Table 1 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 |