A case of autoimmune haemolytic anaemia after 39 cycles of nivolumab

Shaikh, Hira; Daboul, Nour; Albrethsen, Mary; Fazal, Salman

doi:10.1136/bcr-2018-224608

Cited by 14 publications

(10 citation statements)

References 19 publications

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“…Early B-cell changes correlated with a higher rate of grade 3 or higher irAEs 6 months after starting treatment. Contrastingly, several groups have shown through case report series' that B-cell depletion therapy using Rituximab successfully treated B-cell-mediated irAEs in NSCLC [97,98], SCLC [99], Melanoma [100] and Urothelial Carinoma [101]. This recapitulates the idea of B-cell enumeration and selective targeting of certain microenvironmental B-cell populations.…”

Section: The Interplay Of B Cells and Checkpoint Blockadementioning

confidence: 79%

The role of B lymphocytes in the immuno-biology of non-small-cell lung cancer

Patel

Richter

Drayson

et al. 2020

Cancer Immunol Immunother

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Tumour-infiltrating immune cells have been widely implicated to play a significant role in carcinogenesis, through both pro-or anti-tumour effects. The multi-faceted effects of lung cancer associated T lymphocytes have been extensively studied, and yet, the role of B lymphocytes remains an area less studied. In this review, we will describe the current understanding of the role of tumour-infiltrating B lymphocytes in NSCLC, discuss their prognostic significance, their functionality within the tumour microenvironment and ultimately how we might harness B-cell biology to develop B-cell therapeutic strategies in cancer.

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Section: The Interplay Of B Cells and Checkpoint Blockadementioning

confidence: 79%

The role of B lymphocytes in the immuno-biology of non-small-cell lung cancer

Patel

Richter

Drayson

et al. 2020

Cancer Immunol Immunother

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“…We identified 17 published cases of ICPi‐AIHA . The clinical and laboratory features of ICPi‐AIHA in these 17 cases are summarized in Supporting Information Table S3.…”

Section: Resultsmentioning

confidence: 99%

Clinical and laboratory features of autoimmune hemolytic anemia associated with immune checkpoint inhibitors

et al. 2019

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Immune checkpoint inhibitors (ICPis) are a novel class of immunotherapeutic agents that have revolutionized the treatment of cancer; however, these drugs can also cause a unique spectrum of autoimmune toxicity. Autoimmune hemolytic anemia (AIHA) is a rare, but often severe, complication of ICPis. We identified 14 patients from nine institutions across the United States who developed ICPi-AIHA. The median interval from ICPi initiation to development of AIHA was 55 days (interquartile range [IQR], 22-110 days). Results from the direct antiglobulin test (DAT) were available for 13 of 14 patients: 8 patients (62%) had a positive DAT and 5 (38%) had a negative DAT. The median pretreatment and nadir hemoglobin concentrations were 11.8 g/dL (IQR, 10.2-12.9 g/dL) and 6.3 g/dL (IQR, 6.1-8.0 g/dL), respectively. Four patients (29%) had a preexisting lymphoproliferative disorder, and two (14%) had a positive DAT prior to initiation of ICPi therapy. All patients were treated with glucocorticoids, with three requiring additional immunosuppressive therapy. Complete and partial recoveries of hemoglobin were achieved in 12 (86%) and 2 (14%) patients, respectively. Seven patients (50%) were rechallenged with ICPis, and one (14%) developed recurrent AIHA. Clinical and laboratory features of ICPi-AIHA were similar in DAT positive and negative patients. ICPi-AIHA shares many clinical features with primary AIHA; however, a unique aspect of ICPi-AIHA is a high incidence of DAT negativity. Glucocorticoids are an effective first-line treatment in the majority of patients with ICPi-AIHA, and most patients who are rechallenged with an ICPi do not appear to develop recurrence of AIHA. a Long-standing history of leukopenia of unclear etiology, bone marrow biopsy negative for malignancy, and leukopenia believed to be autoimmune in nature. b Received indoximod in combination with ICPi therapy as part of a clinical trial. c R-CHOP, fludarabine (received >3 years prior to development of AIHA), XRT, auto-SCT for treatment of MZL, and cisplatin and etoposide for treatment of NSCLC. d Received nivolumab on a clinical trial after conventional chemotherapy. e 5-FU, oxaliplatin, irinotecan, bevacizumab, panitumumab, regorafenib, and trifluridine/tipiracil. f Received GVAX and cyclophosphamide in combination with ICPi therapy as part of a clinical trial. g Dabrafenib, trametinib for treatment of melanoma, fludarabine (received >3 years prior to development of AIHA), cyclophosphamide, bendamustine, rituximab, obinutuzumab, and ibrutinib for treatment of CLL.

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“…Treatment of this condition should include corticosteroids (methylprednisolone 1-2 mg/kg). Furthermore, administration of rituximab has also been reported [80]. Although its use has not been described in the literature as it is a rare entity, cyclosporine, mycophenolate, cyclophosphamide, azathioprine or intravenous immunoglobulins may be considered for severe situations [17].…”

Section: Autoimmune Haemolytic Anaemiamentioning

confidence: 99%

Safety and Tolerability of Immune Checkpoint Inhibitors (PD-1 and PD-L1) in Cancer

et al. 2019

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Immunotherapy has emerged in recent years and has revolutionized the treatment of cancer. Immune checkpoint inhibitors, including anti-cytotoxic T lymphocyte antigen-4 (CTLA-4), anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) agents, are the first of this new generation of treatments. Anti-PD-1/PD-L1 agents target immune cells by blocking the PD-1/PD-L1 pathway. This blockade leads to enhancement of the immune system and therefore restores the tumour-induced immune deficiency selectively in the tumour microenvironment. However, this shift in the balance of the immune system can also produce adverse effects that involve multiple organs. The pattern of toxicity is different from traditional chemotherapy agents or targeted therapy, and there is still little experience in recognizing and managing it. Thus, toxicity constitutes a real clinical management challenge and any new alteration should be suspected of being treatmentrelated. The most common toxicities occur in the skin, gastrointestinal tract, lungs, and endocrine, musculoskeletal, renal, nervous, haematologic, cardiovascular and ocular systems. Immune-mediated toxic effects are usually manageable, but toxicities may sometimes lead to treatment withdrawal, and even fulminant and fatal events can occur. Oncologists need to collaborate with internists, clinical immunologists and other specialists to understand, manage and prevent toxicity derived from immunotherapy. This review focuses on the mechanisms of toxicity of anti-PD-1/PD-L1 agents, and its diagnosis and management.

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A case of autoimmune haemolytic anaemia after 39 cycles of nivolumab

Cited by 14 publications

References 19 publications

The role of B lymphocytes in the immuno-biology of non-small-cell lung cancer

The role of B lymphocytes in the immuno-biology of non-small-cell lung cancer

Clinical and laboratory features of autoimmune hemolytic anemia associated with immune checkpoint inhibitors

Safety and Tolerability of Immune Checkpoint Inhibitors (PD-1 and PD-L1) in Cancer

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