Table 2 Characteristics of onset, duration, treatment and outcome of Immune Checkpoint Inhibitor induced neutropenia in 20 patients (ICI = Immune Checkpoint Inhibitor, G-CSF = Granulocyte-Colony Stimulating Factors, IVIG = Intravenous Immunoglobulins, irAE = Immune-related side effects, n.a. = not applicable)
ICI treatment | Onset | Treatment of neutropenia | Neutrophil recovery | Outcome | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Patient [ref] | ICI (mg/kg) | Number of cycles (cycle interval in weeks) | Documentation neutropenia (days after last ICI application) | Corticosteroids (dosage) | CSF (dosage) | IVIG (dosage) | ATG (dosage) | Other salvage therapy (dosage) | Neutrophil recovery achieved | Duration of neutropenia (days) | Recovery (days after salvage start) | Death during observation | Cause of death | irAE related death |
1 [9] | Ipilimumab (10) | 4 (3) | 14 | Prednisone p.o.; (1mg/kg/d) then dexamethasone i.v. (8mg/q6h) | G-CSF (480μg daily) | Yes (1g/kg/d) | No | Cyclosporin (2x100mg/d) | Yes | 8 | 8 | No | n.a. | n.a. |
2 [10] | Ipilimumab (3) | 3 (3) | 21 | Methylprednisolone i.v.(2x 1mg/kg/q12h ) | G-CSF (n.a.) | Yes (n.a.) | Yes (4 x 15mg/kg/d) | Cyclosporin (2x2.5mg/kg/d) | Yes | 20 | 4 | No | n.a. | n.a. |
3 [11] | Ipilimumab (3 then 10) | 4 (3) | 8 | Prednisone p.o. (1mg/kg/d) | G-CSF (10μg/kg/d) | Yes (1g/kg/d) | No | Romiplostin (1μg/kg/week) | Yes | 37 | n.a. | No | n.a. | n.a. |
4 [12] | Iplimumab (3) | 3 (3) | 12 | Methylprednisolone i.v. (2x 2mg/kg/d) | GM-CSF (n.a.) | No | No | No | Yes | 10 | 10 | Yes | Brain hemo-rrhage | No |
5 [12] | Ipilimumab (5) | 5 (2) | n.a. | Prednisone p.o. (1mg/kg/d) | GM-CSF (n.a.) | No | No | No | Yes | 7 | 7 | No | n.a. | n.a. |
6 [13] | Ipilimumab (3) | 3 (3) | 14 | Methylprednisolone i.v. (120mg/d) | G-CSF (480μg daily) | No | No | No | Yes | 16 | 8 | Yes | Progression | No |
7 [14] | Ipilimumab (10) | 4 (3) | 14 | Prednisone p.o. (60mg/d) | G-CSF (5μg/kg/d) | No | Yes (4 x 15mg/kg/d) | Cyclosporin (2 x 125mg/d) | Yes | 22 | 9 | No | n.a. | n.a. |
8 [15] | Nivolumab (3) | 2 (2) | 14 | Prednisone p.o. then i.v. (1.5-3mg/kg/d) | G-CSF (n.a.) | Yes (n.a.) | No | No | Yes | 16 | 14 | No | n.a. | n.a. |
9 [16] | Ipilimumab (3) and nivolumab (1 then 3) | 4 (3 then 2) | 3 | Prednisone p.o. (1mg/kg/d) | G-CSF (n.a.) | No | No | No | No | n.a. | n.a. | Yes | Brain hemo-rrhage | Yes |
10 [17] | Nivolumab (3) | 3 (2) | 7 | No | G-CSF (n.a.) | Yes (n.a.) | No | No | Yes | 7 | 3 | No | n.a. | n.a. |
11 [18] | Nivolumab (3) | 5 (2) | 12 | Methylprednisolone i.v. (1mg/kg/d) | G-CSF (n.a.) | No | No | No | Yes | 7 | 7 | Yes | Malignant cardiac arrythmia | No |
12 [18] | Nivolumab (3) | 11 (2) | 24 | Prednisone p.o. (1mg/kg/d) | G-CSF (n.a.) | Yes (n.a.) | No | No | Yes | 2 | 2 | Yes | Progression | No |
13 [19] | Nivolumab (3) | 2 (2) | 4 | Dexamethasone p.o. (2mg/2xd) | G-CSF (n.a.) | No | No | Eltrombopag (50-100mg for 3 days) | Yes | 64 | 22 | Yes | Unknown | n.a. |
14 [20] | Ipilimumab (3) and nivolumab (1) | 2 (2) | 7 | Methylprednisolone i.v. (75mg/d) | No | No | No | No | Yes | 17 | 8 | No | n.a. | n.a. |
15 [21] | Nivolumab (3) | 2 (2) | 4 | Methylprednisolone i.v. (500mg/d) | G-CSF (5μg/kg/d) | Yes (n.a.) | No | No | Yes | 48 | 25 | Yes | Progression | No |
16 [22] | Ipilimumab and nivolumab (not documented) | 2 (Not documented) | 5 | Methylprednisolone i.v. (2mg/kg/d ) | G-CSF (n.a.) | Yes (1g/kg/d) | No | No | Yes | 16 | 16 | No | n.a. | n.a. |
17 [23] | Pembrolizumab (not documented) | 4 (2) | 3 | Methylprednisolone i.v. (n.a.) | G-CSF (n.a.) | Yes (n.a.) | No | Cyclosporin (n.a.) | Yes | 12 | 12 | No | n.a. | n.a. |
18 [24] | Pembrolizumab (not documented) | 3 (3) | 22 | No | G-CSF (75μg daily) | No | No | No | Yes | 7 | 2 | No | n.a. | n.a. |
19 | Ipilimumab (3) and nivolumab (3) | 3 (3) | 12 | Methylprednisolone i.v. (80mg/d) | G-CSF (0.5/kg/d ) | No | No | No | Yes | 13 | 4 | Yes | Sepsis | Yes |
20 | Nivolumab and anti-LAG-3 | 3 (3) | 26 | Prednisone (1mg/kg/d), then methylprednisolone (1mg/kg/12h ) | G-CSF (0.5/kg/d ) | Yes (0.5g/kg/d) | No | No | Yes | 15 | 7 | No | n.a. | n.a. |
21 [25] | Nivolumab (3) | 1 | 16 | No | No | No | No | No | Yes | n.a. | n.a. | Yes | Progression | No |
22 [26] | Pembrolizumab (200mg absolut) | 4 (3) | 14 | Prednisone p.o. (80mg/d) | G-CSF (0.5/kg/d ) | No | No | No | Yes | 4 | 4 | Yes | Sepss | No |
23 [27] | Nivolumab (not documented) | 4 (not documented) | n.a. | No | No | Yes (n.a.) | No | No | No | >30 | n.a. | Yes | n.a. | Yes |
24 [27] | Nivolumab (not documented) | 1 (not documented) | n.a. | Prednisolon 1mg/kg/d | G-CSF (n.a.) | Yes (n.a.) | No | No | No | >73 | n.a. | Yes | Cardiac | No |
25 [27] | Nivolumab (not documented) | 6 (not documented) | n.a. | Prednisone 1mg/kg/d | G-CSF (n.a.) | No | No | No | No | >91 | n.a. | No | n.a. | n.a. |
26 [27] | Pembrolizumab (not documented) | 3 (not documented) | n.a. | Prednisone 1mg/kg/d | G-CSF (n.a.) | No | No | No | Yes | 12 | n.a. | No | n.a. | n.a. |
27 [27] | Nivolumab (not documented) | 5 (not documented) | n.a. | No | G-CSF (n.a.) | No | No | No | Yes | >195 | n.a. | No | n.a. | n.a. |
28 [27] | Nivolumab (not documented) | 1 (not documented) | n.a. | No | G-CSF (n.a.) | No | No | No | Yes | >111 | n.a. | No | n.a. | n.a. |
29 [27] | Pembrolizumab (not documented) | 1 (not documented) | n.a. | Prednisone 1mg/kg/d | G-CSF (n.a.) | No | No | No | No | 12 | n.a. | No | n.a. | n.a. |
30 [27] | Nivolumab (not documented) | 6 (not documented) | n.a. | No | G-CSF (n.a.) | No | No | No | Yes | 3 | n.a. | No | n.a. | n.a. |
31 [27] | Nivolumab (not documented) | 8 (not documented) | n.a. | No | G-CSF (n.a.) | No | No | No | No | >36 | n.a. | Yes | n.a. | Yes |
32 [27] | Nivolumab (not documented) | 5 (not documented) | n.a. | Prednisone 1mg/kg/d | G-CSF (n.a.) | No | No | No | Yes | 14 | n.a. | No | n.a. | n.a. |
33 [27] | Nivolumab (not documented) | 1 (not documented) | n.a. | No | G-CSF (n.a.) | No | No | No | No | 11 | n.a. | Yes | Progression | No |
34 [27] | Pembrolizumab (not documented) | 8 (not documented) | n.a. | Methylprednisolone i.v. (n.a.), then prednisone | G-CSF (n.a.) | No | No | No | No | 28 | n.a. | No | n.a. | n.a. |