Nivolumab-induced cold agglutinin syndrome successfully treated with rituximab

Hasanov, Merve; Konoplev, Sergej; Rojas‐Hernandez, Cristhiam M.

doi:10.1182/bloodadvances.2018019000

Cited by 18 publications

(14 citation statements)

References 17 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: 80%

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: 80%

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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“…Two patients died due to complications of AIHA . We also identified one case of ICPi‐associated cold agglutinin disease, but did not include this patient in our analysis.…”

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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“…9 Occasional cases have been reported following stem cell transplantation and, recently, during therapy with the immune checkpoint-inhibitor nivolumab. 9,74…”

Section: Secondary Casmentioning

confidence: 99%

Novel insights into the treatment of complement-mediated hemolytic anemias

Berentsen

Hill

et al. 2019

Therapeutic Advances in Hematology

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Complement-mediated hemolytic anemias can either be caused by deficiencies in regulatory complement components or by autoimmune pathogenesis that triggers inappropriate complement activation. In paroxysmal nocturnal hemoglobinuria (PNH) hemolysis is entirely complement-driven. Hemolysis is also thought to be complement-dependent in cold agglutinin disease (CAD) and in paroxysmal cold hemoglobinuria (PCH), whereas warm antibody autoimmune hemolytic anemia (wAIHA) is a partially complement-mediated disorder, depending on the subtype of wAIHA and the extent of complement activation. The pathophysiology, clinical presentation, and current therapies for these diseases are reviewed in this article. Novel, complement-directed therapies are being rapidly developed. Therapeutic terminal complement inhibition using eculizumab has revolutionized the therapy and prognosis in PNH but has proved less efficacious in CAD. Upstream complement modulation is currently being investigated and appears to be a highly promising therapy, and two such agents have entered phase II and III trials. Of these, the anti-C1s monoclonal antibody sutimlimab has shown favorable activity in CAD, while the anti-C3 cyclic peptide pegcetacoplan appears to be promising in PNH as well as CAD, and may also have a therapeutic potential in wAIHA.

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Nivolumab-induced cold agglutinin syndrome successfully treated with rituximab

Abstract: Key Points Cold agglutinin syndrome is one of the rare immune-related adverse events of nivolumab. Rituximab should be considered for treatment of nivolumab-induced cold agglutinin syndrome.

Cited by 18 publications

References 17 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

Novel insights into the treatment of complement-mediated hemolytic anemias

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