TABLE 1.
Patient demographics, cancer staging, treatment details, and outcomes
| Characteristics | No = 71 (%) |
|---|---|
| Age; mean (+/-SD) (yr) | 62 ± 12 |
| Gender | |
| Male | 43 (61) |
| Female | 28 (39) |
| ECOG performance status | |
| 0 | 30 (42) |
| 1 | 41 (58) |
| AJCC | |
| III.D | 1 (1) |
| M1a | 16 (23) |
| M1b | 10 (14) |
| M1c | 32 (45) |
| M1d | 12 (17) |
| Anatomic site of primary | |
| Cutaneous | 58 (82) |
| Ocular | 4 (6) |
| Mucosal | 3 (4) |
| Unknown primary | 6 (8) |
| Line of systemic treatment for metastatic disease | |
| 1st line | 63 (89) |
| 2nd line | 8 (11) |
| Baseline LDH | |
| Elevated | 23 (32) |
| Normal | 49 (68) |
| Number of organs with metastatic involvement | |
| 1 | 25 (35) |
| 2 | 21 (30) |
| 3 | 11 (15) |
| > 3 | 14 20) |
| Actionable mutation | |
| BRAF wild type | 21 (30) |
| BRAF V600E | 28 (39) |
| BRAF V600K | 10 (14) |
| BRAF V600 - others | 1 (1) |
| NRAS | 11 (16) |
| Type of systemic treatment | |
| PD-1 inhibitors | 47 (66) |
| Combination of PD-1 and CTLA-4 inhibitors | 24 (34) |
| Tumor response on week 4 18F-FDG PET/CT | |
| Complete metabolic response | 3 (4) |
| Partial metabolic response | 12 (17) |
| Stable metabolic disease | 10 (14) |
| Heterogenous response | 6 (8) |
| Possible pseudoprogression | 20 (28) |
| Progressive metabolic disease | 17 (24) |
1 AJCC = American Joint Classification of Cancer; BRAF = V-Raf murine sarcoma viral oncogene homolog B; CTLA-4 = Cytotoxic T lymphocyte-associated antigen 4; ECOG = Eastern Cooperative Oncology Group; ICI = Immune checkpoint inhibitors; No = number of patients; NRAS = neuroblastoma RAS viral homolog; PD-1 = programmed death-1; SD = standard deviation
TABLE 2.
Clinical diagnosis of immune-related adverse events
| Immune-related adverse event | Any grade No (%) | Grade 3-5 No (%) | Time to onset of irAE (mean ± SD) [weeks] |
|---|---|---|---|
| No. of pts with at least one irAE | 56 (79) | 13 (18) | - |
| Number of all irAE events | 144 | 14 | 144 ± 161 |
| Gastrointestinal | |||
| Diarrhea | 14 (20) | 2 (3) | 31.7 ± 30.6 |
| Colitis | 7 (10) | 2 (3) | 39 ± 32 |
| Xerostomia | 2 (3) | 0 | 30.1 ± 4.4 |
| Gastritis | 2 (3) | 0 | 64.4 ± 7.7 |
| Stomatitis | 1 (1) | 0 | 3 ± 0 |
| Respiratory | |||
| Pneumonitis | 5 (7) | 0 (0) | 40.9 ± 45.7 |
| Sarcoid reaction | 2 (3) | 0 (0) | 6.3 ± 0.3 |
| Hepatic | |||
| Increased AST/ALT | 16 (23) | 4 (6) | 7.7 ± 8.3 |
| Endocrine | |||
| Hypothyroidism | 10 (14) | 0 | 12.3 ± 6 |
| Hyperthyroidism | 7 (10) | 0 | 7.3 ± 7.1 |
| Adrenal insufficiency | 2 (3) | 2 (3) | 34.4 ± 20.1 |
| Diabetes mellitus | 1 (1) | 1 (1) | 72.7 ± 0 |
| Pancreatitis | 1 (1) | 1 (1) | 32.4 ± 0 |
| Cutaneous | |||
| Pruritus | 23 (32) | 0 | 10.7 ± 10 |
| Skin rash | 16 (23) | 0 | 14 ± 16.3 |
| Vitiligo | 9 (13) | 0 | 37.4 ± 31.6 |
| Poliosis of hair | 1 (1) | 0 | 34.7 ± 0 |
| Musculoskeletal | |||
| Arthritis | 10 (14) | 0 | 28.7 ± 27.3 |
| Myalgia | 2 (3) | 0 | 16.7 ± 12.3 |
| Arthralgia | 1 (1) | 0 | 14 ± 0 |
| Synovitis | 1 (1) | 0 | 65.4 ± 0 |
| Neurological | |||
| Encephalitis | 2 (3) | 1 (1) | 36.4 ± 32.9 |
| Psychosis | 1 (1) | 0 | 25.4 ± 0 |
| Other | |||
| Fatigue | 6 (8) | 0 | 6.5 ± 4.9 |
| Hypophosphatemia | 1 (1) | 0 | 17 ± 0 |
FIGURE 1.
Kaplan-Meier curves show overall survival (OS) probability (A) and progression-free survival (PFS) probability (B) over time in patients with metastatic melanoma treated with immune checkpoint inhibitors. The grey shading reflects the 95% confidence interval.
FIGURE 2.
Swimmer plot shows individual patient’s treatment progression in each horizontal line. Colourful bars and lines indicate type and duration of treatment, while dots indicate specific action - 18F-FDG-PET/CT imaging or reason for end-of-study (if applicable). Vertical dashed lines indicate a time when 18F-FDG-PET/CT scan should be performed for patients in this study.
FIGURE 3.
Kaplan-Meier curves showing probability of median overall survival (OS) between clinical benefit (CB) and no-CB group as classified by findings on week four (W4) 18F-FDG PET/CT. The curves are statistically significantly different (p = 0.03).
FIGURE 4.
Alluvial plot illustrates the flow of patients between different response categories on 18F-FDG PET/CT scan across four evaluation time points: at week 4 (W4), week 16 (W16), week 48 (W48) and week 96 (W96).
CMR = complete metabolic response; HGR = heterogeneous response; PMD = progressive metabolic disease; PPD = pseudoprogressive disease; SMD = stable metabolic disease; PMR = partial metabolic response; n = number of patients
FIGURE 5.
Kaplan-Meier curves show the median overall survival (OS) probability of patients with metastatic melanoma treated with immune checkpoint inhibitors according to (A) LDH level and (B) the number of organs with metastatic involvement. The shading reflects the 95% confidence interval.
FIGURE 6.
Kaplan-Meyer curves of the median overall survival (OS) over time in patients with metastatic melanoma treated with immune checkpoint inhibitors according to (A) occurrence of immune-related adverse events, (B) occurrence of serious immune-related adverse events, (C) cutaneous immune-related side effects, (D) immune-related endocrine immune-related side effects. The blue and pink shading reflects the 95% confidence intervals for respecting groups.
FIGURE 7.
A 67-year-old male patient, diagnosed with metastatic NRAS-mutated cutaneous melanoma with lung metastases in January 2021, was treated with pembrolizumab in the first-line setting. Serial 18F-FDG PET/CT scans were obtained per the study protocol. The images above show the maximal intensity projection (MIP) on the baseline PET/CT (left), on the week 4 evaluation PET/CT (middle) and at the endpoint of the study (right). The images below show transverse sections of the lungs in different planes, revealing three FDG-avid metastatic nodules in the right lung (lower left images, red arrows), only small nodules with no FDG uptake on week 4 PET/CT (lower middle images, yellow arrows), a complete metabolic response, and no residual nodules found at the end point of the PET/CT images with persistent complete remission (lower right images).