Primary Resistance to PD-1-Based Immunotherapy—A Study in 319 Patients with Stage IV Melanoma
Abstract
:1. Introduction
2. Patients and Methods
2.1. Patients Cohort
2.2. Statistical Analysis
3. Results
3.1. Univariate and Multivariate Analysis
3.2. Survival Analysis
3.3. Second-Line Therapies and Outcomes
3.4. Pseudoprogression
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Characteristics | ICI Cohort n = 319 n (%) | n (%) | Univariate Analysis Test | Multivariate Logistic Regression Analysis | |
---|---|---|---|---|---|
Primary Resistance n = 127 (40) | DC (CR, PR, SD) n = 192 (60) | ||||
Age Distribution | 0.732 | ||||
Median (years [IQR]) | 68 (56–77) | 65 (55–78) | 68 (56–77) | ||
<60y | 101 (32) | 37 (29) | 64 (33) | ||
60y–75y | 114 (36) | 47 (37) | 67 (35) | ||
>75y | 104 (32) | 43 (34) | 61 (32) | ||
Sex | 0.049 | 0.822 | |||
Male | 192 (60) | 68 (54) | 124 (65) | ||
Female | 127 (40) | 59 (46) | 68 (35) | ||
Tumor localization * | 0.000 | 0.001 | |||
Head and neck | 54 (22) | 12 (13) | 42 (27) | ||
Trunk | 73 (29) | 18 (20) | 55 (34) | ||
Extremity | 109 (43) | 54 (59) | 55 (34) | ||
Other | 15 (6) | 7 (8) | 8 (5) | ||
Histological subtype * | 0.007 | 0.452 | |||
SSM | 76 (32) | 31(37) | 45 (29) | ||
NM | 72 (30) | 18(21) | 54 (35) | ||
LMM | 13 (6) | 0 | 13 (9) | ||
ALM | 30 (12) | 15 (18) | 15 (10) | ||
Mucosal | 15 (6) | 7 (8) | 8 (5) | ||
Other | 32 (14) | 14 (16) | 18 (12) | ||
Stage at initial diagnosis * | 0.114 | ||||
I | 48 (17) | 19 (18) | 29 (17) | ||
II | 84 (31) | 25 (23) | 59 (35) | ||
III | 95 (35) | 38 (37) | 57 (34) | ||
IV | 47 (17) | 24 (22) | 23 (14) | ||
Number of organs with metastases | 0.098 | 0.470 | |||
1-3 | 285 (89) | 109 (86) | 176 (92) | ||
>3 | 34 (11) | 18 (14) | 16 (8) | ||
Brain metastases | 0.618 | ||||
No | 258 (81) | 101 (79) | 157 (82) | ||
Yes | 61 (19) | 26 (21) | 35 (18) | ||
Liver metastases | 0.139 | ||||
No | 204 (64) | 75 (59) | 129 (67) | ||
Yes | 115 (36) | 52 (41) | 63 (33) | ||
BRAF mutation * | 0.844 | ||||
BRAFmut | 88 (45) | 32 (44) | 56 (46) | ||
BRAFwt | 106 (56) | 40 (56) | 66 (54) | ||
LDH level * | 0.029 | 0.532 | |||
Normal | 190 (68) | 67 (60) | 123 (73) | ||
Elevated | 90 (32) | 44 (40) | 46 (27) | ||
S100B level * | 0.000 | 0.008 | |||
Normal | 157 (56) | 44 (40) | 113 (65) | ||
Elevated | 125 (44) | 65 (60) | 60 (35) |
Best Response | Median OS (Months; 95% CI) | OS (%; 95% CI) | ||
---|---|---|---|---|
1-Year | 2-Year | 3-Year | ||
CR n = 50 (15.7%) | not reached | 100% | 95.7 (87.3–100) | 87.7 (70.8–100) |
PR n = 80 (25.1%) | not reached | 89.5 (82.1–96.9) | 84.4 (74.4–94.4) | 84.4 (74.4–94.4) |
SD n = 62 (19.4%) | 28 (22.9–33.1) | 86.3 (77.5–95.1) | 63.8 (47.7–79.9) | 24.6 (2.6–46.5) |
PD n = 127 (39.8%) | 11 (9.0–13.0) | 41.3 (31.9–50.7) | 14.7 (7.4–22.0) | 10.1 (3.4–16.8) |
DC n = 192 (60.2%) | not reached | 91.3 (87.0–95.6) | 81.0 (73.7–88.3) | 64.6 (53.2–76) |
PD-1 monotherapy n = 174 (66.2%) | 26 (19.7–32.3) | 71.1 (64.0–78.2) | 53.3 (45.1–61.5) | 41.3 (32.1–50.5) |
PD-1 + CTLA4 n = 145 (54.6%) | 31 (17.2–44.8) | 72.8 (65–80.6) | 54.5 (42.9–66.1) | 42.5 (24.1–60.9) |
Best Response | Median PFS (Months; 95% CI) | PFS (%; 95% CI) | ||
---|---|---|---|---|
1-Year | 2-Year | 3-Year | ||
CR n = 50 (15.7%) | Not reached | 87.6 (78.4–96.8) | 81.2 (68.9–93.5) | 72.2 (52.2–92.2) |
PR n = 80 (25.1%) | 37 (14.97–59.03) | 74.4 (64.2–85.0) | 62.7 (50.0–75.4) | 62.7 (50.0–75.4) |
SD n = 62 (19.4%) | 12 (8.97–15.03) | 43.0 (29.3–56.7) | 21.8 (6.3–37.3) | - |
PD n = 127 (39.8%) | 4 (3.56–4.44) | 8.7 (3.8–13.6) | 3.2 (0–6.5) | 1.1 (0–3.1) |
DC n = 192(60.2%) | 33 (20.4–45.6) | 68.1 (61.0–75.2) | 56.2 (51.8–64.8) | 48.7 (37.7–59.7) |
PD-1 monotherapy n = 174 (66.2%) | 8 (5.5–10.5) | 40.3 (32.7–47.9) | 30.5 (23.1–37.9) | 24.1 (16.3–31.9) |
PD-1 + CTLA4 n = 145 (54.6%) | 9 (1.8–16.2) | 48.5 (40.1–56.9) | 39 (29.2–78.8) | - |
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Amaral, T.; Seeber, O.; Mersi, E.; Sanchez, S.; Thomas, I.; Meiwes, A.; Forschner, A.; Leiter, U.; Eigentler, T.; Keim, U.; et al. Primary Resistance to PD-1-Based Immunotherapy—A Study in 319 Patients with Stage IV Melanoma. Cancers 2020, 12, 1027. https://doi.org/10.3390/cancers12041027
Amaral T, Seeber O, Mersi E, Sanchez S, Thomas I, Meiwes A, Forschner A, Leiter U, Eigentler T, Keim U, et al. Primary Resistance to PD-1-Based Immunotherapy—A Study in 319 Patients with Stage IV Melanoma. Cancers. 2020; 12(4):1027. https://doi.org/10.3390/cancers12041027
Chicago/Turabian StyleAmaral, Teresa, Olivia Seeber, Edgar Mersi, Stephanie Sanchez, Ioannis Thomas, Andreas Meiwes, Andrea Forschner, Ulrike Leiter, Thomas Eigentler, Ulrike Keim, and et al. 2020. "Primary Resistance to PD-1-Based Immunotherapy—A Study in 319 Patients with Stage IV Melanoma" Cancers 12, no. 4: 1027. https://doi.org/10.3390/cancers12041027