Abstract 1144P
Background
Metastatic uveal melanoma (mUM) is a rare disease, for which no systemic therapy has demonstrated overall survival (OS) benefit. Anti-PD1 +/- anti-CTLA4 ICI yields responses in 0-37% of mUM pts. This study evaluates the characteristics associated with ICI benefit in pts with mUM.
Methods
We performed a single-center retrospective cohort study of pts with mUM who received anti-PD1 +/- anti-CTLA4 ICI between 2014–19. Clinical characteristics, including baseline LDH and neutrophil to lymphocyte ratio (NLR) were abstracted from chart review. Treatment response (TR, any tumor shrinkage with no new growth) was determined by radiographic assessment and clinical progression was determined by physician assessment. Risk ratios (RR) and Fisher’s exact test were used to make comparisons between groups. Univariable and multivariable Cox regression models were used to assess clinical progression free survival (cPFS) and OS.
Results
Of 75 mUM pts who received ICI, 55 (73%) had anti-PD1 and 20 (27%) had anti-PD1 + anti-CTLA4. Pt characteristics were: 35 (47%) male, median age 64 yrs (34-89), 56 (75%) had 0-1 prior systemic therapies, 28 (37%) with NLR ≥4, 30 (40%) with LDH ≥1.5xULN, 34 (45%) were diagnosed (dx) stage IV <2 years after initial dx. The median OS from time of ICI was 10.0mo. TR to ICI was observed in 9 (12.2%) of pts. Characteristics associated with cPFS and OS are indicated in the table. Pts (n=25) with > 2yrs from initial dx to stage IV and LDH <1.5xULN were more likely to experience tumor shrinkage (RR 3.9; P=0.053), longer cPFS (5.8 vs. 2.4mo; HR 0.4; 95%CI 0.2-0.7; P=0.001) and longer OS (34.5 vs. 8.3mo; HR 0.3; 95%CI 0.1-0.5; P<0.001). Genomic analyses are ongoing. Table: 1144P
| Univariable | Multivariable | |||||
| HR | 95% CI | p-value | HR | 95% CI | p-value | |
| cPFS | ||||||
| Age >65 | 1.0 | 0.6-1.7 | 0.859 | - | - | - |
| Male | 0.8 | 0.5-1.3 | 0.389 | - | - | - |
| >1 prior therapy | 0.7 | 0.4-1.4 | 0.178 | - | - | - |
| PD1+CTLA4 vs. PD1 | 1.1 | 0.6-1.8 | 0.789 | - | - | - |
| LDH ≥1.5xULN | 2.4 | 1.4-3.9 | 0.001 | 3.8 | 2.2-6.8 | <0.001 |
| Initial dx to stg IV <2yrs | 1.8 | 1.1-2.9 | 0.016 | 2.2 | 1.3-3.7 | 0.002 |
| NLR ≥4 | 1.6 | 1.0-2.5 | 0.076 | 1.9 | 1.1-3.2 | 0.014 |
| OS | ||||||
| Age >65 | 1.8 | 1.1-3.2 | 0.030 | - | - | - |
| Male | 1.0 | 0.6-1.7 | 0.982 | - | - | - |
| >1 prior therapy | 0.7 | 0.4-1.3 | 0.283 | - | - | - |
| PD1+CTLA4 vs. PD1 | 1.2 | 0.6-2.3 | 0.588 | - | - | - |
| LDH ≥1.5xULN | 4.0 | 2.3-7.1 | <0.001 | 4.4 | 2.4-7.9 | <0.001 |
| initial dx to stg IV <2yrs | 1.9 | 1.1-3.3 | 0.016 | 2.5 | 1.4-4.3 | 0.002 |
| NLR ≥4 | 1.7 | 1.0-2.9 | 0.060 | 2.1 | 1.2-3.7 | 0.014 |
Conclusions
Clinical features associated with ICI treatment benefit in mUM include: LDH<1.5xULN, NLR<4 and time from initial dx to stage IV > 2years. In the absence of randomized controlled trials; real world evidence can be used to aid clinicians in optimizing treatment selection for mUM.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A.A.N. Rose: Spouse/Financial dependant: Merck. A. Spreafico: Advisory/Consultancy: Merck; Advisory/Consultancy: Bristol-Meyers Squibb; Advisory/Consultancy: Novartis; Advisory/Consultancy: Oncorus; Advisory/Consultancy: Janssen; Research grant/Funding (self): Merck; Research grant/Funding (self): Bayer; Research grant/Funding (self): Surface Oncology; Research grant/Funding (self): Novartis; Research grant/Funding (self): Bristol Meyers Squibb; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Northern Biologics; Research grant/Funding (self): Janssen; Research grant/Funding (self): Roche; Research grant/Funding (self): Regeneron; Research grant/Funding (self): Alkermes; Research grant/Funding (self): Array Biopharma. All other authors have declared no conflicts of interest.