| Characteristic . | Patients, no. (%) . | ||
|---|---|---|---|
| Patients with irAE-n (n = 34) . | Controls (n = 44) . | P valuea . | |
| Female | 12 (35) | 16 (36) | .96 |
| Age, median (IQR), yrs | 66 (61–76) | 69 (60–76) | .91 |
| Neoplasm | |||
| Melanoma | 19 (56) | 23 (52) | .91 |
| Lung (NSCLC, SCLC) | 4 (12) | 6 (14) | .91 |
| Hepatocellular carcinoma | 2 (6) | 11 (25) | .07 |
| Other | 9 (27)b | 4 (9)c | .11 |
| Brain metastases | 5 (15) | 5 (11) | .85 |
| ICI therapy | |||
| PD-1 | 19 (56) | 26 (59) | .93 |
| PD-L1 | 5 (15) | 14 (32) | .18 |
| ICI combination (PD-1 + CTLA-4) | 10 (29) | 4 (9) | .06 |
| Additional treatment with bevacizumabd | 4 (12) | 8 (18) | .58 |
| IrAE-n | |||
| Myositis/myopathy | 15 (44) | — | — |
| Peripheral neuropathy (including GBS) | 14 (41) | — | — |
| Encephalitis | 8 (24) | — | — |
| CNS vasculitis | 1 (3) | ||
| Myasthenia gravis | 2 (6) | — | — |
| Patients with multiple irAE-n | 6 (18) | — | — |
| CTCAE of irAE-n, median (IQR) | 3 (3–4) | — | — |
| Concurrent nonneurological irAE (CTCAE > 2) | 17 (50) | — | — |
| No. of ICI cycles at V1, median (IQR) | 3 (2–6)e | 2 (2–2) | .28 |
| Time from ICI onset to V1, median (IQR), wks | 13 (8–25) | 6 (6–8) | <.01 |
| Treatment of irAE | |||
| Corticosteroids | 31 (91) | 2 (5) | <.001 |
| I.v. high-dose methylprednisolone (0.5–1 g/day) | 14 (41) | — | — |
| Intravenous immunoglobulins (IVIG) | 9 (26) | — | — |
| Plasma exchange | 2 (6) | — | — |
| Mycophenolate mofetil (MMF) | 1 (3) | — | — |
| Infliximab | 1 (3) | — | — |
| Outcome of irAE-n | |||
| Full recovery | 9 (26) | — | — |
| Relapsing-remitting/recovery with sequelae | 21 (62) | — | — |
| Fatal outcome | 4 (12) | — | — |
| Best overall tumor response (n = 34/43) | |||
| CR/PR | 16 (47) | 16 (37) | .59 |
| SD | 11 (32) | 18 (42) | .59 |
| PD | 7 (21) | 9 (21) | .97 |
| Progression free survival, median (IQR), mo (n = 29/ 43) | 11 (3–23) | 14 (6–20) | .59 |
| ICI stopped due to irAE-n (n = 23) | 19 (83) | — | — |
| ICI rechallenge (n = 13) | 2 (15) | — | — |
| Follow-up time after ICI initiation, median (IQR), mo (n = 33/43) | 24 (16–31) | 19 (14–22) | <.001 |
| Survival at 12 mo after ICI initiation (n = 33/43) | 26 (76) | 37 (84) | .59 |
| Characteristic . | Patients, no. (%) . | ||
|---|---|---|---|
| Patients with irAE-n (n = 34) . | Controls (n = 44) . | P valuea . | |
| Female | 12 (35) | 16 (36) | .96 |
| Age, median (IQR), yrs | 66 (61–76) | 69 (60–76) | .91 |
| Neoplasm | |||
| Melanoma | 19 (56) | 23 (52) | .91 |
| Lung (NSCLC, SCLC) | 4 (12) | 6 (14) | .91 |
| Hepatocellular carcinoma | 2 (6) | 11 (25) | .07 |
| Other | 9 (27)b | 4 (9)c | .11 |
| Brain metastases | 5 (15) | 5 (11) | .85 |
| ICI therapy | |||
| PD-1 | 19 (56) | 26 (59) | .93 |
| PD-L1 | 5 (15) | 14 (32) | .18 |
| ICI combination (PD-1 + CTLA-4) | 10 (29) | 4 (9) | .06 |
| Additional treatment with bevacizumabd | 4 (12) | 8 (18) | .58 |
| IrAE-n | |||
| Myositis/myopathy | 15 (44) | — | — |
| Peripheral neuropathy (including GBS) | 14 (41) | — | — |
| Encephalitis | 8 (24) | — | — |
| CNS vasculitis | 1 (3) | ||
| Myasthenia gravis | 2 (6) | — | — |
| Patients with multiple irAE-n | 6 (18) | — | — |
| CTCAE of irAE-n, median (IQR) | 3 (3–4) | — | — |
| Concurrent nonneurological irAE (CTCAE > 2) | 17 (50) | — | — |
| No. of ICI cycles at V1, median (IQR) | 3 (2–6)e | 2 (2–2) | .28 |
| Time from ICI onset to V1, median (IQR), wks | 13 (8–25) | 6 (6–8) | <.01 |
| Treatment of irAE | |||
| Corticosteroids | 31 (91) | 2 (5) | <.001 |
| I.v. high-dose methylprednisolone (0.5–1 g/day) | 14 (41) | — | — |
| Intravenous immunoglobulins (IVIG) | 9 (26) | — | — |
| Plasma exchange | 2 (6) | — | — |
| Mycophenolate mofetil (MMF) | 1 (3) | — | — |
| Infliximab | 1 (3) | — | — |
| Outcome of irAE-n | |||
| Full recovery | 9 (26) | — | — |
| Relapsing-remitting/recovery with sequelae | 21 (62) | — | — |
| Fatal outcome | 4 (12) | — | — |
| Best overall tumor response (n = 34/43) | |||
| CR/PR | 16 (47) | 16 (37) | .59 |
| SD | 11 (32) | 18 (42) | .59 |
| PD | 7 (21) | 9 (21) | .97 |
| Progression free survival, median (IQR), mo (n = 29/ 43) | 11 (3–23) | 14 (6–20) | .59 |
| ICI stopped due to irAE-n (n = 23) | 19 (83) | — | — |
| ICI rechallenge (n = 13) | 2 (15) | — | — |
| Follow-up time after ICI initiation, median (IQR), mo (n = 33/43) | 24 (16–31) | 19 (14–22) | <.001 |
| Survival at 12 mo after ICI initiation (n = 33/43) | 26 (76) | 37 (84) | .59 |
Values are median (interquartile range, IQR) or n (%). In cases of missing data, numbers of cases for patients with irAE-n and controls, respectively, are given in brackets next to each item. CTCAE, Common Terminology Criteria for Adverse Events; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; CR, complete remission; GBS, Guillain–Barré syndrome; ICI, immune checkpoint inhibitor; irAE-n, neurological immune-related adverse event; i.v., intravenous; mo, months; NSCLC, non–small cell lung cancer; PD, progressive disease; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; PR, partial remission; SD, stable disease; SCLC, small cell lung cancer; V1, visit 1 (timepoint of irAE-n diagnosis or follow-up after ICI therapy initiation for irAE-n patients and controls, respectively); wks, weeks; yrs, years.
aCorrected for multiple comparisons using the false discovery rate method.
bOne case of each: cholangiocarcinoma, prostate cancer, cervical cancer, urothelial cancer, Merkel-cell carcinoma, primary peritoneal carcinoma, oesophagogastric junctional adenocarcinoma, signet ring cell carcinoma, and kidney cancer.
cOne case of basal-cell carcinoma and squamous-cell carcinoma of the skin, 2 cases of Merkel-cell carcinoma.
dTen patients with hepatocellular carcinoma, one patient with cervical cancer, and one patient with primary peritoneal carcinoma received cotreatment with the VEGF-antagonist bevacizumab.
eFour patients had previous ICI therapy.
| Characteristic . | Patients, no. (%) . | ||
|---|---|---|---|
| Patients with irAE-n (n = 34) . | Controls (n = 44) . | P valuea . | |
| Female | 12 (35) | 16 (36) | .96 |
| Age, median (IQR), yrs | 66 (61–76) | 69 (60–76) | .91 |
| Neoplasm | |||
| Melanoma | 19 (56) | 23 (52) | .91 |
| Lung (NSCLC, SCLC) | 4 (12) | 6 (14) | .91 |
| Hepatocellular carcinoma | 2 (6) | 11 (25) | .07 |
| Other | 9 (27)b | 4 (9)c | .11 |
| Brain metastases | 5 (15) | 5 (11) | .85 |
| ICI therapy | |||
| PD-1 | 19 (56) | 26 (59) | .93 |
| PD-L1 | 5 (15) | 14 (32) | .18 |
| ICI combination (PD-1 + CTLA-4) | 10 (29) | 4 (9) | .06 |
| Additional treatment with bevacizumabd | 4 (12) | 8 (18) | .58 |
| IrAE-n | |||
| Myositis/myopathy | 15 (44) | — | — |
| Peripheral neuropathy (including GBS) | 14 (41) | — | — |
| Encephalitis | 8 (24) | — | — |
| CNS vasculitis | 1 (3) | ||
| Myasthenia gravis | 2 (6) | — | — |
| Patients with multiple irAE-n | 6 (18) | — | — |
| CTCAE of irAE-n, median (IQR) | 3 (3–4) | — | — |
| Concurrent nonneurological irAE (CTCAE > 2) | 17 (50) | — | — |
| No. of ICI cycles at V1, median (IQR) | 3 (2–6)e | 2 (2–2) | .28 |
| Time from ICI onset to V1, median (IQR), wks | 13 (8–25) | 6 (6–8) | <.01 |
| Treatment of irAE | |||
| Corticosteroids | 31 (91) | 2 (5) | <.001 |
| I.v. high-dose methylprednisolone (0.5–1 g/day) | 14 (41) | — | — |
| Intravenous immunoglobulins (IVIG) | 9 (26) | — | — |
| Plasma exchange | 2 (6) | — | — |
| Mycophenolate mofetil (MMF) | 1 (3) | — | — |
| Infliximab | 1 (3) | — | — |
| Outcome of irAE-n | |||
| Full recovery | 9 (26) | — | — |
| Relapsing-remitting/recovery with sequelae | 21 (62) | — | — |
| Fatal outcome | 4 (12) | — | — |
| Best overall tumor response (n = 34/43) | |||
| CR/PR | 16 (47) | 16 (37) | .59 |
| SD | 11 (32) | 18 (42) | .59 |
| PD | 7 (21) | 9 (21) | .97 |
| Progression free survival, median (IQR), mo (n = 29/ 43) | 11 (3–23) | 14 (6–20) | .59 |
| ICI stopped due to irAE-n (n = 23) | 19 (83) | — | — |
| ICI rechallenge (n = 13) | 2 (15) | — | — |
| Follow-up time after ICI initiation, median (IQR), mo (n = 33/43) | 24 (16–31) | 19 (14–22) | <.001 |
| Survival at 12 mo after ICI initiation (n = 33/43) | 26 (76) | 37 (84) | .59 |
| Characteristic . | Patients, no. (%) . | ||
|---|---|---|---|
| Patients with irAE-n (n = 34) . | Controls (n = 44) . | P valuea . | |
| Female | 12 (35) | 16 (36) | .96 |
| Age, median (IQR), yrs | 66 (61–76) | 69 (60–76) | .91 |
| Neoplasm | |||
| Melanoma | 19 (56) | 23 (52) | .91 |
| Lung (NSCLC, SCLC) | 4 (12) | 6 (14) | .91 |
| Hepatocellular carcinoma | 2 (6) | 11 (25) | .07 |
| Other | 9 (27)b | 4 (9)c | .11 |
| Brain metastases | 5 (15) | 5 (11) | .85 |
| ICI therapy | |||
| PD-1 | 19 (56) | 26 (59) | .93 |
| PD-L1 | 5 (15) | 14 (32) | .18 |
| ICI combination (PD-1 + CTLA-4) | 10 (29) | 4 (9) | .06 |
| Additional treatment with bevacizumabd | 4 (12) | 8 (18) | .58 |
| IrAE-n | |||
| Myositis/myopathy | 15 (44) | — | — |
| Peripheral neuropathy (including GBS) | 14 (41) | — | — |
| Encephalitis | 8 (24) | — | — |
| CNS vasculitis | 1 (3) | ||
| Myasthenia gravis | 2 (6) | — | — |
| Patients with multiple irAE-n | 6 (18) | — | — |
| CTCAE of irAE-n, median (IQR) | 3 (3–4) | — | — |
| Concurrent nonneurological irAE (CTCAE > 2) | 17 (50) | — | — |
| No. of ICI cycles at V1, median (IQR) | 3 (2–6)e | 2 (2–2) | .28 |
| Time from ICI onset to V1, median (IQR), wks | 13 (8–25) | 6 (6–8) | <.01 |
| Treatment of irAE | |||
| Corticosteroids | 31 (91) | 2 (5) | <.001 |
| I.v. high-dose methylprednisolone (0.5–1 g/day) | 14 (41) | — | — |
| Intravenous immunoglobulins (IVIG) | 9 (26) | — | — |
| Plasma exchange | 2 (6) | — | — |
| Mycophenolate mofetil (MMF) | 1 (3) | — | — |
| Infliximab | 1 (3) | — | — |
| Outcome of irAE-n | |||
| Full recovery | 9 (26) | — | — |
| Relapsing-remitting/recovery with sequelae | 21 (62) | — | — |
| Fatal outcome | 4 (12) | — | — |
| Best overall tumor response (n = 34/43) | |||
| CR/PR | 16 (47) | 16 (37) | .59 |
| SD | 11 (32) | 18 (42) | .59 |
| PD | 7 (21) | 9 (21) | .97 |
| Progression free survival, median (IQR), mo (n = 29/ 43) | 11 (3–23) | 14 (6–20) | .59 |
| ICI stopped due to irAE-n (n = 23) | 19 (83) | — | — |
| ICI rechallenge (n = 13) | 2 (15) | — | — |
| Follow-up time after ICI initiation, median (IQR), mo (n = 33/43) | 24 (16–31) | 19 (14–22) | <.001 |
| Survival at 12 mo after ICI initiation (n = 33/43) | 26 (76) | 37 (84) | .59 |
Values are median (interquartile range, IQR) or n (%). In cases of missing data, numbers of cases for patients with irAE-n and controls, respectively, are given in brackets next to each item. CTCAE, Common Terminology Criteria for Adverse Events; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; CR, complete remission; GBS, Guillain–Barré syndrome; ICI, immune checkpoint inhibitor; irAE-n, neurological immune-related adverse event; i.v., intravenous; mo, months; NSCLC, non–small cell lung cancer; PD, progressive disease; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; PR, partial remission; SD, stable disease; SCLC, small cell lung cancer; V1, visit 1 (timepoint of irAE-n diagnosis or follow-up after ICI therapy initiation for irAE-n patients and controls, respectively); wks, weeks; yrs, years.
aCorrected for multiple comparisons using the false discovery rate method.
bOne case of each: cholangiocarcinoma, prostate cancer, cervical cancer, urothelial cancer, Merkel-cell carcinoma, primary peritoneal carcinoma, oesophagogastric junctional adenocarcinoma, signet ring cell carcinoma, and kidney cancer.
cOne case of basal-cell carcinoma and squamous-cell carcinoma of the skin, 2 cases of Merkel-cell carcinoma.
dTen patients with hepatocellular carcinoma, one patient with cervical cancer, and one patient with primary peritoneal carcinoma received cotreatment with the VEGF-antagonist bevacizumab.
eFour patients had previous ICI therapy.
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