SUMMARY
Systemic treatment for irresectable or metastatic malignant melanoma has transformed over the past decade. For patients harbouring a BRAF V600 mutation, two standard treatment options exist, namely targeted therapy or anti-PD1 based therapy. For all other patients, immune checkpoint blockade based on monoclonal antibodies against anti-PD1 is considered the standard-of-care. Combination therapy with other checkpoint blockers such as anti-CTLA4 or anti-LAG3 are characterised by an improved outcome but are also associated with higher toxicity – which in case of the anti-PD1/anti-CTLA4 combination can be considerable. Up to date, patient selection for either monotherapy or combination therapy is largely based on patients’ demographics. Recent data suggest that treatment naïve patients with a BRAF V600 mutation have a better outcome when combination therapy with anti-CTLA4/anti-PD1 is given in first-line and BRAF/MEK inhibitory therapy is postponed to second-line. Patients who have exhausted their standard-of-care options should be included in a clinical trial and most scientific activity is evolving in the field of the immunotherapy refractory setting. A staggering number of different targets engaged in increasingly diverse subpopulations of immune effector- and regulator cells including the tumoral and stromal compartment are being explored in both the pre-clinical and clinical setting. These efforts will undoubtedly pave the way for the next transformation in the treatment of patients with malignant melanoma.
(BELG J MED ONCOL 2024;18(1):10–16)
