Review of the Diagnosis, Treatment, and Outcomes of Immunotherapy-Associated Autoimmune Hemolytic Anemia

Michaela Hayes; Carol A. Carman

doi:10.29074/ascls.2025003286

Article Figures & Data

Figures

Tables

Download figure
Open in new tab
Download powerpoint
Figure 1.
Summary of case reports database search flowchart.
Download figure
Open in new tab
Download powerpoint
Figure 2.
Recommended diagnostic and treatment flowchart.

Tables

Figures

View popup

Table 1.

Summary diagnosis, treatment, and outcomes of case reports

Reference	Case #	ICI	# of Doses Before Symptoms	Autoimmune/Predisposition^{^a}	Treatment	Hgb Recovery^{^b}	Other irAE	ICI Restarted	Diagnosis^{^c}
Algaze et al¹⁹	1	Nivolumab	21	CLL	Methylprednisolone, prednisone, and folic acid	Complete	None Reported	Yes/no recurrence	No^{^d}
Chambers et al²⁹	1	Atezolizumab	29	None reported	Prednisone	Unknown	No	No	Yes
Dirven et al¹⁸	1	Nivolumab	1	CLL	Methylprednisolone	Complete	None reported	No	Yes
Dirven et al¹⁸	2	Nivolumab	3	CLL	Dexamethasone	Complete	Yes	No	Yes
Dutertre et al¹⁶	1	Atezolizumab	1	Yes	Methylprednisolone, prednisone, and rituximab	Unknown	None reported	Unknown	Yes
Fetter et al⁵	1	Nivolumab and ipilimumab	4	None reported	Prednisone	Complete	Yes	Yes^{^e}/recurrence	Yes
Fetter et al⁵	2	Pembrolizumab	2	None reported	Prednisone	Partial	Yes	No	Yes
Fukushima et al³⁰	1	Atezolizumab	3	No	Prednisone	Partial	Yes	No	Yes
Hasanov et al²³	1	Nivolumab	7	None reported	Prednisone and rituximab	Unknown	None reported	No	Yes
Jobson et al²⁰	1	Ipilimumab	2	CLL	Methylprednisolone, intravenous immune globulin, cyclophosphamide, and splenectomy	Complete	None reported	Yes/no recurrence	Yes^{^f}
Johnstone and Khan³¹	1	Pembrolizumab	13	None reported	Prednisone and folic acid	Complete	Yes	No	Yes
Khan et al¹⁴	1	Nivolumab and ipilimumab	2	Yes	Methylprednisolone & rituximab	Complete	None reported	Yes/recurrence	Yes
Khosla et al⁹	1	Atezolizumab	NR	None reported	Prednisone	Complete	None reported	No	Yes
Kong et al¹³	1	Nivolumab	5	Yes	Prednisone	Complete	None reported	No	Yes^{^g}
Ogawa et al²⁴	1	Pembrolizumab	1	None reported	Prednisone	No^{^h}	None reported	No	Yes^{^g}
Okawa et al³²	1	Pembrolizumab	1	None reported	Prednisone	Partial	Yes	Unknown	Yes
Olson et al³³	1	Nivolumab and ipilimumab	4	None reported	Prednisone and cyclosporine A	Complete	Yes	No	Yes
Ramos and Rovere²²	1	Ipilimumab	20	None reported	Prednisone	Unknown	No	Unknown	Yes
Robilliard et al³⁴	1	Pembrolizumab	4	No	Prednisone	Unknown	Yes	No	Yes
Shaikh et al³⁵	1	Nivolumab	39	None reported	Prednisone, vitamin B12, erythropoietin, and rituximab	Complete	None reported	No	Yes
Sun et al¹⁰	1	Pembrolizumab	1	None reported	Methylprednisolone and prednisone	Complete	None reported	Yes/no recurrence	Yes
	2	Pembrolizumab	1	None reported	Prednisone	Complete	Yes	Unknown	Yes
	3	Nivolumab and ipilimumab	2	None reported	Prednisone and intravenous immune globulin	Unknown	Yes	No	Yes
Tanios et al⁴	1	Nivolumab	24	None reported	Methylprednisolone	No^ⁱ	None reported	No	Yes
Tao et al²⁷	1	Penpulimab	2	None reported	Prednisone, intravenous immune globulin, and plasmapheresis	Partial	None reported	No	No
Tardy et al³⁶	1	Nivolumab	2	None reported	Prednisone	Partial	None reported	Yes/no recurrence	Yes
Williams and Aitchison³⁷	1	Pembrolizumab	34	None reported	Methylprednisolone	Complete	Yes	No	Yes
Younce et al²⁸	1	Atezolizumab	1	None reported	Prednisone, folic acid, darbepoetin, and iron sucrose	Partial	None reported	Yes/no recurrence	Yes
Yun et al⁸	1	Pembrolizumab	3	CLL	Prednisone, rituximab, and ibrutinib	Complete	None reported	No	Yes^{^f}
Zhang et al¹⁵	1	Pembrolizumab	1	Yes	Methylprednisolone and prednisone	Unknown	Yes	No	Yes

Note. AIHA, autoimmune hemolytic anemia; CLL, chronic lymphocytic leukemia; Hgb, hemoglobin; HLH, hemophagocytic lymphohistiocytosis; ICI, immune checkpoint inhibitor; irAE, immune-related adverse event; ITP, immune thrombocytopenic purpura.

↵a History of autoimmune/predisposition to developing.
↵b Complete hemoglobin recovery is defined as 0.0–1.0 g/dL relative to pretreatment hemoglobin, while partial hemoglobin recovery is characterized as 1.1–2.0 g/dL relative to pretreatment hemoglobin. Unknown recovery is recorded when data are missing, making interpretation impossible.
↵c The treating physician considers ICI the most likely etiology of AIHA.
↵d Physician was unable to exclude other possible causes of AIHA.
↵e This patient was rechallenged with 3 doses of pembrolizumab after developing nivolumab and ipilimumab–associated AIHA.
↵f Patient was diagnosed with exacerbated T-cell dysfunction in CLL causing AIHA.
↵g Patient was diagnosed with exacerbation of preexisting AIHA induced by ICI treatment.
↵h Patient died of other causes before recovery.
↵i Patient died because of bradycardia and cardiac arrest caused by anemia with a hemoglobin of 3 g/dL.