Shrinkage of a pituitary metastasis of melanoma induced by pembrolizumab: a case report

Abstract Background Pituitary metastases are rare, often deriving from lung or breast cancer owing to the upper vena cava proximity. Pituitary metastases can manifest with signs and symptoms of pituitary tumors, consequent to mass effect (headache, visual impairment) and/or hormonal alterations (hyperprolactinemia, hypopituitarism, and diabetes insipidus). Immune checkpoint inhibitors burst immunity against tumors, significantly increasing patients’ survival, but their autoimmune side effects frequently involve the skin, the gastrointestinal tract, and the endocrine glands (pituitary, thyroid, pancreas). Case presentation A 77-year-old Caucasian man had undergone trans-nasal sphenoidal surgery for a nonsecreting pituitary macroadenoma in 2001, without remnant or endocrine deficits. In 2016, he was operated for a shoulder melanoma. In February 2018, imaging evaluation demonstrated metastases in lung, liver, and femur. Therefore, treatment with pembrolizumab (anti-programmed death 1) was scheduled in May 2018, but, before starting this therapy, a brain computed tomography performed for a sudden loss of consciousness detected a sellar mass of 17 × 12 mm, which extended to the pituitary stalk and compressed the optic chiasma. Focused magnetic resonance imaging confirmed the size and characteristics of the lesion, while emergency evaluation of the hormonal profile demonstrated an impairment of adrenal and thyroid function. The pituitary lesion demonstrated a remarkable shrinkage (8 × 6 mm), which was confirmed by subsequent imaging evaluations. Conclusions This is the first case reporting on effectiveness of immune checkpoint inhibitors in a patient with pituitary metastasis from a melanoma.

Download Full-text

Bluish-gray fingernail discoloration due to the use of nivolumab

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220929974 ◽

2020 ◽

pp. 107815522092997

Author(s):

Miguel Michel Ocampo ◽

Jaren Lerner ◽

Constantin A Dasanu

Keyword(s):

Case Report ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Skin Toxicity ◽

Unique Case ◽

First Case ◽

Nail Discoloration ◽

Wide Range ◽

Causality Relationship

Introduction Immune checkpoint inhibitors have improved clinical outcomes in a wide range of cancers. While skin toxicity is not uncommon with immune checkpoint inhibitors, generalized nail discoloration has not been reported with their use in oncology. Case report Herein, we report a unique case of bluish-gray fingernail discoloration due to nivolumab therapy for relapsed melanoma. Management and outcome: This condition reversed completely 10 weeks after nivolumab discontinuation. Naranjo nomogram assessment renders the causality relationship between nivolumab and nail discoloration probable. Discussion To our knowledge, this is the first case report of an unusual bluish-gray nail discoloration due to therapy with nivolumab. The mechanism by which nivolumab causes this side effect remains to be elucidated.

Download Full-text

Some aspects of nivolumab administration in treatment for metastatic melanoma (clinical cases)

Medical Council ◽

10.21518/2079-701x-2021-9-64-74 ◽

2021 ◽

pp. 64-74

Author(s):

L. Yu. Vladimirova ◽

A. Eh. Storozhakova ◽

I. L. Popova ◽

S. N. Kabanov ◽

N. A. Abramova ◽

...

Keyword(s):

Clinical Trials ◽

Brain Metastases ◽

Metastatic Melanoma ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Skin Toxicity ◽

Complete Regression ◽

Cutaneous Toxicity ◽

First Case

The development of a new direction in anticancer medical therapy – the use of immune checkpoint inhibitors targeting PD-1/ PD-L1 and CTLA-4 – has significantly changed the approach to tumor treatment in the last few years. The PD1 blocker nivolumab in major registered clinical trials improved overall survival, including in metastatic melanoma, with a favorable toxicity profile. However, its efficacy in patients with brain metastases from melanoma was poorly studied, since the inclusion criteria for most clinical trials do not envisage recruiting such patients. The immune-mediated toxicity of immune checkpoint inhibitors is currently well enough studied. However, cases of cutaneous toxicity are quite rare and present certain difficulties for differential diagnosis and treatment. This article presents two cases of effective nivolumab treatment in patients with generalized BRAFwt and BRAFmut cutaneous melanoma. The first case is of interest due to the presence of brain metastases in the patient. Nivolumab therapy helped achieving complete regression of intracranial metastases with the long-term effect. The second case, in addition to effective treatment, demonstrates a rare manifestation of skin toxicity – vitiligo on the face and upper extremities.

Download Full-text

Acute motor axonal neuropathy after ipilimumab and nivolumab treatment in melanoma brain metastases: A case report and review of the literature

SAGE Open Medical Case Reports ◽

10.1177/2050313x211042215 ◽

2021 ◽

Vol 9 ◽

pp. 2050313X2110422

Author(s):

Yolanda Piña ◽

Brittany R. Evernden ◽

Nikhil Khushalani ◽

Kim Margolin ◽

Hussein Tawbi ◽

...

Keyword(s):

Brain Metastasis ◽

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Axonal Neuropathy ◽

Braf V600e ◽

Acute Motor Axonal Neuropathy ◽

Melanoma Brain Metastasis ◽

First Case

The use of immune checkpoint inhibitors including ipilimumab and nivolumab has expanded for several tumors including melanoma brain metastasis. These have resulted in a growing spectrum of neurologic immune-related adverse events, including ones that are rare and difficult to diagnose and treat. Here, we present a patient with melanoma brain metastasis who was treated with immune checkpoint inhibitors and developed an Acute Motor Axonal Neuropathy. To our knowledge, this is the first case of Acute Motor Axonal Neuropathy as an immune-related adverse event associated with combination treatment of ipilimumab and nivolumab, who was successfully treated. A 28-year-old woman with metastatic BRAF V600E melanoma developed melanoma brain metastasis and was enrolled on Checkmate 204, a Phase 2 clinical trial using ipilimumab (3 mg/kg intravenous) and nivolumab (1 mg/kg intravenous) every 3 weeks for four cycles, followed by monotherapy with nivolumab (240 mg intravenous) every 2 weeks. A few days after Cycle 2 of ipilimumab and nivolumab, she developed a pure motor axonal neuropathy consistent with Acute Motor Axonal Neuropathy. She was treated with several immunosuppressive treatments including high dose methylprednisolone, immune globulin, and infliximab, and her motor neuropathy eventually improved several months after onset of symptoms. Unfortunately, she had progression of her systemic disease and died several months later. This is the first case reported of Acute Motor Axonal Neuropathy associated with ipilimumab and nivolumab, successfully treated with immune-suppressive therapy. As the field of immunotherapy expands with the increasing use of the immune checkpoint inhibitors, it is critical to increase our knowledge and understanding of the neurologic immune-related adverse events associated with immune checkpoint inhibitors. This includes the spectrum of rare neurologic immune-related adverse events, which can be quite difficult to recognize and treat. Early consultations with neurology may expedite a diagnosis and treatment plan in patients with unexplained weakness receiving immune checkpoint inhibitor therapy.

Download Full-text

Demyelinating disease of the central nervous system associated with Pembrolizumab treatment for metastatic melanoma

Multiple Sclerosis Journal ◽

10.1177/1352458518803724 ◽

2018 ◽

Vol 25 (7) ◽

pp. 1005-1008 ◽

Cited By ~ 6

Author(s):

João Durães ◽

Inês Coutinho ◽

Angelina Mariano ◽

Argemiro Geraldo ◽

Maria Carmo Macário

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Metastatic Melanoma ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Demyelinating Disease ◽

Checkpoint Inhibitors ◽

Causative Role ◽

First Case ◽

The Central Nervous System

Immune checkpoint inhibitors are used in metastatic melanoma with good efficacy and safety profile. We report the first case of an inflammatory demyelinating disease of the central nervous system during treatment with Pembrolizumab and discuss the evidence in the literature supporting its causative role. The patient had a good clinical recovery after intravenous steroids, plasma exchange and discontinuation of Pembrolizumab. Due to the expected increase in the importance of immune checkpoint inhibitors in cancer treatment, it is important to be aware of neurological adverse events, as early treatment usually leads to good clinical responses.

Download Full-text

SAT-116 An Affair of the Heart - First Case Report of Immune Checkpoint Inhibitor Associated Cardiac Sarcoidosis Presenting with Non-PTH Medicated Hypercalcemia

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1099 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Jonven Attia ◽

Bruce Goldman ◽

Deepak Sahasrabudhe ◽

Eugene Storozynsky ◽

Inga Harbuz-Miller

Keyword(s):

Case Report ◽

Adverse Effects ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Cardiac Sarcoidosis ◽

Checkpoint Inhibitors ◽

Early Recognition ◽

Mediastinal Lymph Node ◽

Single Agent ◽

First Case

Abstract Background: Immune checkpoint inhibitors (ICI) are an effective new tool in the treatment of malignancy by rescuing exhausted T-cells and enhancing anti-tumor immunity. The offset of immune self-tolerance can result in autoimmune adverse effects involving gastrointestinal, pulmonary and endocrine systems. Lung and skin sarcoidosis have been described in association with ICI use. We present the first case of non-PTH medicated hypercalcemia due to cardiac sarcoidosis in the setting of immunotherapy. Case Presentation: A 71-year-old man was referred to endocrinology for hypercalcemia. He had a fourteen-year history of scalp melanoma in remission until February 2019, when routine surveillance scans suggested metastatic disease. Computer tomography of the chest showed mediastinal and hilar lymphadenopathy (largest node 5.2 cm) and numerous pulmonary nodules (largest 1.7 cm). Biopsy of the largest pulmonary nodule and mediastinal lymph node (LN) confirmed BRAF wild-type metastatic melanoma. Ipilimumab/nivolumab (antiCTLA4/antiPD-1) combination therapy was started. After two cycles, hypercalcemia was noted on routine laboratory surveillance. He was asymptomatic and physical exam was unremarkable. Initial workup revealed: calcium 10.6 mg/dL (8.6-10.2), albumin 4 g/dL (3.5 - 5.2), phosphorus 3.8 mg/dL (2.7 - 4.5), PTH <0.6 pg/mL (15.0 - 65.0), PTHrP <2.0 pmol/L (0.0 - 2.3), 25 hydroxyvitamin D 22. 9 ng/mL (30 - 60), vitamin A 0.59 mg/L (0.30 - 1.20). He denied taking calcium-containing supplements. He was treated with hydration and immunotherapy was continued for two cycles, followed by single agent nivolumab. After three months on ICI, the metastatic lesions were reduced in size by 30%. His calcium peaked at 12.5 mg/dL and was treated with 4mg of intravenous Zoledronic acid without resolution. He developed worsening functional status, symptomatic hypotension, and elevated troponins. Cardiac MRI demonstrated myocarditis and nivolumab-induced myocarditis was suspected. Surprisingly, endomyocardial biopsy revealed multiple granulomas suggestive of sarcoidosis. AFB, PAS and Congo red stains were negative. He was treated with supportive care and glucocorticoids with resolution of hypercalcemia and improved cardiac function. Unfortunately, serum 1,25 dihydroxy vitamin D was not successfully measured until after the first dose of prednisone and was found at the upper limit of our reference range 62.0 pg/mL (19.9-79.3). Conclusion: Immune checkpoint inhibitors are effective agents in treating various cancers. Adverse effects due to autoimmunity are common and early recognition of life-threatening complications is critical. Although cutaneous and pulmonary sarcoidosis have been described with ICI, to our knowledge, this is the first case report of ICI-related cardiac sarcoidosis presenting with PTH-independent hypercalcemia.

Download Full-text