Immune checkpoint (IC) inhibitor drug holidays are safe in patients with metastatic melanoma who achieve an objective response (OR) during therapy, according to a study of more than 200 patients in Poland.
More than 80% of patients maintained disease control without progression at 24 months after discontinuing immunotherapy. Those who had received IC inhibitor therapy for at least 24 months and achieved a complete response (CR) during therapy had the best outcomes, Anna M. Czarnecka, MD, reported at the 11th World Congress of Melanoma (WCM) and 21st EADO Congress 2025.
Notably, re-initiation of immunotherapy in those who progressed during the drug holiday also allowed for objective disease control, said Czarnecka of the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
She and her colleagues enrolled 222 consecutive patients with unresectable or metastatic melanoma who were treated at least 6 months with an immunotherapy based on anti–programmed death-1 and who achieved at least stable disease (SD).
The patients underwent imaging every 16 weeks during the drug holiday and were followed for a median of 63 months. Median time on IC inhibitor therapy before a drug holiday was 26 months.
Median overall survival (OS) was not reached, but 5-year OS was 86.2%, Czarnecka noted.
“At 1 year, more than 87% of patients were progression free, and at 3 years it was more than 60%,” she said.
Overall, 95 patients achieved a CR, and of those, 19 progressed during the drug holiday and seven restarted treatment. Sixty-five achieved a partial response (PR), and of those, 20 progressed and 10 restarted treatment. Sixty-five achieved SD, 29 of those progressed, and 22 restarted treatment.
Younger age was associated with longer drug holiday duration, but gender and disease subtype and stage were not significantly associated with drug holiday duration.
Of 39 patients who progressed during the drug holiday and restarted IC inhibitor therapy, 58.9% achieved an OR and 46.4% achieved progression-free survival (PFS) after 1 year. Median PFS in this subset of patients was 11.2 months.
Responses on IC inhibitor retreatment were CR in 16 patients, PR in seven patients, and SD in 16 patients. Of those who achieved a post–drug holiday OR, three included CRs in patients who had also achieved a CR during their initial IC inhibitor therapy.
Again, only younger age was significantly associated with OR during retreatment and with PFS, those treated for at least 24 months achieved the best outcomes, Czarnecka noted.
Median OS after the drug holiday started was not reached, but the 5-year rate was 79.3%.
Median PFS since the start of the holiday was not reached, but 3-year PFS was 65% for all patients and 72.4% among those who achieved CR.
The optimal duration of IC inhibitor therapy in routine clinical practice has not been clearly defined for patients with metastatic melanoma, and debates regarding de-escalation strategies are ongoing. These findings suggest an intentional immunotherapy suspension until disease progression is a safe and effective approach in patients who achieve a response during initial treatment, she concluded.
Czarnecka disclosed relationship with BMS, MSD, Novartis, and Perre Fabre.
Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X: @SW_MedReporter.
