Immune-mediated red cell aplasia after anti-CTLA-4 immunotherapy for metastatic melanoma

Gordon, Ilyssa O.; Wade, Takisha; Chin, Kevin M.; Dickstein, Jerome I.; Gajewski, Thomas F.

doi:10.1007/s00262-008-0627-x

Cited by 74 publications

(55 citation statements)

References 8 publications

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“…Hematological toxicities such as anemia, neutropenia, and pancytopenia have been reported in patients treated with ipilimumab [1][2][3], including one case of hemolytic anemia. The patient presented here had no immunological nor hematological toxicities during ipilimumab therapy, but subsequently developed hemolytic anemia within 8 weeks of nivolumab treatment for metastatic melanoma.…”

Section: Discussionmentioning

confidence: 98%

Autoimmune hemolytic anemia induced by anti-PD-1 therapy in metastatic melanoma

et al. 2016

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We report the occurrence of autoimmune hemolytic anemia in a patient receiving the anti-PD-1 monoclonal antibody, nivolumab, for metastatic melanoma in the presence of known red cell alloantibodies, despite having received prior ipilimumab without evidence of hemolysis. The patient had a history of multiple red cell alloantibodies and a positive direct antiglobulin test, identified at the time of a prior transfusion, which occurred before treatment with ipilimumab. The patient developed symptomatic warm autoimmune hemolytic anemia after four cycles of treatment with nivolumab. Clinical improvement was noted following cessation of the drug and treatment with corticosteroids. Given that there was no prior history of hemolysis, even during treatment with ipilimumab, we hypothesize that anti-PD-1 therapy disrupted peripheral tolerance, unmasking an underlying autoimmune predisposition.

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Section: Discussionmentioning

confidence: 98%

Autoimmune hemolytic anemia induced by anti-PD-1 therapy in metastatic melanoma

et al. 2016

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“…Anti-CTLA-4 therapies show remarkable response rates in some subjects, but at the expense of autoimmunity, including autoimmune hypophysitis [10,14,17,18,20,[22][23][24][25][26][27][28][29]. Strategies to limit autoimmunity include development of therapies that limit anti-CTLA-4 therapy to the local, peri-tumoral region.…”

Section: Autoimmunity In Anti-ctla-4 Antibody Trialsmentioning

confidence: 97%

Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: serious immune related adverse events across a spectrum of cancer subtypes

et al. 2009

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Anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) therapies represent a novel approach to cancer treatment via disruption of immune tolerance to antigens located on tumor cells. Disruption of immune tolerance, however, may occur at a cost. A host of immune related adverse events (IRAEs) are associated with anti-CTLA-4 therapy. Autoimmune hypophysitis has been reported in up to 17% of patients with melanoma and renal cell carcinoma treated with this therapy. Familiarity with the spectrum of IRAEs connected to these therapies is paramount for endocrinologists, oncologists and those involved in the care of these subjects. We review here key aspects of diagnosis and treatment of anti-CTLA-4 antibody therapy resultant IRAEs. We describe the first two cases of hypopituitarism in prostate cancer subjects undergoing experimental therapy with ipilimumab. The clinical evidence strongly suggests that the prostate cancer subjects developed autoimmune hypophysitis as a consequence of anti-CTLA-4 treatment. High dose glucocorticoid treatment resulted in markedly improved symptoms, and resolution of focal symptoms and diabetes insipidus. One subject recovered pituitary-thyroid axis function after 9 months; however, both continue to require GC replacement. These cases highlight the importance of early screening and treatment for hypopituitarism in all subjects undergoing treatment with anti-CTLA-4 therapy to prevent a potentially fatal outcome from secondary adrenal insufficiency, a readily treatable disease. We recommend mandatory long term follow-up to monitor the development of other hormonal deficits.

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“…In addition, 2 other publications have reported hematological ipilimumab-induced adverse events. 6,7 The first case reports a patient treated with ipilimumab for metastatic melanoma who had isolated severe neutropenia that was resistant to hematopoietic growth factors and corticotherapy, and resolved after intravenous immunoglobulins. The second case was a man who had a corticoresistant peripheral isolated anemia after treatment with ipilimumab that also evolved favorably after treatment with immunoglobulins.…”

Section: Discussionmentioning

confidence: 99%

Ipilimumab-induced Autoimmune Pancytopenia in a Case of Metastatic Melanoma

Rusquec

Saint‐Jean

Brocard

et al. 2014

Journal of Immunotherapy

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A 77-year-old patient treated with ipilimumab (anti-CTLA-4 antibody) for metastatic melanoma developed autoimmune pancytopenia (anemia, thrombocytopenia, and neutropenia) 8 days after the fourth infusion. This pancytopenia was resistant to high-dose oral corticosteroids (1 mg/kg) and to hematopoietic growth factors. It resolved after intravenous immunoglobulins injection. To date, only 1 case of autoimmune pancytopenia has been reported after this treatment. According to the case that we report, it seems essential to control the leukocyte count before any injection of ipilimumab.

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Immune-mediated red cell aplasia after anti-CTLA-4 immunotherapy for metastatic melanoma

Cited by 74 publications

References 8 publications

Autoimmune hemolytic anemia induced by anti-PD-1 therapy in metastatic melanoma

Autoimmune hemolytic anemia induced by anti-PD-1 therapy in metastatic melanoma

Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: serious immune related adverse events across a spectrum of cancer subtypes

Ipilimumab-induced Autoimmune Pancytopenia in a Case of Metastatic Melanoma

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