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Table 1 Summary of recently pubmished cases with neutropenia due to immune checkpoint inhibitors

From: Isolated neutropenia as a rare but serious adverse event secondary to immune checkpoint inhibition

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
  1. 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
  2. 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