Table 1.

Summary of recently pubmished cases with neutropenia due to immune checkpoint inhibitors

Authors	Age, Gender	Cancer type	Immune checkpoint inhibitor	No. of cycles before neutropenia	CTCAE (4.03) Grade/ ANC Nadir /mm3	Rheumatological/autoimmune disease or serology	Duration of neutropenia	Bone marrow findings	Associated or preceding irAE	Treatment	Outcome	ICI restarted
Akhtari et al. [9]	42 Female	Melanoma	Ipilimumab	4	G4 ANC - 380	Antineutrophil and platelet autoantibodies.	60 days	Normocellular marrow, myeloid hypoplasia. Second bone marrow: hypocellular; granulocytic hypoplasia and lymphohistiocytic aggregates.	Rash	Pegfilgrastim Prednisone Dexamethasone IVIg, Cyclosporine	Prolonged neutropenia with multiple relapses. Recovery of counts after second course of IVIg. Developed anemia and thrombocytopenia	No
Ban-Hoefen et al. [10]	54 Male	Melanoma	Ipilimumab	4	G4- ANC - 0	No serology	52 days	Hypercellular; increase bland histiocytes, lymphocytosis; near complete absence of granulocyte precursors	Rash	Prednisone IVIG, Cyclosporine Filgrastim, Anti-thymocyte globulin (ATG)	Recovery of counts with ATG/cyclosporine/prednisone combination with filgrastim. Steroids tapered off after 4 months. Normal ANC after 6 months.	No
Tabchi et al. [11]	74 Female	NSCLC	Nivolumab	2	Severe neutropenia likely G-4 (ANC not reported)	Ulcerative colitis in remission	16 days	Absence of myeloid precursors	Hepatitis	Filgrastim, IVIG Prednisone Methylprednisolone	Responded to high dose methylprednisolone.	No
Wozniak et al. [12]	35 Male	Melanoma	Ipilimumab	3	G-4 ANC - 0	No serology	16 days	Granulocytes with features of rejuvenation and preserved maturation; poorly represented erythrocytes.	Rash	Methylprednisolone Filgrastim (both started after 8 days)	Recovery of counts 16 days.	N/A
Barbacki et al. [13]	73 Female	NSCLC	Pembrolizumab	2	G-4 ANC-0	Autoimmune myositis (in remission) Crohn’s disease	12 days	Not performed	None	GCSF, Methylprednisolone, IVIG, Cyclosporine	Recovered counts after 12 days. No recurrence at 3 months	No
Sun et al. [14]	64 Male	Prostate Cancer	Ipilumumab	2	G-3 ANC-770	Weak neutrophil reactive IgM antibodies	14 days	Not performed	None	Methyl prednisone followed by prednisone	Count recovery with no recurrent neutropenia. PSA remained undetectable and patient started lepurolide	No
Meti et al. [15]	59 Male	Melanoma	Ipilimumab/Nivolumab	2	G-4 ANC-0	No serology	16 days	Variable cellularity, hypoplastic granulocytic, unremarkable erythroid and megakaryocytic lineages.	Rash, hepatitis, colitis	Methylprednisolone, IVIG, filgrastim, mycophenolate mofetil (MMF).	Recovered counts after addition of MMF.	No
Turgeman et al. [16]	73 Male	NSCLC	Nivolumab	5	G-4 ANC - 0	Crohn’s disease No serology	7 days	Not performed	Diarrhea	Methylprednisolone, GCSF	Neutrophils started improving after a week..	N/A
	74 Male	NSCLC	Nivolumab	11	G4 ANC-0	Negative Serology	2 days	Mildly hypercellular, unremarkable erythropoiesis and megakaryopoiesis, hyperplasia of myelocytic precursors	None	G-CSF, prednisolone	Recovered ANC after 2 days. Developed multiple relapses. Placed on Erlotinib, prophylactic GCSF.	No

Abbreviations: CTCAE Common terminology criteria for adverse events, ANC Absolute neutrophil count, G Grade, G-CSF Granulocyte colony stimulating factor, NSLC Non-small cell lung cancer, IVIG Intravenous immune globulin, ATG Anti-thymocyte globulin

Results are presented as cumulative of all cases. The median number of ICI cycles before patients presented with neutropenia was 3. All most all patients had nuetropenia ≥ G3. Median time to resolution of neutropenia wa approximaely 2 weeks. Rash seemed to be the most common associated irAE that preceeded or occurred concurrently with neutropenia. Prednisone. IVIG and filgrastim were the most common modalites used in management with variable sequence of administration. None of the patients restarted ICI after resolution of neutropenia