About Mucosal Melanoma (MM)
- About Mucosal Melanoma (MM)
MMs are a very rare type of cancer, accounting for approximately 1.2% of all melanomas. In the US, its rate is 2.2 MM cases per million per year compared to 153.5 for cutaneous melanomas. So, not only does melanoma originate in the skin (the most common presentation), it can also arise within the body on mucosal surfaces. Mucosal melanoma is not associated with any specific risk factors (genetic or otherwise), nor does it appear to be related to UV exposure.
Because of its rarity, MM is poorly understood, characterized, and studied. At MMW we are trying to change that, and aim to present some of the more recent information and data reflecting more hope than what one can currently find on the internet. The statistics presented on the internet reflect the years prior to the standard use of immunotherapy. Efforts are underway in the field to gain more comprehensive knowledge about how MM initiates and progresses, provide more specific biomarkers for MM early diagnosis, and offer more potentially effective treatment options for MM thereby, improving the life expectancy and quality for MM patients.
The standard use of immunotherapy and the experimental use of tumor infiltrating lymphocytes (TIL) have improved the response rate and overall survival of patients with MM, although it may take years for this new outcome data to be reflected in mainstream presented statistics. For example, a subset analysis from the CheckMate 067 Phase 3 study of nivolumab+ipilumab in advanced melanoma recently reported that in untreated, unresectable MM, 36% of patients were alive at 5 years after treatment with ipi/nivo (Shoushtari 2020 J Clin Onc; vol 38, issue 15 suppl). Adoptive cell therapy with TIL has shown promising results in advanced melanoma in multiple phase 1/2 trials, with response rates of 36-70%. A study in patients with advanced melanoma who had not been previously treated with immunotherapy showed that the combination of TIL plus pembrolizumab resulted in a 60% response rate, with a 30% complete response rate (O’Malley D, SITC 2021; Abstract 492). Additionally a recent Phase 3 study showed up to 20% complete response rate in patients who received prior treatment (Haanan, Annals of Oncology (2022) 33 (suppl_7): S808-S869). One of the largest Phase 2 studies reported an overall disease control rate of 80.3% and the median duration of response had not been reached, indicating the therapy induced very durable responses (Chesney JA Cancer Res. 2021;81(suppl 13);CT008), with some patients still in response 54 months post TIL (Sarnaik et al, SITC 2022). This data is very encouraging for patients with advanced melanoma, however none of these results break out the subgroup of MM patients separately.
- Primary Locations of MM
Mucosal Melanoma often goes misdiagnosed, mostly because of the anatomical locations of the disease and the lack of discernible signs and symptoms. Approximately 50% of MM arise in the head and neck region (oral/hard palate, sino-nasal), 25% in the anorectal region and 20% in the female genital tract (vaginal, vulvar). The remaining 5% include the esophagus, gallbladder, bowel, conjunctiva and urethra.
- Unexplained bleeding from the rectum
- Hemorrhoids that won’t heal or seem to worsen
- Pain during a bowel movement
- Oral/Hard Palate
- Pigmented spot or mass in mouth, cheeks or lips
- Sore in mouth that won’t heal
- Difficulty breathing
- Nose bleeds
- Blockage/pain in nasal passage
- Vaginal bleeding or discharge
- Pigmented spot or mass
- Treatment Options for MM
Treatment for MM depends on the size, type and location of the tumor, and whether it has metastasized (spread) at the time of diagnosis.
- Wide local excision is a standard surgical procedure for removal of tumors that are in a location where surgery is possible.
- Patients with melanoma that has spread to the lymph nodes may need lymphadenectomy, or surgery to remove the involved lymph nodes.
- For advanced melanoma, surgery is frequently combined with immunotherapy or targeted therapy. Therapy that is given before surgery is called neoadjuvant. Therapy that is given after surgery is called adjuvant.
- Radiation therapy is a local therapy which uses high doses of energy, such as photons or protons, to destroy cancer cells.
- Radiation can be used after surgery to kill remaining cancer cells or to shrink tumors in patients for whom surgery is a high risk or not possible.
- Radiation is not curative for mucosal melanoma but can lessen discomfort from large tumors.
- Chemotherapy/Immunotherapy/Targeted Therapy
- Chemotherapy is a systemic treatment option which uses drugs that stop the growth of cancer cells, either destroying them or stopping them from dividing. Chemotherapy can be given as a pill or as an injection into a blood vein. With the latest advances in targeted therapy and new immunotherapies, chemotherapy is used much less often to treat patients with mucosal melanoma.
- Immunotherapy is a treatment that stimulates the immune system to attack cancer cells. FDA-approved agents for MM include:
- Nivolumab + Relatlimab (Opdualag), an anti-PD-1 and anti-LAG-3 antibodies in combination
- Ipilimumab (Yervoy), an anti-CTLA-4 antibody
- Pembrolizumab (Keytruda), an anti-PD-1 antibody
- Nivolumab (Opdivo), an anti-PD-1 antibody
- Nivolumab (Opdivo) + Ipilimumab (Yervoy) in combination
- Targeted therapy is systemic treatment that focuses on specific molecules (or mutations) within cancer cells. The drugs work by blocking the function of these abnormal molecules to slow the growth and spread of melanoma and can be used with one another or in combination with other therapies. Research has identified a number of molecular pathways and mutated genes in melanoma, such as the BRAF, C-KIT, MEK and NRAS mutations. Patients who do not have these mutations do not benefit from medications targeting these pathways.
- Adoptive Cell Transfer/Tumor Infiltrating Lymphocytes (TIL)
Investigational TIL therapy is intended to make one’s own immune cells better able to attack cancer. A patient’s own T cells (called TIL) are collected from the patient’s tumor via surgery and then grown outside the body. The collected TIL are treated with substances that make them grow to large numbers quickly and then the TIL is delivered back to the patient. Once back inside the patient, the TIL should be able to recognize and target melanoma cells.
- Clinical Trials
Clinical trials can offer access to treatment approaches that could be beneficial for patients for which there is no effective standard of care, or if the standard of care has stopped working. However, there is no guarantee that a new treatment being tested in a research study will produce good results and there may be unknown risks. However, clinical trials generate the research that drives understanding of mucosal melanoma forward, potentially improving future treatment options for all patients.
Patients can discuss clinical trials with their doctor. A listing of clinical trials can be searched under mucosal melanoma at clinicaltrials.gov.