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» Home » CAD » Oncology » Malignancy of the Skin » Melanoma
Background
Melanoma is a malignant melanocyte tumor. Melanocytes are the cells that produce the pigment melanin and are generated from the neural crest. While most melanomas begin on the skin, they can also develop on mucosal surfaces or in other locations where neural crest cells migrate, such as the uveal tract.
Uveal melanomas exhibit considerable differences in incidence, prognostic variables, molecular features, and treatment from cutaneous melanoma. Patients with stage 0 melanoma have a five-year relative survival rate of 97 percent, compared to roughly 10% for those with stage IV cancer.
Epidemiology
The global incidence of malignant melanoma is increasing at a higher rate than that of any other cancer, except for lung cancer in women. Melanoma is more common in white people than in black people and Asian people. It is the fifth most prevalent cancer in males and the seventh most common cancer in women, accounting for 5% and 4% of all new cancer cases, respectively.
The average age upon diagnosis is 57 years, and up to 75% of patients are under the age of 70. Melanoma is known for primarily affecting young and middle-aged individuals, as opposed to other solid tumors, which primarily affect older adults. It is most common in people under the age of 55, and it is responsible for the third-highest number of deaths among all cancers.
Anatomy
Pathophysiology
Melanomas can grow in or near a precancerous lesion or in otherwise seemingly healthy skin. Melanomas which develop in healthy skin arise de novo, without any signs of precursor lesions.
Solar exposure is the most common cause for melanomas. Melanoma can also develop in parts of the skin that are not exposed to the sun, such as the palms, soles, and perineum.
Certain lesions are regarded as precursors to melanoma. Among these are nevi such as:
Melanomas grow in two distinct stages: radial and vertical. In the epidermis, malignant cells develop radially during the radial growth phase. Most melanomas advance to the vertical development phase over time, during which malignant cells infiltrate the dermis and acquire the ability to spread.
Classifications of melanomas are done according to their depth. Lesions under 1mm are classified as thin; between 1-4mm are moderate; larger than 4mm are thick.
Melanomas are classified according to their growth patterns. The 4 main types of melanomas are:
These account for approximately 70% of melanomas. They are usually flat but can become irregular and elevated in later stages. The lesions are about 2 cm in diameter and have a variety of colors, as well as external notches, indentations, or both.
They are responsible for 15-30% of melanoma diagnoses. Tumors caused are generally pigmented blue-black, but sometimes might be colorless.
These account for approximately 4-10% of melanomas, mostly resulting in tumors larger than 3cm. Beginning as small, freckle-like lesions; they develop into larger flat lesions with peripheral notching.
These are responsible for 2-8% melanomas in whit-skinned individuals, and 35-60% melanomas in black-skinned individuals. They commonly appear as flat, brown or tan stains on the palms with shapeless borders. Lesions near the toes or fingers are darker; brown or black, and often lead are accompanied with ulcerations in later stages of the disease.
Etiology
5-10% patients have family history; the risk of affliction increases by 2.2 times if at least one relative has the disease. Physical characteristics such as blue eyes, red hair, pale complexion, or individuals easily burned by the sun have higher incidence rates of the disease.
Individuals with immunocompromised states such as patients with transplants, or hematological malignancies are more commonly affected. Patients with high exposure to UVB and UVA rays; especially those who wear sunscreen are more affected.
Recent evidence indicates that sunscreen blocks UVB radiations, so individuals are more exposed to UVA rays. Use of tanning beds, numbers of sunburns, and low latitude also increases incidence of melanomas.
A recent survey also found that individuals with a lower socioeconomic status have worse outcomes due to lower melanoma risk perception and lack of knowledge about the disease.
Genetics
If any of your direct relatives (parents, brothers, sisters, or children) has had melanoma, your risk of developing it is increased. Around 10% of all melanoma patients have a family history of the disease.
A common family lifestyle of regular sun exposure, a family tendency to have pale skin, gene mutations that run in families, or a combination of these factors presents a higher risk of developing this condition.
Most specialists don’t recommend genetic testing to check for mutations that may increase risk in individuals with a family history of melanoma, because genetic testing is still not a reliable diagnostic tool for this condition.
Instead, experts recommend individuals with family history of melanoma to examine their skin regularly. Such individuals are also suggested to avoid facilities such as tanning beds (man-made UV exposure) and be cautious of sun exposure.
Prognostic Factors
Factors that indicate a poor prognosis are:
Thickness of the tumor (worse outcomes with thicker lesions)
Tumor in regional lymph nodes indicates stage III of disease-
The stage of the disease during diagnosis greatly affects the prognosis. Patients diagnosed during the first stage have a 5-year survival rate of more than 90%; stage 2 patients have a 5-year survival rate between 45%-77%, and the 5-year survival rate for patients in the 3rd stage is between 27%-70%.
If the disease is discovered after metastasis has developed, the prognosis is generally very bleak. The average survival rate for such patients is below 20%.
Clinical History
Physical Examination
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
by Stage
by Modality
Chemotherapy
Radiation Therapy
Surgical Interventions
Hormone Therapy
Immunotherapy
Hyperthermia
Photodynamic Therapy
Stem Cell Transplant
Targeted Therapy
Palliative Care
Medication
60
mg
Tablet
Oral
once a day
21
days
Take the dose until disease progression or unacceptable toxicity
Metastatic melanoma:
2
mg
oral
once a day
as a single agent or in combination with dabrafenib
45
mg
Tablet
Orally
every 12 hrs
The dose is given in combination with encorafenib; continue the therapy until disease progression or severe health side effects
Dose Adjustments
Renal Dose Adjustments: No adjustment is recommended. Liver Dose Adjustments: For hepatic impairment, a dose of 30 mg orally twice a day is recommended
3 mg per kg given IV over 90 minutes every three weeks for a maximum of 4 doses
Adjuvant treatment of melanoma:
10 mg per kg given IV over 90mins every three weeks for four doses, followed by 10 mg per kg given IV over 90mins every 12 weeks for up to 3yrs
Monotherapy:
200
mg
Intravenous (IV)
every 3 weeks or 400 mg IV every 6 weeks and administer it over 30 minutes; continue the treatment until disease progression or unacceptable toxicity
Adjuvant treatment: 200 mg IV every 3 weeks OR 400 mg IV every 6 weeks and administer it over 30 minutes; continue the treatment until disease progression or unacceptable toxicity or up to 12 months
2 - 4.5
mg/kg
Intravenous (IV)
once a day
10
days
; repeat every 4 weeks
OR
250 mg/m2 Intravenous (IV) once a day 5 days; repeat every 3 weeks
6
mcg/kg
Subcutaneous (SC)
once a week
for 8 doses, followed by 3 mcg/kg once a week up to 5 years
Induction phase:
20 million IU/m2/day IV through 20-minute infusion 5 days per week for 4 weeks Maintenance phase: 10 million IU/m2 SC 3 times a week for 48 weeks
20 mcg intravenously on day 1
30 mcg intravenously on day 8
68 mcg intravenously from the next week until toxicity is reduced
Adjuvant Treatment of Melanoma:
Recommended for melanoma in patients who have undergone complete resection and have lymph node involvement or metastatic disease in the adjuvant context
240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks
Continue the therapy until the unacceptable toxicity or disease progression for up to a year
Unresectable or Metastatic Melanoma
It is indicated for single-agent use or in combination with ipilimumab.
Single-agent
240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks
Continue until the disease is progressed or unacceptable toxicity is achieved
In combination with ipilimumab
1 mg/kg nivolumab intravenously every 3 weeks, with
3 mg/kg ipilimumab intravenously on the same day (maximum of 4 doses)
After completion of combination therapy: administer 240 mg nivolumab intravenously every 2 weeks or 480 mg intravenously every 4 weeks
Continue the therapy until the disease is progressed or unacceptable toxicity is reduced
encorafenib treats metastatic melanoma. It is given in combination with binimetinib as 450 mg orally, four times daily.
Dose Modifications:
If binimetinib is held back, reduce encorafenib maximum to a dose of 300 mg/day
1st dose reduction: 300 mg orally each day
2nd dose reduction: 225 mg orally each day
Subsequently, discontinue the dose permanently if unable to tolerate more than 225 mg/day
(Orphan)
Treatment of stage II B is through stage IV melanoma
starting dose: about 4 mL concentration of 106 (one million) PFU/mL
Second dose: about 4 mL concentration in 108 (100 million) PFU/mL administered three weeks after the initial therapy
All subsequent therapies (reinitiation included): about 4 mL concentration in 108 (100 million) PFU/mL administered two weeks after the previous therapy
Continue therapy for 6 months or till there are no more injectable lesions.
If unresectable subcutaneous, cutaneous, or nodal lesions develop after a full response, restart therapy.
Determine the dose volume for every lesion
The size of a lesion depends on its longest dimension.
When the lesions are grouped together, they should be injected as a singular lesion based on the following:
Above 5 cm: 4 mL/lesion
Above 2.5 to 5 cm: 2 mL/lesion
Above 1.5 to 2.5 cm: 1 mL/lesion
Above 0.5 to 1.5 cm: 0.5 mL/lesion
Below 0.5 cm: 0.1 mL/lesion
Dose Adjustments
Dosage Modifications
Renal or Hepatic impairment: there are No clinical trials have been conducted on the pharmacokinetics of talimogene laherparepvec with renal or hepatic impairment.
480 mg of nivolumab/160 mg of relatlimab Intravenous every four Weeks
Continue till unacceptable toxicity or disease progression occurs
Dose Adjustments
Dosage Modifications
Immune mediated adverse reactions (IMARs) general dose modifications
IMARs of severe (Grade 3): Delay
Life-threatening Recurrent severe (Grade 3) or Grade 4 Inability to lower corticosteroid dosage to 10 mg or less on prednisone or an equivalent within 12 weeks of starting steroids or IMARs requiring systemic immunosuppressive therapy: discontinue permanently
Pneumonitis
Grade 2
Delay therapy; Resume once complete or partial improvement (Grade below 1) has been achieved following corticosteroid tapering
If there isn't any complete or partial improvement within 12 weeks of starting steroids or if prednisone cannot be reduced to below 10 mg/day (or an equivalent amount) within 12 weeks of starting steroids, permanently discontinue.
Grade 3 and 4: Discontinue permanently
Colitis
Grade 2 and 3
Delay therapy; Resume once complete or partial improvement (Grade below 1) has been achieved following corticosteroid tapering
If there isn't any complete or partial improvement within 12 weeks of starting steroids or if prednisone cannot be reduced to below 10 mg/day (or an equivalent amount) within 12 weeks of starting steroids, permanently discontinue.
Grade 4: Discontinue permanently
Hepatitis
Total bilirubin increasing to more than 1.5 and 3 times ULN or AST or ALT increasing to more than 3 and 8 times ULN: Delay therapy; Resume once complete or partial improvement (Grade below 1) has been achieved following corticosteroid tapering
If there isn't any complete or partial improvement within 12 weeks of starting steroids or if prednisone cannot be reduced to below 10 mg/day (or an equivalent amount) within 12 weeks of starting steroids, permanently discontinue.
AST or ALT increasing to more than 8 times ULN or TB increasing to more than 3 times ULN: discontinue Permanently
Endocrinopathies
Grade 3 and 4: Delay till clinically gets stable or discontinue permanently based on the severity
Nephritis with the renal impairment
Grade 2 and 3 increased blood creatinine
Delay therapy; Resume once complete or partial improvement (Grade below 1) has been achieved following corticosteroid tapering
If there isn't any complete or partial improvement within 12 weeks of starting steroids or if prednisone cannot be reduced to below 10 mg/day (or an equivalent amount) within 12 weeks of starting steroids, permanently discontinue.
Grade 4 increase in the blood creatinine levels: discontinue Permanently
Dermatologic Exfoliative conditions
toxic epidermal necrolysis (TEN), Suspected Stevens-Johnson Syndrome (SJS), or Drug Rash with Eosinophilia Systemic Symptoms (DRESS): Delay therapy
Confirmed SJS, DRESS or TEN: discontinue Permanently
Myocarditis
Grade 2, 3, and 4: discontinue Permanently
Neurologic toxicities
Grade 2
Delay therapy; Resume once complete or partial improvement (Grade below 1) has been achieved following corticosteroid tapering
If there isn't any complete or partial improvement within 12 weeks of starting steroids or if prednisone cannot be reduced to below 10 mg/day (or an equivalent amount) within 12 weeks of starting steroids, permanently discontinue.
Grade 3 and 4: discontinue Permanently
Infusion-related reactions
Grade 1 or 2: slow the infusion rate or interrupt
Grade 3 or 4: discontinue Permanently
Hepatic impairment
Mild and moderate (TB below 3 times ULN and at any AST): dosage adjustment is not necessary
Severe: pharmacokinetics effects of relatlimab and nivolumab are not known
Renal impairment
Mild and moderate (eGFR 30 to 89 mL/min/1.73 m2): dosage adjustment is not necessary
Severe: pharmacokinetics effects of relatlimab and nivolumab are not known
Safety and efficacy not established
Safety and efficacy not established
Age: >12yrs
3 mg per kg given IV over 90 minutes every three weeks for a maximum of 4 doses
Adjuvant treatment of melanoma:
10 mg per kg given IV over 90mins every three weeks for four doses, followed by 10 mg per kg given IV over 90mins every 12 weeks for up to 3yrs
Indicated for Unresectable or Metastatic Melanoma as a single-agent use or in combination with ipilimumab.
Single-agent
• For <12 years: 3 mg/kg intravenously every 2 weeks or 6 mg/kg intravenously every 4 weeks
• For >12 years: 240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks
• Continue until the disease is progressed or unacceptable toxicity is achieved
In combination with ipilimumab
• 1 mg/kg nivolumab intravenously every 3 weeks, with 3 mg/kg ipilimumab intravenously on the same day (maximum of 4 doses)
• After completion of combination therapy administer nivolumab
• For >12 years: 240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks
• Continue the therapy until the disease is progressed or unacceptable toxicity is reduced
Future Trends
References
https://www.cancer.org/cancer/melanoma-skin-cancer/causes-risks-prevention/risk-factors.htmlhttps://www.ncbi.nlm.nih.gov/books/NBK470409/
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» Home » CAD » Oncology » Malignancy of the Skin » Melanoma
Melanoma is a malignant melanocyte tumor. Melanocytes are the cells that produce the pigment melanin and are generated from the neural crest. While most melanomas begin on the skin, they can also develop on mucosal surfaces or in other locations where neural crest cells migrate, such as the uveal tract.
Uveal melanomas exhibit considerable differences in incidence, prognostic variables, molecular features, and treatment from cutaneous melanoma. Patients with stage 0 melanoma have a five-year relative survival rate of 97 percent, compared to roughly 10% for those with stage IV cancer.
The global incidence of malignant melanoma is increasing at a higher rate than that of any other cancer, except for lung cancer in women. Melanoma is more common in white people than in black people and Asian people. It is the fifth most prevalent cancer in males and the seventh most common cancer in women, accounting for 5% and 4% of all new cancer cases, respectively.
The average age upon diagnosis is 57 years, and up to 75% of patients are under the age of 70. Melanoma is known for primarily affecting young and middle-aged individuals, as opposed to other solid tumors, which primarily affect older adults. It is most common in people under the age of 55, and it is responsible for the third-highest number of deaths among all cancers.
Melanomas can grow in or near a precancerous lesion or in otherwise seemingly healthy skin. Melanomas which develop in healthy skin arise de novo, without any signs of precursor lesions.
Solar exposure is the most common cause for melanomas. Melanoma can also develop in parts of the skin that are not exposed to the sun, such as the palms, soles, and perineum.
Certain lesions are regarded as precursors to melanoma. Among these are nevi such as:
Melanomas grow in two distinct stages: radial and vertical. In the epidermis, malignant cells develop radially during the radial growth phase. Most melanomas advance to the vertical development phase over time, during which malignant cells infiltrate the dermis and acquire the ability to spread.
Classifications of melanomas are done according to their depth. Lesions under 1mm are classified as thin; between 1-4mm are moderate; larger than 4mm are thick.
Melanomas are classified according to their growth patterns. The 4 main types of melanomas are:
These account for approximately 70% of melanomas. They are usually flat but can become irregular and elevated in later stages. The lesions are about 2 cm in diameter and have a variety of colors, as well as external notches, indentations, or both.
They are responsible for 15-30% of melanoma diagnoses. Tumors caused are generally pigmented blue-black, but sometimes might be colorless.
These account for approximately 4-10% of melanomas, mostly resulting in tumors larger than 3cm. Beginning as small, freckle-like lesions; they develop into larger flat lesions with peripheral notching.
These are responsible for 2-8% melanomas in whit-skinned individuals, and 35-60% melanomas in black-skinned individuals. They commonly appear as flat, brown or tan stains on the palms with shapeless borders. Lesions near the toes or fingers are darker; brown or black, and often lead are accompanied with ulcerations in later stages of the disease.
5-10% patients have family history; the risk of affliction increases by 2.2 times if at least one relative has the disease. Physical characteristics such as blue eyes, red hair, pale complexion, or individuals easily burned by the sun have higher incidence rates of the disease.
Individuals with immunocompromised states such as patients with transplants, or hematological malignancies are more commonly affected. Patients with high exposure to UVB and UVA rays; especially those who wear sunscreen are more affected.
Recent evidence indicates that sunscreen blocks UVB radiations, so individuals are more exposed to UVA rays. Use of tanning beds, numbers of sunburns, and low latitude also increases incidence of melanomas.
A recent survey also found that individuals with a lower socioeconomic status have worse outcomes due to lower melanoma risk perception and lack of knowledge about the disease.
If any of your direct relatives (parents, brothers, sisters, or children) has had melanoma, your risk of developing it is increased. Around 10% of all melanoma patients have a family history of the disease.
A common family lifestyle of regular sun exposure, a family tendency to have pale skin, gene mutations that run in families, or a combination of these factors presents a higher risk of developing this condition.
Most specialists don’t recommend genetic testing to check for mutations that may increase risk in individuals with a family history of melanoma, because genetic testing is still not a reliable diagnostic tool for this condition.
Instead, experts recommend individuals with family history of melanoma to examine their skin regularly. Such individuals are also suggested to avoid facilities such as tanning beds (man-made UV exposure) and be cautious of sun exposure.
Factors that indicate a poor prognosis are:
Thickness of the tumor (worse outcomes with thicker lesions)
Tumor in regional lymph nodes indicates stage III of disease-
The stage of the disease during diagnosis greatly affects the prognosis. Patients diagnosed during the first stage have a 5-year survival rate of more than 90%; stage 2 patients have a 5-year survival rate between 45%-77%, and the 5-year survival rate for patients in the 3rd stage is between 27%-70%.
If the disease is discovered after metastasis has developed, the prognosis is generally very bleak. The average survival rate for such patients is below 20%.
60
mg
Tablet
Oral
once a day
21
days
Take the dose until disease progression or unacceptable toxicity
Metastatic melanoma:
2
mg
oral
once a day
as a single agent or in combination with dabrafenib
45
mg
Tablet
Orally
every 12 hrs
The dose is given in combination with encorafenib; continue the therapy until disease progression or severe health side effects
Dose Adjustments
Renal Dose Adjustments: No adjustment is recommended. Liver Dose Adjustments: For hepatic impairment, a dose of 30 mg orally twice a day is recommended
3 mg per kg given IV over 90 minutes every three weeks for a maximum of 4 doses
Adjuvant treatment of melanoma:
10 mg per kg given IV over 90mins every three weeks for four doses, followed by 10 mg per kg given IV over 90mins every 12 weeks for up to 3yrs
Monotherapy:
200
mg
Intravenous (IV)
every 3 weeks or 400 mg IV every 6 weeks and administer it over 30 minutes; continue the treatment until disease progression or unacceptable toxicity
Adjuvant treatment: 200 mg IV every 3 weeks OR 400 mg IV every 6 weeks and administer it over 30 minutes; continue the treatment until disease progression or unacceptable toxicity or up to 12 months
2 - 4.5
mg/kg
Intravenous (IV)
once a day
10
days
; repeat every 4 weeks
OR
250 mg/m2 Intravenous (IV) once a day 5 days; repeat every 3 weeks
6
mcg/kg
Subcutaneous (SC)
once a week
for 8 doses, followed by 3 mcg/kg once a week up to 5 years
Induction phase:
20 million IU/m2/day IV through 20-minute infusion 5 days per week for 4 weeks Maintenance phase: 10 million IU/m2 SC 3 times a week for 48 weeks
20 mcg intravenously on day 1
30 mcg intravenously on day 8
68 mcg intravenously from the next week until toxicity is reduced
Adjuvant Treatment of Melanoma:
Recommended for melanoma in patients who have undergone complete resection and have lymph node involvement or metastatic disease in the adjuvant context
240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks
Continue the therapy until the unacceptable toxicity or disease progression for up to a year
Unresectable or Metastatic Melanoma
It is indicated for single-agent use or in combination with ipilimumab.
Single-agent
240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks
Continue until the disease is progressed or unacceptable toxicity is achieved
In combination with ipilimumab
1 mg/kg nivolumab intravenously every 3 weeks, with
3 mg/kg ipilimumab intravenously on the same day (maximum of 4 doses)
After completion of combination therapy: administer 240 mg nivolumab intravenously every 2 weeks or 480 mg intravenously every 4 weeks
Continue the therapy until the disease is progressed or unacceptable toxicity is reduced
encorafenib treats metastatic melanoma. It is given in combination with binimetinib as 450 mg orally, four times daily.
Dose Modifications:
If binimetinib is held back, reduce encorafenib maximum to a dose of 300 mg/day
1st dose reduction: 300 mg orally each day
2nd dose reduction: 225 mg orally each day
Subsequently, discontinue the dose permanently if unable to tolerate more than 225 mg/day
(Orphan)
Treatment of stage II B is through stage IV melanoma
starting dose: about 4 mL concentration of 106 (one million) PFU/mL
Second dose: about 4 mL concentration in 108 (100 million) PFU/mL administered three weeks after the initial therapy
All subsequent therapies (reinitiation included): about 4 mL concentration in 108 (100 million) PFU/mL administered two weeks after the previous therapy
Continue therapy for 6 months or till there are no more injectable lesions.
If unresectable subcutaneous, cutaneous, or nodal lesions develop after a full response, restart therapy.
Determine the dose volume for every lesion
The size of a lesion depends on its longest dimension.
When the lesions are grouped together, they should be injected as a singular lesion based on the following:
Above 5 cm: 4 mL/lesion
Above 2.5 to 5 cm: 2 mL/lesion
Above 1.5 to 2.5 cm: 1 mL/lesion
Above 0.5 to 1.5 cm: 0.5 mL/lesion
Below 0.5 cm: 0.1 mL/lesion
Dose Adjustments
Dosage Modifications
Renal or Hepatic impairment: there are No clinical trials have been conducted on the pharmacokinetics of talimogene laherparepvec with renal or hepatic impairment.
480 mg of nivolumab/160 mg of relatlimab Intravenous every four Weeks
Continue till unacceptable toxicity or disease progression occurs
Dose Adjustments
Dosage Modifications
Immune mediated adverse reactions (IMARs) general dose modifications
IMARs of severe (Grade 3): Delay
Life-threatening Recurrent severe (Grade 3) or Grade 4 Inability to lower corticosteroid dosage to 10 mg or less on prednisone or an equivalent within 12 weeks of starting steroids or IMARs requiring systemic immunosuppressive therapy: discontinue permanently
Pneumonitis
Grade 2
Delay therapy; Resume once complete or partial improvement (Grade below 1) has been achieved following corticosteroid tapering
If there isn't any complete or partial improvement within 12 weeks of starting steroids or if prednisone cannot be reduced to below 10 mg/day (or an equivalent amount) within 12 weeks of starting steroids, permanently discontinue.
Grade 3 and 4: Discontinue permanently
Colitis
Grade 2 and 3
Delay therapy; Resume once complete or partial improvement (Grade below 1) has been achieved following corticosteroid tapering
If there isn't any complete or partial improvement within 12 weeks of starting steroids or if prednisone cannot be reduced to below 10 mg/day (or an equivalent amount) within 12 weeks of starting steroids, permanently discontinue.
Grade 4: Discontinue permanently
Hepatitis
Total bilirubin increasing to more than 1.5 and 3 times ULN or AST or ALT increasing to more than 3 and 8 times ULN: Delay therapy; Resume once complete or partial improvement (Grade below 1) has been achieved following corticosteroid tapering
If there isn't any complete or partial improvement within 12 weeks of starting steroids or if prednisone cannot be reduced to below 10 mg/day (or an equivalent amount) within 12 weeks of starting steroids, permanently discontinue.
AST or ALT increasing to more than 8 times ULN or TB increasing to more than 3 times ULN: discontinue Permanently
Endocrinopathies
Grade 3 and 4: Delay till clinically gets stable or discontinue permanently based on the severity
Nephritis with the renal impairment
Grade 2 and 3 increased blood creatinine
Delay therapy; Resume once complete or partial improvement (Grade below 1) has been achieved following corticosteroid tapering
If there isn't any complete or partial improvement within 12 weeks of starting steroids or if prednisone cannot be reduced to below 10 mg/day (or an equivalent amount) within 12 weeks of starting steroids, permanently discontinue.
Grade 4 increase in the blood creatinine levels: discontinue Permanently
Dermatologic Exfoliative conditions
toxic epidermal necrolysis (TEN), Suspected Stevens-Johnson Syndrome (SJS), or Drug Rash with Eosinophilia Systemic Symptoms (DRESS): Delay therapy
Confirmed SJS, DRESS or TEN: discontinue Permanently
Myocarditis
Grade 2, 3, and 4: discontinue Permanently
Neurologic toxicities
Grade 2
Delay therapy; Resume once complete or partial improvement (Grade below 1) has been achieved following corticosteroid tapering
If there isn't any complete or partial improvement within 12 weeks of starting steroids or if prednisone cannot be reduced to below 10 mg/day (or an equivalent amount) within 12 weeks of starting steroids, permanently discontinue.
Grade 3 and 4: discontinue Permanently
Infusion-related reactions
Grade 1 or 2: slow the infusion rate or interrupt
Grade 3 or 4: discontinue Permanently
Hepatic impairment
Mild and moderate (TB below 3 times ULN and at any AST): dosage adjustment is not necessary
Severe: pharmacokinetics effects of relatlimab and nivolumab are not known
Renal impairment
Mild and moderate (eGFR 30 to 89 mL/min/1.73 m2): dosage adjustment is not necessary
Severe: pharmacokinetics effects of relatlimab and nivolumab are not known
Safety and efficacy not established
Safety and efficacy not established
Age: >12yrs
3 mg per kg given IV over 90 minutes every three weeks for a maximum of 4 doses
Adjuvant treatment of melanoma:
10 mg per kg given IV over 90mins every three weeks for four doses, followed by 10 mg per kg given IV over 90mins every 12 weeks for up to 3yrs
Indicated for Unresectable or Metastatic Melanoma as a single-agent use or in combination with ipilimumab.
Single-agent
• For <12 years: 3 mg/kg intravenously every 2 weeks or 6 mg/kg intravenously every 4 weeks
• For >12 years: 240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks
• Continue until the disease is progressed or unacceptable toxicity is achieved
In combination with ipilimumab
• 1 mg/kg nivolumab intravenously every 3 weeks, with 3 mg/kg ipilimumab intravenously on the same day (maximum of 4 doses)
• After completion of combination therapy administer nivolumab
• For >12 years: 240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks
• Continue the therapy until the disease is progressed or unacceptable toxicity is reduced
https://www.cancer.org/cancer/melanoma-skin-cancer/causes-risks-prevention/risk-factors.htmlhttps://www.ncbi.nlm.nih.gov/books/NBK470409/
Melanoma is a malignant melanocyte tumor. Melanocytes are the cells that produce the pigment melanin and are generated from the neural crest. While most melanomas begin on the skin, they can also develop on mucosal surfaces or in other locations where neural crest cells migrate, such as the uveal tract.
Uveal melanomas exhibit considerable differences in incidence, prognostic variables, molecular features, and treatment from cutaneous melanoma. Patients with stage 0 melanoma have a five-year relative survival rate of 97 percent, compared to roughly 10% for those with stage IV cancer.
The global incidence of malignant melanoma is increasing at a higher rate than that of any other cancer, except for lung cancer in women. Melanoma is more common in white people than in black people and Asian people. It is the fifth most prevalent cancer in males and the seventh most common cancer in women, accounting for 5% and 4% of all new cancer cases, respectively.
The average age upon diagnosis is 57 years, and up to 75% of patients are under the age of 70. Melanoma is known for primarily affecting young and middle-aged individuals, as opposed to other solid tumors, which primarily affect older adults. It is most common in people under the age of 55, and it is responsible for the third-highest number of deaths among all cancers.
Melanomas can grow in or near a precancerous lesion or in otherwise seemingly healthy skin. Melanomas which develop in healthy skin arise de novo, without any signs of precursor lesions.
Solar exposure is the most common cause for melanomas. Melanoma can also develop in parts of the skin that are not exposed to the sun, such as the palms, soles, and perineum.
Certain lesions are regarded as precursors to melanoma. Among these are nevi such as:
Melanomas grow in two distinct stages: radial and vertical. In the epidermis, malignant cells develop radially during the radial growth phase. Most melanomas advance to the vertical development phase over time, during which malignant cells infiltrate the dermis and acquire the ability to spread.
Classifications of melanomas are done according to their depth. Lesions under 1mm are classified as thin; between 1-4mm are moderate; larger than 4mm are thick.
Melanomas are classified according to their growth patterns. The 4 main types of melanomas are:
These account for approximately 70% of melanomas. They are usually flat but can become irregular and elevated in later stages. The lesions are about 2 cm in diameter and have a variety of colors, as well as external notches, indentations, or both.
They are responsible for 15-30% of melanoma diagnoses. Tumors caused are generally pigmented blue-black, but sometimes might be colorless.
These account for approximately 4-10% of melanomas, mostly resulting in tumors larger than 3cm. Beginning as small, freckle-like lesions; they develop into larger flat lesions with peripheral notching.
These are responsible for 2-8% melanomas in whit-skinned individuals, and 35-60% melanomas in black-skinned individuals. They commonly appear as flat, brown or tan stains on the palms with shapeless borders. Lesions near the toes or fingers are darker; brown or black, and often lead are accompanied with ulcerations in later stages of the disease.
5-10% patients have family history; the risk of affliction increases by 2.2 times if at least one relative has the disease. Physical characteristics such as blue eyes, red hair, pale complexion, or individuals easily burned by the sun have higher incidence rates of the disease.
Individuals with immunocompromised states such as patients with transplants, or hematological malignancies are more commonly affected. Patients with high exposure to UVB and UVA rays; especially those who wear sunscreen are more affected.
Recent evidence indicates that sunscreen blocks UVB radiations, so individuals are more exposed to UVA rays. Use of tanning beds, numbers of sunburns, and low latitude also increases incidence of melanomas.
A recent survey also found that individuals with a lower socioeconomic status have worse outcomes due to lower melanoma risk perception and lack of knowledge about the disease.
If any of your direct relatives (parents, brothers, sisters, or children) has had melanoma, your risk of developing it is increased. Around 10% of all melanoma patients have a family history of the disease.
A common family lifestyle of regular sun exposure, a family tendency to have pale skin, gene mutations that run in families, or a combination of these factors presents a higher risk of developing this condition.
Most specialists don’t recommend genetic testing to check for mutations that may increase risk in individuals with a family history of melanoma, because genetic testing is still not a reliable diagnostic tool for this condition.
Instead, experts recommend individuals with family history of melanoma to examine their skin regularly. Such individuals are also suggested to avoid facilities such as tanning beds (man-made UV exposure) and be cautious of sun exposure.
Factors that indicate a poor prognosis are:
Thickness of the tumor (worse outcomes with thicker lesions)
Tumor in regional lymph nodes indicates stage III of disease-
The stage of the disease during diagnosis greatly affects the prognosis. Patients diagnosed during the first stage have a 5-year survival rate of more than 90%; stage 2 patients have a 5-year survival rate between 45%-77%, and the 5-year survival rate for patients in the 3rd stage is between 27%-70%.
If the disease is discovered after metastasis has developed, the prognosis is generally very bleak. The average survival rate for such patients is below 20%.
https://www.cancer.org/cancer/melanoma-skin-cancer/causes-risks-prevention/risk-factors.htmlhttps://www.ncbi.nlm.nih.gov/books/NBK470409/
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Founded in 2014, medtigo is committed to providing high-quality, friendly physicians, transparent pricing, and a focus on building relationships and a lifestyle brand for medical professionals nationwide.
MASSACHUSETTS – USA
60 Roberts Drive, Suite 313,
North Adams, MA 01247
MAHARASHTRA – INDIA
7, Shree Krishna, 2nd Floor,
Opp Kiosk Koffee,
Shirole Lane, Off FC Road,
Pune 411004, Maharashtra
