Female melanoma patients show limited benefits from immunotherapy

December 2021 Clinical Practice Willem van Altena
Dermatologist examining birthmark on woman shoulder, closeup. Cancer prevention concept, empty space

Immune check point inhibitors (ICIs) have revolutionized the treatment landscape of many cancers including melanoma. Ipilimumab, pembrolizumab, and nivolumab are three ICIs approved for the treatment of advanced melanoma. When used in combination, these inhibitors have improved the prognosis of melanoma. Still, the overall ICI response rate remains low along with associated toxicities underscoring the need to identify factors for optimizing drug response.

New research published in JAMA Network Open December 2nd has investigated the association of biological markers such as sex with ICIs response in melanoma patients.

Study Design

The study examined the health records of patients from a national database of cancer patients – SEER (the Surveillance, Epidemiology, and End Results) linked with Medicare files. Data from 1,369 melanoma patients diagnosed between January 1, 1991, to December 31, 2015, who had undergone checkpoint inhibitors treatment (nivolumab plus ipilimumab combination therapy or anti–PD-1 therapy i.e., pembrolizumab or nivolumab) was included. The majority of patients were males (982) along with 387 females with a median age of 75 years (69-82 years). Overall survival (up to December 31, 2017) analysis was the primary outcome of the study.


The analysis of the data showed that the outcome of combination therapy (nivolumab plus ipilimumab) depended on sex (Wald χ2 = 9.48; P = .009 for interaction). Women had 2.06 times (95% CI, 1.28-3.32; P = .003) higher hazard ratio (HR), and 2.82 times higher mortality hazards than anti–PD-1 therapy (95% CI, 1.73-4.60), with prior ipilimumab use receiving combination therapy, as compared to male patients. Men or women receiving anti-PD-1 therapy with (HR, 0.97 [95% CI, 0.68-1.38]; P = .85) or without prior ipilimumab use (HR, 0.85 [95% CI, 0.67-1.07]; P = .16) showed no significant difference. Also, in men, no statistically significant difference was seen in the mortality risk between anti–PD-1 therapy and combination therapy.


Female patients with advanced melanoma show limited benefits from combination ICIs in comparison to male patients. Therefore, the sex of the patient must be considered before treatment decisions with ICIs in patients with advanced melanoma.


Furman WL, McCarville B, Shulkin BL, Davidoff A, et al. Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated With Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.18K322A. J Clin Oncol. 2021 Dec 6:JCO2101375. doi: 10.1200/JCO.21.01375. Epub ahead of print. PMID: 34871104.