequency of hematological irAE is low and there are few reports about hematological irAE and association between irAE and outcome of nivolumab in patients with MPM. We present a case of recurrent MPM who responded to nivolumab treatment and experienced nivolumab-induced immune thrombocytopenia (ITP). Although high dose dexamethasone was administered and platelet count increased transiently, re-administration of dexamethasone was required to maintain normal count of platelet. The careful and intensive management of ITP treatment is necessary in cases who show no response or relapse to initial glucocorticoids treatment. This is the first report about nivolumab-induced ITP and association with response to nivolumab in MPM.

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“…Hematologic irAEs include autoimmune hemolytic anemia, hemolytic uremic syndrome, lymphopenia, thrombocytopenia, plastic anemia, and acquired hemophilia. These adverse events are rare [134,146].…”

Section: Immune-related Adverse Events To Immunotherapymentioning

confidence: 99%

Immunotherapy in the Treatment of Metastatic Melanoma: Current Knowledge and Future Directions

Ralli

Botticelli

Visconti

et al. 2020

Journal of Immunology Research

151

138

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Melanoma is one of the most immunologic malignancies based on its higher prevalence in immune-compromised patients, the evidence of brisk lymphocytic infiltrates in both primary tumors and metastases, the documented recognition of melanoma antigens by tumor-infiltrating T lymphocytes and, most important, evidence that melanoma responds to immunotherapy. The use of immunotherapy in the treatment of metastatic melanoma is a relatively late discovery for this malignancy. Recent studies have shown a significantly higher success rate with combination of immunotherapy and chemotherapy, radiotherapy, or targeted molecular therapy. Immunotherapy is associated to a panel of dysimmune toxicities called immune-related adverse events that can affect one or more organs and may limit its use. Future directions in the treatment of metastatic melanoma include immunotherapy with anti-PD1 antibodies or targeted therapy with BRAF and MEK inhibitors.

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Haematological immune-related adverse events with immune checkpoint inhibitors, how to manage?

Cited by 113 publications

References 97 publications

Immune Checkpoint Inhibitor-Related Cytokine Release Syndrome: Analysis of WHO Global Pharmacovigilance Database

Immune Checkpoint Inhibitor-Related Cytokine Release Syndrome: Analysis of WHO Global Pharmacovigilance Database

Nivolumab-induced immune thrombocytopenia in a patient with malignant pleural mesothelioma

Immunotherapy in the Treatment of Metastatic Melanoma: Current Knowledge and Future Directions

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