Clinical Issues in Tumor Immunotherapy for Cutaneous Melanoma
| Clinical Issue | Current Consensus Recommendations |
|---|---|
| Biomarker Status | • The panel recognized the importance of identifying predictive biomarkers to aid in clinical decision-making• At present there are no validated biomarkers that reliably predict response to individual therapeutic agents• There is considerable interest in PD-L1 expression, mutation burden, lymphocyte infiltration, interferon-γ and related cytokine gene signatures as potential biomarkers• There are data suggesting higher response rates to monotherapy, but not combination therapy, with T cell checkpoint inhibitors when PD-L1 expression is increased but the panel does not recommend PD-L1 status be used outside of clinical trials |
| Laboratory Assessment | • Immunotherapy is associated with significant irAEs that require laboratory monitoring before and during active treatment• Clinicians should be alert for irAEs during therapy and for several months after stopping treatment• All panelists agreed that baseline and routine labs should include complete blood count, liver enzymes, metabolic panel, serum LDH and thyroid function studies (free T4, TSH)• Additional hormone levels should be assessed in patient with suspected treatment-related hypophysitis (free T4, TSH, ACTH, morning cortisol, cosyntropin stimulation test, LH, FSH, testosterone, prolactin) and early endocrinology referral• The frequency of laboratory testing was more controversial with most panelists recommending testing prior to each infusion for most drugs and less frequent surveillance during follow-up |
| Imaging Guidelines | • Confirming disease response/progression may be challenging with immunotherapy due to the delayed kinetics of response and induction of local inflammation• The panel (100%) recommends whole body imaging for melanoma patients treated with immunotherapy prior to starting and at regular intervals no more than 12 weeks apart while disease persists• A majority of the panel recommends imaging with CT scans of the chest, abdomen and pelvis and MRI of the brain• A minority recommend initial imaging with PET scans• Imaging should continue after complete responses at regular intervals for five years to identify recurrence |
| Treatment Cessation | • Since the kinetics of response to immunotherapy may be delayed decisions to stop treatment can be challenging• The panel recommended stopping treatment for any unresolved or recurrent high grade adverse event or when disease progression is confirmed by two independent imaging scans or clinical deterioration• Pseudo-progression has been reported for checkpoint inhibitors and T-VEC but is rare for interferon and IL-2; most panelists suggested that treatment with interferon or IL-2 should be stopped with any sign of disease progression• Repeat imaging within 1–2 months was recommended to confirm response or progression when pseudo-progression is suspected• Minority opinions included considering surgical resection for incomplete responses and tumor biopsy for equivocal cases |
Abbreviations: ACTH adrenocorticotropic hormone, CT computed tomography, FSH follicle stimulating hormone, LH luteinizing hormone, MRI magnetic resonance imaging, PD-L1 programmed cell death 1 ligand, PET positron emission tomography, TSH thyroid stimulating hormone