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

Rebecca Karp Leaf, Christopher Ferreri, Deepa Rangachari, James Mier, Wesley Witteles, George Ansstas, Theodora Anagnostou, Leyre Zubiri, Zofia Piotrowska, Thein H. Oo, David Iberri, Mark Yarchoan, April K.S. Salama, Douglas B. Johnson, Andrew D. Leavitt, Osama E. Rahma, Kerry L. Reynolds, David E. Leaf

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalAmerican journal of hematology
DOIs
StatePublished - Jan 1 2019

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Autoimmune Hemolytic Anemia
Coombs Test
Glucocorticoids
Hemoglobins
Preexisting Condition Coverage
Lymphoproliferative Disorders
Therapeutics
Immunosuppressive Agents
Recurrence

ASJC Scopus subject areas

  • Hematology

Cite this

Clinical and laboratory features of autoimmune hemolytic anemia associated with immune checkpoint inhibitors. / Leaf, Rebecca Karp; Ferreri, Christopher; Rangachari, Deepa; Mier, James; Witteles, Wesley; Ansstas, George; Anagnostou, Theodora; Zubiri, Leyre; Piotrowska, Zofia; Oo, Thein H.; Iberri, David; Yarchoan, Mark; Salama, April K.S.; Johnson, Douglas B.; Leavitt, Andrew D.; Rahma, Osama E.; Reynolds, Kerry L.; Leaf, David E.

In: American journal of hematology, 01.01.2019.

Research output: Contribution to journalArticle

Leaf, RK, Ferreri, C, Rangachari, D, Mier, J, Witteles, W, Ansstas, G, Anagnostou, T, Zubiri, L, Piotrowska, Z, Oo, TH, Iberri, D, Yarchoan, M, Salama, AKS, Johnson, DB, Leavitt, AD, Rahma, OE, Reynolds, KL & Leaf, DE 2019, 'Clinical and laboratory features of autoimmune hemolytic anemia associated with immune checkpoint inhibitors', American journal of hematology. https://doi.org/10.1002/ajh.25448
Leaf, Rebecca Karp ; Ferreri, Christopher ; Rangachari, Deepa ; Mier, James ; Witteles, Wesley ; Ansstas, George ; Anagnostou, Theodora ; Zubiri, Leyre ; Piotrowska, Zofia ; Oo, Thein H. ; Iberri, David ; Yarchoan, Mark ; Salama, April K.S. ; Johnson, Douglas B. ; Leavitt, Andrew D. ; Rahma, Osama E. ; Reynolds, Kerry L. ; Leaf, David E. / Clinical and laboratory features of autoimmune hemolytic anemia associated with immune checkpoint inhibitors. In: American journal of hematology. 2019.
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AU - Witteles, Wesley

AU - Ansstas, George

AU - Anagnostou, Theodora

AU - Zubiri, Leyre

AU - Piotrowska, Zofia

AU - Oo, Thein H.

AU - Iberri, David

AU - Yarchoan, Mark

AU - Salama, April K.S.

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AU - Reynolds, Kerry L.

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