Investigating the Impact of Immune-Related Adverse Events, Glucocorticoid Use and Immunotherapy Interruption on Long-Term Survival Outcomes
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Data Collection
2.3. Statistical Analysis
3. Results
3.1. Patients, Disease and Treatment Characteristics
3.2. Immune-Related Adverse Events Characteristics and Glucocorticoid Use
3.3. Association between Immune-Related Adverse Events and Long-Term Outcomes
3.4. Association between Glucocorticoid Use and Long-Term Outcomes
3.5. Association between Immunotherapy Interruption and Long-Term Outcomes
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variable | All Treatment Types (n = 864) | CTLA-4 Inhibitor (n = 84) | PD(L)1 Inhibitor (n = 780) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
All Patients | Patients without Grade ≥ 3 Immune Related AE (n = 786) | Grade ≥ 3 Immune Related AE (n = 78) | p | All Patients | Patients without Grade ≥ 3 Immune Related AE (n = 64) | Grade ≥ 3 Immune Related AE (n = 20) | p | All Patients | Patients without Grade ≥ 3 Immune Related AE (n = 722) | Grade ≥ 3 Immune Related AE (n = 58) | p | |
Age, years, median (25th–75th) NA = 0 | 66 (58–73) | 66 (57–73) | 65 (56–72) | 0.41 | 63 (49–70) | 63 (50–73) | 61 (49–69) | 0.58 | 66 (58–73) | 66 (58–73) | 65 (59–75) | 0.97 |
Gender (%) NA = 0 | 0.12 | 0.41 | 0.047 | |||||||||
Male | 603 (70%) | 555 (71%) | 48 (62%) | 50 (60%) | 36 (56%) | 14 (70%) | 553 (71%) | 519 (72%) | 34 (59%) | |||
Female | 261 (30%) | 231 (29%) | 30 (38%) | 34 (40%) | 28 (44%) | 6 (30%) | 227 (29%) | 203 (28%) | 24 (41%) | |||
PS ≥ 2 (%) NA = 34 | 207 (25%) | 193 (26%) | 14 (19%) | 0.21 | 15 (18%) | 12 (19%) | 3 (15%) | 1.0 | 192 (26%) | 181 (26%) | 11 (20%) | 0.34 |
BMI (%) NA = 8 | 0.77 | 0.57 | ||||||||||
<18 | 63 (7%) | 56 (7%) | 7 (9%) | 3 (4%) | 3 (5%) | 0 (0%) | 60 (8%) | 53 (7%) | 7 (12%) | |||
18–30 | 684 (80%) | 623 (80%) | 61 (79%) | 68 (81%) | 50 (78%) | 18 (90%) | 616 (79%) | 573 (80%) | 43 (75%) | |||
>30 | 109 (13%) | 100 (13%) | 9 (12%) | 13 (16%) | 11 (17%) | 2 (10%) | 96 (12%) | 89 (12%) | 7 (12%) | 0.36 | ||
Primary tumor | <0.0065 | 1 | 0.74 | |||||||||
Lung cancer | 555 (64%) | 515 (65%) | 40 (51%) | 0 (0%) | 0 (0%) | 0 (0%) | 555 (71%) | 515 (71%) | 40 (69%) | |||
Melanoma | 230 (27%) | 197 (25%) | 33 (42%) | 84 (100%) | 64 (100%) | 20 (100%) | 146 (19%) | 133 (18%) | 13 (22%) | |||
Urologic cancer | 79 (9%) | 74 (9%) | 5 (6%) | 0 (0%) | 0 (0%) | 0 (0%) | 79 (10%) | 74 (10%) | 5 (9%) | |||
≥ 3 metastatic sites (%) NA = 0 | 306 (35%) | 276 (35%) | 30 (39%) | 0.62 | 44 (52%) | 32 (50%) | 12 (60%) | 0.46 | 262 (34%) | 244 (34%) | 18 (31%) | 0.77 |
Known brain metastases (%) NA = 0 | 229 (27%) | 212 (27%) | 17 (22%) | 0.39 | 23 (27%) | 18 (28%) | 5 (25%) | 1 | 206 (26%) | 194 (27%) | 12 (21%) | 0.38 |
Bone metastases (%) NA = 0 | 282 (33%) | 256 (33%) | 26 (33%) | 0.99 | 14 (17%) | 9 (14%) | 5 (25%) | 0.42 | 268 (34%) | 247 (34%) | 21 (36%) | 0.87 |
Visceral metastases (%) NA = 0 | 646 (75%) | 586 (75%) | 60 (77%) | 0.75 | 71 (85%) | 54 (84%) | 17 (85%) | 1 | 575 (74%) | 532 (74%) | 43 (74%) | 1.0 |
≥3rd line in metastatic setting (%) NA = 7 | 224 (26%) | 207 (27%) | 17 (22%) | 0.43 | 16 (19%) | 14 (22%) | 2 (10%) | 0.73 | 208 (27%) | 193 (27%) | 15 (26%) | 0.97 |
Smoking habits (%) NA = 41 | 0.73 | 0.15 | 0.51 | |||||||||
Active | 249 (30%) | 224 (30%) | 25 (33%) | 14 (17%) | 11 (18%) | 3 (15%) | 235 (32%) | 213 (31%) | 22 (39%) | |||
Stopped > 1 year | 366 (45%) | 335 (45%) | 31 (40%) | 16 (20%) | 9 (15%) | 7 (35%) | 350 (47%) | 326 (48%) | 24 (42%) | |||
Never | 208 (25%) | 187 (25%) | 21 (27%) | 52 (63%) | 42 (68%) | 10 (50%) | 156 (21%) | 145 (21%) | 11 (19%) | |||
Any history of autoimmune disorder (%) NA = 6 | 85 (10%) | 73 (9%) | 12 (15%) | 0.19 | 11 (13%) | 8 (13%) | 3 (15%) | 0.72 | 74 (10%) | 65 (9%) | 9 (15%) | 0.22 |
Any immune related AE (%) NA = 0 | 410 (47%) | _ | _ | _ | 54 (64%) | _ | _ | _ | 356 (46%) | _ | _ | _ |
Variable | CTLA-4 Inhibitors | PD(L)-1 Inhibitors | |||
---|---|---|---|---|---|
Melanoma (n = 84) | All Tumor Types (n = 780) | Lung Cancer (n = 555) | Melanoma (n = 146) | Urologic Cancer (n = 79) | |
Immune AE, grade ≥ 3 (%) | 20 (24%) | 58 (7%) | 40 (7%) | 13 (9%) | 5 (6%) |
Immune colitis, grade ≥ 3 (%) | 9 (11%) | 15 (2%) | 7 (1%) | 4 (3%) | 4 (5%) |
Immune rash, grade ≥ 3 (%) | 2 (2%) | 9 (1%) | 8 (1%) | 1 (1%) | 0 (0%) |
Hypophysitis, grade ≥ 3 (%) | 4 (5%) | 6 (1%) | 2 (0%) | 3 (2%) | 1 (1%) |
Immune hepatitis, grade ≥ 3 (%) NA = 0 | 6 (7%) | 6 (1%) | 4 (1%) | 2 (1%) | 0 (0%) |
Immune pneumopathy, grade ≥ 3 (%) | 1 (5%) | 5 (1%) | 8 (1%) | 1 (1%) | 1 (1%) |
Immune cardiac AE, grade ≥ 3 (%) | 0 (0%) | 4 (1%) | 4 (1%) | 0 (0%) | 0 (0%) |
Immune nephritis, grade ≥ 3 (%) | 0 (0%) | 1 (0%) | 0 (0%) | 1 (1%) | 0 (0%) |
Other immune AE, grade ≥ 3 (%) | 3 (4%) | 17 (2%) | 13 (2%) | 3 (2%) | 1 (1%) |
Management | CTLA-4 Inhibitors | PD(L)-1 Inhibitors | Gr ≥ 3 Colitis | Gr ≥ 3 Hypophysitis | Gr ≥ 3 Dermatitis | Gr ≥ 3 Hepatitis |
---|---|---|---|---|---|---|
Melanoma (n = 20) | All Tumors Type (n = 58) | n = 24 | n = 10 | n = 11 | n = 12 | |
Glucocorticoids use, number of patients | 13 (65%) | 32 (55%) | 14 (74%) | 4 (40%) | 6 (55%) | 7 (58%) |
Glucocorticoid dose | ||||||
≤0.5 μγ/κγ | 0 (0%) | 7 (22%) | 0 (0%) | 0 (0%) | 1 (17%) | 0 (0%) |
1 mg/kg | 5 (38%) | 20 (62%) | 10 (71%) | 2 (50%) | 3 (50%) | 3 (43%) |
≥2 μγ/κγ | 8 (61%) | 5 (16%) | 4 (29%) | 2 (50%) | 2 (33%) | 4 (57%) |
Glucocorticoids attack treatment duration in days, median (25th–75th) | 42 (30–58) | 47 (29–84) | 40 (30–77) | 20 (8–33) | 39 (35–52) | 42 (30–44) |
Glucocorticoids maintenance, number of patients | 5 (25%) | 18 (31%) | 6 (25%) | 1 (10%) | 3 (27%) | 4 (33%) |
Other immunosuppressive treatment | 2 (10%) | 6 (10%) | 2 (8%) | 1 (10%) | 2 (18%) | 1 (8%) |
ICI interruption | 14 (70%) | 50 (86%) | 16 (84%) | 5 (50%) | 8 (73%) | 10 (83%) |
ICI reintroduction | 4 (29%) | 16 (32%) | 3 (19%) | 3 (60%) | 3 (38%) | 3 (30%) |
Time to reintroduction, in days, median (25th–75th) | 36 (31–42) | 39 (24–72) | 28 (28–48) | 45 (37–85) | 31 (26–96) | 41 (36–45) |
New irAE after reintroduction | 2 (50%) | 7 (32%) | 0 (0%) | 3 (100%) | 0 (0%) | 1 (33%) |
<2016, n = 25 | 2016–2017 , n = 32 | >2017, n = 21 | p | |
---|---|---|---|---|
ICI interruption | 18 (72%) | 30 (94%) | 16 (76%) | 0.069 |
CTC use | 16 (64%) | 17 (53%) | 12 (57%) | 0.71 |
(a) p value Fisher test = 0.0056 | ||
No CTC | CTC | |
No interruption | 11 (79%) | 3 (21%) |
Interruption | 22 (34%) | 42 (66%) |
(b) p value Fisher test = 1.0 | ||
Other irAE | Colitis, myositis, pneumonitis, hepatitis | |
No interruption | 10 (71%) | 4 (29%) |
Interruption | 43 (67%) | 21 (33%) |
(c) p value Fisher test = 0.029 | ||
Other gr3-4 irAE | Gr 3-4 Colitis, myositis, pneumonitis, hepatitis | |
No CTC | 27 (82%) | 6 (18%) |
CTC | 26 (58%) | 19 (42%) |
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Bruyère, C.L.d.l.; Souquet, P.-J.; Dalle, S.; Corbaux, P.; Boespflug, A.; Duruisseaux, M.; Kiakouama-Maleka, L.; Reverdy, T.; Maugeais, M.; Sahin, G.; et al. Investigating the Impact of Immune-Related Adverse Events, Glucocorticoid Use and Immunotherapy Interruption on Long-Term Survival Outcomes. Cancers 2021, 13, 2365. https://doi.org/10.3390/cancers13102365
Bruyère CLdl, Souquet P-J, Dalle S, Corbaux P, Boespflug A, Duruisseaux M, Kiakouama-Maleka L, Reverdy T, Maugeais M, Sahin G, et al. Investigating the Impact of Immune-Related Adverse Events, Glucocorticoid Use and Immunotherapy Interruption on Long-Term Survival Outcomes. Cancers. 2021; 13(10):2365. https://doi.org/10.3390/cancers13102365
Chicago/Turabian StyleBruyère, Charline Lafayolle de la, Pierre-Jean Souquet, Stéphane Dalle, Pauline Corbaux, Amélie Boespflug, Michaël Duruisseaux, Lize Kiakouama-Maleka, Thibaut Reverdy, Madeleine Maugeais, Gulsum Sahin, and et al. 2021. "Investigating the Impact of Immune-Related Adverse Events, Glucocorticoid Use and Immunotherapy Interruption on Long-Term Survival Outcomes" Cancers 13, no. 10: 2365. https://doi.org/10.3390/cancers13102365