Clinical diagnosis and treatment recommendations for immune checkpoint inhibitor‐related hematological adverse events

Zhuang, Junling; Du, Jianhua; Guo, Xiaoxiao; Zhou, Jiaxin; Duan, Lian; Qiu, Wei; Si, Xiaoyan; Zhang, Li; Li, Yue; Liu, Xiaowei; Wang, Hanping; Zhou, Daobin

doi:10.1111/1759-7714.13281

Cited by 31 publications

(24 citation statements)

References 32 publications

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“…In a meta-analysis of 9324 patients, the frequency of neutropenia was smaller than 1%. 88 Previously reported reactivation of viral infections (ie, cytomegalovirus, hepatitis B) under ICI therapy were mostly observed following immunosuppressive treatment of irAEs. Hence, it does not appear reasonable to assume that patients undergoing ICI are at higher risk of becoming infected by SARS-COV-2 or other infectious agents compared with patients without ICI treatment.…”

Section: Covid-19mentioning

confidence: 99%

On the use of immune checkpoint inhibitors in patients with viral infections including COVID-19

Gambichler

Reuther

Scheel

et al. 2020

J Immunother Cancer

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The present review summarizes up-to-date evidence addressing the frequently discussed clinical controversies regarding the use of immune checkpoint inhibitors (ICIs) in cancer patients with viral infections, including AIDS, hepatitis B and C, progressive multifocal leukoencephalopathy, influenza, and COVID-19. In detail, we provide available information on (1) safety regarding the risk of new infections, (2) effects on the outcome of pre-existing infections, (3) whether immunosuppressive drugs used to treat ICI-related adverse events affect the risk of infection or virulence of pre-existing infections, (4) whether the use of vaccines in ICI-treated patients is considered safe, and (5) whether there are beneficial effects of ICIs that even qualify them as a therapeutic approach for these viral infections.

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Section: Covid-19mentioning

confidence: 99%

On the use of immune checkpoint inhibitors in patients with viral infections including COVID-19

Gambichler

Reuther

Scheel

et al. 2020

J Immunother Cancer

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“…Of note, the accurate mechanism of TRAEs occurrence during this treatment (anti-angiogenesis-related or immune-related) can differ owing to individual differences. For instance, both drugs may lead to thrombocytopenia, which may be a consequence of anti-angiogenic agent-induced thrombotic microangiopathy and atypical hemolytic uremic syndrome or ICIs-induced overactivation of T cells ( 165 – 167 ). According to those reports, the treatment-related thrombocytopenia diminished with the discontinuation of agents or intravenous monoclonal antibodies (e.g., eculizumab) from the perspective of anti-angiogenesis therapy, or with the application of corticosteroids or immunosuppressive drugs from the perspective of ICIs therapy.…”

Section: Safety Of Combination Therapy Of Anti-angiogenic Agents Andmentioning

confidence: 99%

Anti-angiogenic Agents in Combination With Immune Checkpoint Inhibitors: A Promising Strategy for Cancer Treatment

et al. 2020

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Advances in cancer immunity have promoted a major breakthrough in the field of cancer therapy. This is mainly associated with the successful development of immune checkpoint inhibitors (ICIs) for multiple types of human tumors. Blockade with different ICIs, including programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, may activate the immune system of the host against malignant cells. However, only a subgroup of patients with cancer would benefit from immune checkpoint blockade. Some patients experience primary resistance to initial immunotherapy, and a majority eventually develop acquired resistance to ICIs. However, the mechanisms involved in the development of drug resistance to immune checkpoint blockade remain unclear. Recent studies supported that combination of ICIs and anti-angiogenic agents could be a promising therapeutic strategy for overcoming the low efficacy of ICIs. Moreover, through their direct anti-cancer effect by inhibiting tumor growth and metastasis, anti-angiogenic drugs reprogram the tumor milieu from an immunosuppressive to an immune permissive microenvironment. Activated immunity by immune checkpoint blockade also facilitates anti-angiogenesis by downregulating the expression of vascular endothelial growth factor and alleviating hypoxia condition. Many clinical trials showed an improved anti-cancer efficacy and prolonged survival following the addition of anti-angiogenic agents to ICIs. This review summarizes the current understanding and clinical development of combination therapy with immune checkpoint blockade and anti-angiogenic strategy.

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“…On the whole, a higher incidence has been reported with CTLA-4 inhibitors (i.e., ipilimumab) versus PD-1 inhibitors (i.e., pembrolizumab and nivolumab) and their association increased the risk. At variance, hematologic adverse events seem more frequent after PD-1 inhibitors and are mainly unilineage cytopenia, or bilineage cytopenia, whilst AH, TTP, eosinophilia, LGL, and hemophagocytic lymphohistiocytosis are rare [ 106 , 107 ]. A meta-analysis of 9324 patients indicated that the incidence of anemia, thrombocytopenia, and neutropenia was 9.8%, 2.8%, and 0.94%, respectively [ 106 ], with AIHA possibly having a fulminant course.…”

Section: Autoimmune Complications Associated With Old and New Antimentioning

confidence: 99%

Autoimmune Complications in Hematologic Neoplasms

Barcellini

Giannotta

Fattizzo

2021

Cancers

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Autoimmune cytopenias (AICy) and autoimmune diseases (AID) can complicate both lymphoid and myeloid neoplasms, and often represent a diagnostic and therapeutic challenge. While autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) are well known, other rarer AICy (autoimmune neutropenia, aplastic anemia, and pure red cell aplasia) and AID (systemic lupus erythematosus, rheumatoid arthritis, vasculitis, thyroiditis, and others) are poorly recognized. This review analyses the available literature of the last 30 years regarding the occurrence of AICy/AID in different onco-hematologic conditions. The latter include chronic lymphocytic leukemia (CLL), lymphomas, multiple myeloma, myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), myeloproliferative neoplasms, and acute leukemias. On the whole, AICy are observed in up to 10% of CLL and with higher frequencies in certain subtypes of non-Hodgkin lymphoma, whilst they occur in less than 1% of low-risk MDS and CMML. AID are described in up to 30% of myeloid and lymphoid patients, including immune-mediated hemostatic disorders (acquired hemophilia, thrombotic thrombocytopenic purpura, and anti-phospholipid syndrome) that may be severe and fatal. Additionally, AICy/AID are found in about 10% of patients receiving hematopoietic stem cell transplant or treatment with new checkpoint inhibitors. Besides the diagnostic difficulties, these AICy/AID may complicate the clinical management of already immunocompromised patients.

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Clinical diagnosis and treatment recommendations for immune checkpoint inhibitor‐related hematological adverse events

Cited by 31 publications

References 32 publications

On the use of immune checkpoint inhibitors in patients with viral infections including COVID-19

On the use of immune checkpoint inhibitors in patients with viral infections including COVID-19

Anti-angiogenic Agents in Combination With Immune Checkpoint Inhibitors: A Promising Strategy for Cancer Treatment

Autoimmune Complications in Hematologic Neoplasms

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