Abstract 1107P
Background
At present, the standard treatment for NRAS mutated MM is the same as for BRAF wild type MM with immune checkpoint inhibitors (ICIs) used as first line. It is thought that NRAS mutation is associated with better outcomes to immunotherapy. Nevertheless, retrospective studies reported controversial findings. To better understand the predictive role of NRAS mutation to ICIs, we assessed retrospectively clinical outcomes in two cohorts of pts homogeneously treated with ICIs as first line therapy: NRAS mutated/BRAF wild type MM (mut/wt) and NRAS wild/BRAF wild type MM (wt/wt).
Methods
A total of 331 pts including 163 mut/wt and 168 wt/wt were recruited in 11 Centres in Italy. The main evaluated pts features included: sex, age, origin and characteristics of primary cancer, previous adjuvant therapy, ECOG PS, M stage, metastatic sites, lactate dehydrogenase (LDH) level, basal count of white blood cells, lymphocyte and platelet, and subsequent therapies. In the wt/wt population, 35 pts received ipilimumab, 131 antiPD-1or antiPD-L1 and 2 the combination of both. In the cohort mut/wt, 45 patients received ipilimumab, 115 antiPD-1 and 3 the combination.
Results
As regard the primary, mut/wt was more frequently ulcerated (p.0038) and arose more frequently on the trunk (p.003) with respect wt/wt. At the onset of advanced stages, mut/wt had a higher M1c rate (p.001) involving less frequently lung (p.007) and brain (p.011) and progressing less to the brain if case be so (p.011). There was no significant difference in ORR, PFS and OS between the two groups (41.4%, 11 months [6-20, 95% CI] and 32 months [23-61, 95% CI] in mut/wt and 36,1%, 9 months [6-17, 95% CI] and 27 months [16-35, 95% CI] in wt/wt). Univariate analysis across the entire population showed a better ORR significatively associated with normal LDH, <3 sites of metastases, N/L ratio under 2.5 and the use of antiPD-1 than antiCTLA-4. A longer PFS and OS were also correlated with normal LDH, <3 sites of metastases, N/L ratio <2,5, lower platelet count and the use of antiPD-1 than antiCTLA-4.
Conclusions
We provide evidence that ICIs used as first line therapy are equally effective in mut/wt and wt/wt MM.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Guida: Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: for Bristol-Myers Squibb. P. Quaglino: Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Speaker Bureau/Expert testimony: Pierre Fabre; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Roche. A.M. Di Giacomo: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: GSK; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Sanofi. A.M. Minisini: Advisory/Consultancy: Novartis; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Pierre Fabre. P. Queirolo: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: GSK; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Sanofi. F. Spagnolo: Honoraria (self): BMS; Honoraria (self): Roche; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self): Sanofi; Honoraria (self): Merck; Honoraria (self), Advisory/Consultancy: Sunpharma; Honoraria (self), Advisory/Consultancy: Pierre-Fabre. All other authors have declared no conflicts of interest.