Highlights
- •Haematological immune-related adverse events are rare and initially asymptomatic.
- •Anaemia, thrombocytopenia and neutropenia comprised ~1/3 of cases each.
- •Regular blood count and prompt management are crucial as hem-irAE can be fatal.
- •Management may require immunosuppression beyond corticosteroids.
Abstract
Introduction
With the increasing use of checkpoint inhibitors, rare immune-related adverse events
(irAE) are being identified. Haematological irAE (hem-irAE) are difficult to treat
and have shown high mortality rates. In order to improve side-effect management for
these potentially life-threatening events, we analysed frequency, severity and outcomes.
Patients and methods
Patients who developed hem-irAE while being treated with immune checkpoint inhibitors
(ICI) therapy were retrospectively identified from 18 international cancer centres.
Results
In total, more than 7626 patients treated with ICI were screened, and 50 patients
with hem-irAE identified. The calculated incidence amounts to 0.6% and median onset
was 6 weeks after the ICI initiation (range 1–128 weeks). Thrombocytopenia and leucopaenia
were the most frequent hem-irAE with 34% (17/50) and 34% (17/50), respectively, followed
by anaemia 28% (14/50), hemophagocytic lymphohistiocytosis (4% (2/50)), aplastic anaemia
(2% (1/50)), acquired haemophilia A (2% (1/50)) and coagulation deficiency (2% (1/50)).
Simultaneous thrombocytopenia and neutropenia occurred in two patients, concurrent
anaemia and thrombocytopenia in one patient. Other than cessation of ICI (in 60%)
and corticosteroids (in 78%), treatment included second-line immunosuppression in
24% of cases. Events resolved in 78% (39/50), while 18% (9/50) had persistent changes,
and 2% (1/50) had fatal outcomes (agranulocytosis).
Conclusion
Hem-irAE can affect all haematopoietic blood cell lineages and may persist or even
be fatal. Management may require immunosuppression beyond corticosteroids. Although
these irAE are rare, treating physicians should be aware, monitor blood counts regularly
and promptly act upon detection.
Keywords
Abbreviations:
AIHA (autoimmune haemolytic anaemia), ATG (anti-thymocyte globulin), CTCAE (Common Terminology Criteria of Adverse Events), CTLA-4 (anti-cytotoxic-T-lymphocyte antigen 4), CyA (cyclosporine A), FEIBA (Factor VIII inhibitor bypassing agent), FFP (fresh frozen plasma), G-CSF (granulocyte-colony-stimulating factor), hem-irAE (haematological immune-related adverse event), HLH (hemophagocytic lymphohistiocytosis), ICI (immune checkpoint inhibitors), irAE (immune-related adverse event), IVIG (intravenous immunoglobulin), MMF (mycophenolate mofetil), PD1 (programmed cell death-1), PRBC (packed red blood cells), RTX (rituximab), SERIO (Side Effect Registry Immuno-Oncology)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: March 08, 2021
Accepted:
January 12,
2021
Received in revised form:
December 9,
2020
Received:
October 22,
2020
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
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- Response to letter entitled: ‘Re: Hematological immune related adverse events after treatment with immune checkpoint inhibitors’European Journal of CancerVol. 153
- PreviewCheckpoint inhibitor–induced haemophagocytic histiocytosis (HLH) is an important side-effect with a challenging therapy and high mortality rate. Thus, we agree that it is critical to raise awareness to the condition, which allows early detection and treatment. It is also essential to gather data on these events to establish best practice. Case reports are an important tool to identify signals for further investigation of such rare events as has been the case for cardiomyositis [1], which triggered an US Food and Drug Administration (FDA) initiative.
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- Re: Hematological immune related adverse events after treatment with immune checkpoint inhibitors: Immune checkpoint inhibitor–related haemophagocytic lymphohistiocytosisEuropean Journal of CancerVol. 153
- PreviewWe read with great interest the article by Kramer et al. [1] on the haematological adverse effects associated with immune checkpoint inhibitors (ICIs). The authors have extensively discussed several rare but clinically significant hematological adverse effects that may also prove to be fatal in some cases. The adverse effect that drew our attention, in particular, is haemophagocytic lymphohistiocytosis (HLH). HLH is a potentially fatal clinical syndrome that results from a severe, uncontrolled hyperinflammatory state, which may be triggered by several causes such as infection, malignancy, drugs and so on [2].
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