Abstract 5005
Background
In phase III trials, the results of ipilimumab plus nivolumab combination therapy (IPI+NIVO) are promising for metastatic melanoma (MM), despite many treatment-related grade 3-4 adverse events (AEs). Here, we report real-world outcomes of IPI+NIVO for MM.
Methods
Patients with (non-uveal) MM who received 1st-line IPI+NIVO between 2015 and 2017 were selected from the Dutch Melanoma Treatment Registry, a nation-wide population based registry. Probability of 2nd-line treatment was estimated with competing risk analysis and overall survival (OS) with Kaplan-Meier method and Cox regression analysis.
Results
In total, 2116 pts with MM were treated with systemic therapy of which 151 pts with 1st-line IPI+NIVO. Median age was 58yrs versus 64yrs for pts treated with other systemic therapy in 1st-line. Half of the pts treated with 1st-line IPI+NIVO had elevated LDH, 90% an ECOG PS of ≤ 1, 32% brain metastases (21% symptomatic), 87% stage IV-M1c and 42% had BRAF-mutated melanoma. Grade 3-4 AEs occurred in 90 pts (60%); 39 (26%) had colitis, 37 (25%) hepatitis and 22 (13%) endocrine insufficiency. No deaths due to AEs were reported. For 66 pts who stopped IPI+NIVO because of AEs, 1-yr survival probability was 76% (95%CI: 66-87) compared to 57% (95%CI: 47-69) for the remaining 85 (56%) patients treated with 1st-line IPI+NIVO. A total of 50 (33%) pts completed all 4 courses of IPI+NIVO and 44 (29%) pts received maintenance with NIVO. The 1- and 2-yr OS probabilities (95%CI) were 66% (58-74%) and 55% (46-65%). Probability of still being in 1st-line IPI+NIVO at 1- and 2-yrs was 50% (95%CI; 42-59) and 34% (95%CI; 25-45). Cumulative incidence for 2nd-line treatment and death at 1yr were respectively 24% (95%CI: 18-33) and 27% (95%CI: 20-34). Adjusted HR for ECOG PS of ≥ 2, symptomatic brain metastases, liver metastases were respectively 3.1 (95%CI; 1.2-8.3), 2.0 (95%CI; 1.0-3.8), 2.2 (95%CI; 1.2-4.2). HR for BRAF-wildtype status was 0.5 (95%CI; 0.2-0.9).
Conclusions
Half of pts receiving 1st-line IPI+NIVO for MM had elevated LDH, one third brain metastases and a majority ECOG PS ≤ 1. Nevertheless, OS is encouraging especially in pts who stopped treatment due to AEs. With appropriate patient selection in real-world, promising results can be achieved with 1st-line IPI+NIVO.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A.J.M. van den Eertwegh: Advisory / Consultancy: BMS; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Amgen. A.C.J. van Akkooi: Advisory / Consultancy: Amgen; Advisory / Consultancy: BMS; Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD - Merck; Advisory / Consultancy: MSD - Pfizer; Advisory / Consultancy: 4SC. J.W. de Groot: Advisory / Consultancy: BMS; Advisory / Consultancy: Merck. G.A.P. Hospers: Advisory / Consultancy: BMS; Advisory / Consultancy: Merck. E. Kapiteijn: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Merck. K.P.M. Suijkerbuijk: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Honoraria (institution), Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Honoraria (institution): Roche. A.A.M. Van der Veldt: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Ipsen. J.B.A.G. Haanen: Advisory / Consultancy: Amgen; Advisory / Consultancy: AZ; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Bayer; Advisory / Consultancy: Celsius Therapeutics; Advisory / Consultancy: GSK; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy, Research grant / Funding (institution): Neon Therapeutics; Advisory / Consultancy: AIMM; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Immunocore. All other authors have declared no conflicts of interest.
Resources from the same session
1802 - Evaluation of the anti-tumor efficacy and immune effects of N-809, a novel IL-15 superagonist/anti-PD-L1 bispecific agent
Presenter: Kristin Hicks
Session: Poster Display session 3
Resources:
Abstract
3190 - GI101, a novel triple-targeting bispecific CD80-IgG4-IL2variant fusion protein, elicits synergistic anti-tumor effects in preclinical models
Presenter: Jae Chan Park
Session: Poster Display session 3
Resources:
Abstract
4062 - Phase 1b, open-label, dose-escalation study of M9241 (NHS-IL12) plus avelumab in patients (pts) with advanced solid tumors
Presenter: Julius Strauss
Session: Poster Display session 3
Resources:
Abstract
5777 - THOR-707, a novel not-alpha IL-2, promotes all key immune system anti-tumoral actions of IL-2 without eliciting vascular leak syndrome (VLS)
Presenter: Marcos Milla
Session: Poster Display session 3
Resources:
Abstract
5047 - A phase I clinical trial of malignant pleural mesothelioma treated with locally delivered autologous anti-FAP-targeted CAR T-cells
Presenter: Alessandra Curioni
Session: Poster Display session 3
Resources:
Abstract
1679 - HPV16 E6-specific TCR-T armored with checkpoint blockade in the treatment of cervical cancer
Presenter: Paul Bryson
Session: Poster Display session 3
Resources:
Abstract
1133 - the Mutant Neoantigen Specific T Cell Is a Personalized Immunotherapy in Refractory Solid Tumor
Presenter: Qi Song
Session: Poster Display session 3
Resources:
Abstract
3338 - NY-ESO-1 and LAGE1A –an emerging target for cell therapies in solid tumours
Presenter: Ioanna Eleftheriadou
Session: Poster Display session 3
Resources:
Abstract
3089 - Targeting myeloid-derived suppressor cells and T cells: combination treatment with MTL-CEBPA and PD-1 antibody in a mouse syngeneic CT26 model
Presenter: Mikael Sodergren
Session: Poster Display session 3
Resources:
Abstract
5991 - Master Checkpoint Cbl-b Inhibition: Anti-tumor Efficacy in a Murine Colorectal Cancer Model Following siRNA-based Cell Therapy
Presenter: Kathrin Thell
Session: Poster Display session 3
Resources:
Abstract