Key Points
- Cutaneous melanoma continues to be a serious public health threat with a slow but steady increase in annual incidence over the past four decades.
- In 2017, there were an estimated 87,110 new cases and 9,730 deaths due to melanoma in the United States.
- Since 2011, the treatment landscape for patients with melanoma has changed considerably with regulatory approval of 11 new drugs and/or combination regimens.
- Immunotherapy agents in particular have been associated with durable long-term survival in responding patients and have emerged as first-line treatment in most melanoma populations.
- The Society for Immunotherapy of Cancer (SITC), a non-profit professional organization dedicated to improving cancer patient outcomes through the use of immunotherapy, established an expert panel – the Melanoma Task Force – to provide consensus recommendations for clinical decision making for patients with melanoma.
- These recommendations are not intended to supplant sound clinical judgment but to provide clinicians who care for melanoma patients the most current thinking on how experts integrate immunotherapy into the treatment armamentarium for patients with advanced cutaneous melanoma.
Immunotherapy for Melanoma
Table 1. Clinical Issues in Tumor Immunotherapy for Cutaneous Melanoma
| Clinical Issue | Current Consensus Recommendations |
|---|---|
| Biomarker Status |
|
| Laboratory Assessment |
|
| Imaging Guidelines |
|
| Treatment Cessation |
|
Figure 1. Stage II Melanoma Immunotherapy Treatment Algorithm
Figure 2. Stage III N1a (7th)/Stage IIIA (8th) Melanoma Immunotherapy Treatment Algorithm
Figure 3. Stage III N1b-3 (AJCC 7th)/Stage IIIB-D (AJCC 8th)
Figure 4. Stage IV Melanoma Immunotherapy Treatment Algorithm
Table 2. Immunotherapy Agents for Melanoma
| Agent | Mechanism | FDA-approved indication |
|---|---|---|
| Cytokines | ||
| Interferon-α2b/pegylated interferon-α2b | High-risk adjuvant therapy | |
| High-dose interleukin-2 (IL-2) | Metastatic disease | |
| Immune Checkpoint Inhibitors | ||
| Ipilimumab | Blocks CTLA-4 | Metastatic and high-risk adjuvant melanoma |
| Nivolumab | Blocks PD-1 | Metastatic and high-risk adjuvant melanoma |
| Pembrolizumab | Blocks PD-1 | Metastatic melanoma |
| Ipilimumab/nivolumab | Blocks CTLA-4 and PD-1 | Metastatic melanoma |
| Oncolytic Virus | ||
| Talimogene laherparepvec (T-VEC) | Replicates within tumors and produces the immune stimulatory protein GM-CSF. Causes lysis of tumors followed by release of tumor-derived antigens, which together with virally derived GM-CSF may promote an antitumor immune response. | Intralesional therapy |
Definition of Evidence Grades
| Level | Definition |
|---|---|
| A | Strong supporting evidence-based data from prospective, randomized, controlled trials, meta-analyses, long-term follow-up of prospective, uncontrolled trials |
| B | Moderate supporting data from uncontrolled, prospective clinical trials |
| C | Weak supporting data from retrospective reviews and case reports |
| Percentages | Proportion of Task Force members favoring recommendation |
Abbreviations
ACTH, adrenocorticotropic hormone; BRAF+, positive for actionable BRAF mutations; BRAF–, negative for actionable BRAF mutations; CNS, central nervous system; CR, complete response; CT, computed tomography; CTLA-4, cytotoxic T lymphocyte antigen 4; FSH, follicle stimulating hormone; IL, interleukin; irAE, immune-related adverse event; LDH, lactate dehydrogenase; LH, luteinizing hormone; MRI, magnetic resonance imaging; NCCN, National Comprehensive Cancer Network; PD, progressive disease; PD-L1, programmed cell death 1 ligand; PET, positron emission tomography; PS, performance status; RFS, recurrence-free survival; TSH, thyroid stimulating hormone; T-VEC, talimogene laherparepvecSource
Sullivan RJ et al. An update on the Society for Immunotherapy of Cancer consensus statement on tumor immunotherapy for the treatment of cutaneous melanoma: version 2.0Disclaimer
This pocket guide attempts to define principles of practice that should produce high-quality patient care. It is applicable to specialists, primary care providers and ancillary healthcare providers. This pocket guide should not be considered exclusive of other methods of care reasonably directed at obtaining the same results. The ultimate judgment concerning the propriety of any course of conduct must be made by the clinician after consideration of each individual patient situation.Neither IGC, SITC, nor the authors endorse any product or service associated with the distributor of this clinical reference tool.