TY - JOUR
T1 - Discontinuation of combo immunotherapy and outcome of patients with melanoma brain metastases
AU - Mandalà, Mario
AU - Chen, Monica F
AU - Sullivan, Ryan J
AU - Sergi, Maria Chiara
AU - Postow, Michael
AU - Lawless, Aleigha R
AU - Effiom, Derek
AU - Peres, Tobias
AU - Lorigan, Paul C
AU - Serra-Bellver, Patricio
AU - Dummer, Reinhard
AU - Amaral, Teresa
AU - Rasch, Marie-Lena
AU - Giannarelli, Diana
AU - Vitale, Maria Grazia
AU - Helgadottir, Hildur
AU - Robert, Caroline
AU - Ubaldi, Martina
AU - Johnson, Douglas B
AU - Del Vecchio, Michele
AU - Indini, Alice
AU - Suijkerbuijk, Karijn P M
AU - Nathan, Paul
AU - Carter, Thomas
AU - Neyns, Bart
AU - Dirven, Iris
AU - Pires da Silva, Ines
AU - Menzies, Alexander Maxwell
AU - Zimmer, Lisa
AU - Livingstone, Elisabeth
AU - Depenni, Roberta
AU - Kähler, Katharina
AU - Hauschild, Axel
AU - Spagnolo, Francesco
AU - Di Giacomo, Anna Maria
AU - Arance, Ana
AU - Merelli, Barbara
AU - Quaglino, Pietro
AU - Rossi, Ernesto
AU - Tucci, Marco
AU - Guida, Michele
AU - Muñoz-Couselo, Eva
AU - Long, Georgina V
AU - Larkin, James
AU - Ascierto, Paolo A
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.
PY - 2026/5/4
Y1 - 2026/5/4
N2 - BACKGROUND: Nivolumab plus ipilimumab (COMBO) is the standard treatment for asymptomatic melanoma brain metastases (MBM), but current guidelines do not provide specific recommendations for treatment discontinuation in responding patients. This study aimed to evaluate outcomes after COMBO discontinuation within 24 months and the role of continuing treatment beyond 24 months.METHODS: Patients with MBM treated with COMBO who discontinued treatment within 24 months for reasons other than disease progression or continued beyond this time point were retrieved. Overall survival (OS), objective response, progression-free survival (PFS) and toxicities were analyzed.RESULTS: 465 patients were included: 392 discontinued COMBO within 24 months, while 73 continued beyond 24 months. Treatment was discontinued due to complete response (CR, n=47), partial response (PR, n=45), stable disease (SD, n=12), toxicity after SD (n=59), toxicity after CR (n=99), or toxicity after PR (n=130). At multivariable analysis, the line of treatment (>first vs first: HR 2.65 (1.62-4.32)), the immune-related adverse events (irrespective of anti-tumor necrosis factor-alpha) (HR 0.18 (0.07-0.42)); COMBO discontinuation after CR (HR 0.15 (0.05-0.40)), or PR (HR 0.08 (0.03-0.26)), as well as stopping due to toxicity after CR (HR 0.14 (0.07-0.27)) or PR (HR 0.51 (0.32-0.82)), were associated with OS. Notably, at a median follow-up of 51 months (IQR 31-70), patients with CR/PR who discontinued COMBO within 24 months had PFS and OS comparable to those who continued treatment beyond this time point. 4-year OS exceeded 83% in patients discontinuing COMBO after CR, PR, or toxicity following CR, compared with 66.4% in those discontinuing due to toxicity after PR; median PFS was not reached in the former groups but was 18.6 months in the toxicity after PR group.CONCLUSION: Discontinuation of COMBO within 24 months appears safe in patients with CR and in selected cases of PR, with no survival disadvantage versus prolonged therapy.
AB - BACKGROUND: Nivolumab plus ipilimumab (COMBO) is the standard treatment for asymptomatic melanoma brain metastases (MBM), but current guidelines do not provide specific recommendations for treatment discontinuation in responding patients. This study aimed to evaluate outcomes after COMBO discontinuation within 24 months and the role of continuing treatment beyond 24 months.METHODS: Patients with MBM treated with COMBO who discontinued treatment within 24 months for reasons other than disease progression or continued beyond this time point were retrieved. Overall survival (OS), objective response, progression-free survival (PFS) and toxicities were analyzed.RESULTS: 465 patients were included: 392 discontinued COMBO within 24 months, while 73 continued beyond 24 months. Treatment was discontinued due to complete response (CR, n=47), partial response (PR, n=45), stable disease (SD, n=12), toxicity after SD (n=59), toxicity after CR (n=99), or toxicity after PR (n=130). At multivariable analysis, the line of treatment (>first vs first: HR 2.65 (1.62-4.32)), the immune-related adverse events (irrespective of anti-tumor necrosis factor-alpha) (HR 0.18 (0.07-0.42)); COMBO discontinuation after CR (HR 0.15 (0.05-0.40)), or PR (HR 0.08 (0.03-0.26)), as well as stopping due to toxicity after CR (HR 0.14 (0.07-0.27)) or PR (HR 0.51 (0.32-0.82)), were associated with OS. Notably, at a median follow-up of 51 months (IQR 31-70), patients with CR/PR who discontinued COMBO within 24 months had PFS and OS comparable to those who continued treatment beyond this time point. 4-year OS exceeded 83% in patients discontinuing COMBO after CR, PR, or toxicity following CR, compared with 66.4% in those discontinuing due to toxicity after PR; median PFS was not reached in the former groups but was 18.6 months in the toxicity after PR group.CONCLUSION: Discontinuation of COMBO within 24 months appears safe in patients with CR and in selected cases of PR, with no survival disadvantage versus prolonged therapy.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Brain Neoplasms/drug therapy
KW - Female
KW - Humans
KW - Immunotherapy/methods
KW - Ipilimumab/therapeutic use
KW - Male
KW - Melanoma/drug therapy
KW - Middle Aged
KW - Nivolumab/therapeutic use
KW - Retrospective Studies
KW - Skin Neoplasms/drug therapy
KW - Treatment Outcome
U2 - 10.1136/jitc-2026-015063
DO - 10.1136/jitc-2026-015063
M3 - Article
C2 - 42082273
SN - 2051-1426
VL - 14
JO - Journal for immunotherapy of cancer
JF - Journal for immunotherapy of cancer
IS - 5
ER -