Pembrolizumab induced Lichen Planopilaris

A New Case of Pembrolizumab induced Lichen Planopilaris

Authors of a new study present of a patient who developed the scarring alopecia known as lichen planopilaris while undergoing treatment with the anti programmed cell death receptor-1 (anti-PD-1) drug pembrolizumab for metastatic melanoma. Pembrolizumab is known as an “immune checkpoint inhibitor.” We’ll spend some time looking at this important class of drugs.

A Closer Look at Immune Checkpoints and Immune Checkpoint Inhibitors

In order to better understand what Pemrolizumab is and what it does, we need to understand the concept of ‘immune checkpoints’.

Immune ‘checkpoints’ are a normal part of the immune system. The role of these checkpoints is to prevent an immune system response from being so strong that it destroys healthy cells inside in the body.

Proteins on the surface of T cells (called immune checkpoint proteins) can bind proteins on the surface of cancer cells (called partner proteins). When T cell checkpoint proteins engage with these partner proteins, the T cell is ultimately sent a signal to “settle down” and not proceed to kill the cell it is bound to. This is not good when it comes to cancer as it prevents the T cell from killing the cancer cell.

New drugs known as immune checkpoint inhibitors act to blocking checkpoint proteins from binding with their partner proteins. Some checkpoint inhibitors also bind to the partner protein to prevent the interaction. All in all, this prevents the T cell from being told to ‘settle down’ and the results is the T cell then proceeds to kill the cancer cell.

Ipilimumab: The first FDA approved checkpoint inhibitor

The first immune checkpoint inhibitor was approved by the Food and Drug Administration in 2011. It is an antibody targeting the cytotoxic T lymphocyte antigen 4 (CTLA4). The drug is known as ipilimumab and was approved in 2011 for treatment of melanoma. To date, there are numerous checkpoint inhibitor drugs approved and being studied. Some are summarized below:

What is Pembrolizumab ?

Pembrolizumab is a drug that blocks PD-1 on T cells. PD-1 blockade allows for the immune system to become activated and then allows for the production of antibodies directed at tumor antigens.

What is Pemrolizumab FDA approved for?

Pemrolizumab is FDA approved for breast cancer, cervical cancer, colorectal cancer, skin squamous cell carcinoma, endometrial carcinoma, esophageal carcinoma, gastric carcinoma, liver cancer (HCC), Hodgkin lymphoma (HL) and large B cell lymphoma, head and neck squamous cell carinoma, melanoma, mesothelioma, merkel cell carinoma, lung cancer (NSCLC and SCLC), , renal cell carcinoma, urothelial carcinoma and others

Why do immune checkpoint inhibitors increase the risk of autoimmune reactions?

Immune activation may also lead to production of antibodies against self-antigens. Therefore, checkpoint inhibition can induce autoimmune responses, generating immune-related adverse events.

What is known about “lichenoid” skin reaction with anti-PD-1 drugs?

Lichenoid skin reactions are common immune-related adverse skin reactions and are observed in 17.1% of patients treated with PD-1 inhibitors. Lichenoid reactions mainly affect the skin and mucosae but they have been rarely reported to affect the hair too. Lichen planus, hypertrophic lichen planus, lichen planus pemphigoides, lichenoid dermatitis and lichen planopilaris have all been reported in several publication after use of checkpoint inhibitors.

What is known about LPP with anti-PD-1 drugs?

Lichen planopilaris has been reported after use of checkpoint inhibitor drugs including these prior studies:

STUDY 1. Uthayakumar AK et al. Severe progressive scarring pembrolizumab-induced lichen planopilaris in a patient with metastatic melanoma. Australas J Dermatol. 2021 Aug;62(3):403-406.

STUDY 2. Cogen et al. Lichen planopilaris associated with pembrolizumab in a patient with metastatic melanoma. JAAD Case Rep . 2018 Jan 16;4(2):132-134.

STUDY 3. Dominguez-Santas M et al. Avelumab-induced lichen planopilaris, a novel association. Int J Dermatol. 2021 Oct;60(10):e414-e416.

Garcia-Melendo C et al, 2022

Garcia-Melendo and colleagues presented another case in an accumulating list of cases of LPP after use of PD1 inhibitors. The patient was a 62-year-old Caucasian man was diagnosed with stage IIB melanoma on his back in 2009. In 2017, he developed a skin relapse, lymph node progression and a brain metastasis. He underwent surgery of the skin lesion, lymph node dissection and also whole brain radiation. The patient did not experience radiodermitis or any type of radiotherapy-induced alopecia. Since the brain lesion remained unchanged, pembrolizumab was administered. After the second infusion, he presented with intense pruritus and scalp desquamation. After 16 weeks of the drug, significant hair shedding occurred accompanied by numerous follicular keratotic papules on the entire scalp and severe erythema. A biopsy revealed findings consistent with lichen planopilaris.

The patient was treated with the class 1 steroid clobetasol propionate 0.05% lotion once daily with complete resolution of the scalp itching within a matter of 2 weeks and was able to continue the pembrolizumab therapy for his melanoma. Although the redness settled, he was left with some degree of permanent scarring alopecia.

COMMENTS

This is at least the third report of LPP developing after use of pembrolizumab. The mechanisms are not clear but it was proposed that there may have been similar antigens on the tumor cells as in the hair follicles. The authors proposed that the patient’s radiation treatment could have exposed the immune system to skin and hair follicle antigens in some way that then facilitated the development of LPP with pembrolizumab.

It’s not clear why this reaction happens but it is important to recognize as the condition may settle readily at least in some cases with minimal therapies like topical clobetasol.

REFERENCE

Garcia-Melendo C, et al. Extensive lichen planopilaris as exclusive lichenoid reaction secondary to pembrolizumab in a patient with metastatic melanoma. Dermatol Ther. 2022 Feb 17;e15388.

ADDITIONAL REFERENCES

Uthayakumar AK et al .Severe progressive scarring pembrolizumab-induced lichen planopilaris in a patient with metastatic melanoma. Australas J Dermatol. 2021 Aug;62(3):403-406.

Cogen et al. Lichen planopilaris associated with pembrolizumab in a patient with metastatic melanoma. JAAD Case Rep . 2018 Jan 16;4(2):132-134.

Dominguez-Santas M et al. Avelumab-induced lichen planopilaris, a novel association. Int J Dermatol. 2021 Oct;60(10):e414-e416.