Nivolumab

PD-1 monoclonal antibody used for the treatment of non-resectable or metastatic malignant melanoma and locally advanced or metastatic non-small cell lung cancer (NSCLC).

Nivolumab binds to the PD-1 receptor (Programmed Death Receptor 1) on T cells and thus stimulates the immune system. For further information see PD-1 antibody below

Metastatic malignant melanoma:

The overall response rate in metastatic malignant melanoma was 43.7% with nivolumab monotherapy. Progression-free survival was 2.9 months. This therapeutic success was significantly improved by the simultaneous administration of nivolumab and the CTLA-4 antibody ipilimumab (CheckMate 069 study). Both checkpoint inhibitors act independently of each other, so that a synergistic effect can be assumed when used together.

In a further Phase III trial, the combination of nivolumab and ipilimumab led to longer progression-free survival and a higher objective response rate in patients with advanced melanoma than under the monotherapy with ipilimumab (Wolchok et al. 2017).

Very common (≥ 1/10): Fatigue, rash, pruritus, diarrhea, nausea, neutropenia, elevated AST, elevated ALT, alkaline phosphatase elevation, lipase elevation, amylase elevation, hypokalemia, creatinine elevation, hyperglycemia, lymphopenia, leukopenia, thrombocytopenia, anemia, hypercalcemia, hyperkalemia, hypokalemia, hypomagnesemia, and hyponatremia

Common (≥ 1/100, < 1/10): Upper respiratory tract infections, infusion-related reactions, hypersensitivity, hypothyroidism, hyperthyroidism, decreased appetite, peripheral neuropathy, headache, dizziness, hypertension, pneumonitis, dyspnea, cough, colitis, stomatitis, vomiting, abdominal pain, Constipation, dry mouth, vitiligo, dry skin, erythema, alopecia, musculoskeletal pain, arthralgia, pyrexia, edema (including peripheral edema), increase in total bilirubin, hypoglycemia, hypermagnesemia, hypernatremia, and weight loss.

Occasional (≥ 1/1,000, < 1/100): Pneumonia, bronchitis, adrenal insufficiency, hypopituitarism, thyroiditis, diabetes mellitus, dehydration, metabolic acidosis, hepatitis, polyneuropathy, autoimmune neuropathy (including facial nerve and abducens palsy), uveitis, blurred vision, dry eyes, Tachycardia, pleural effusion, pancreatitis, gastritis, erythema multiforme, psoriasis, rosacea, urticaria, rheumatoid polymyalgia, arthritis, tubulointerstitial nephritis, renal failure (including acute renal failure), chest pain and tenderness (^OPDIVO® SmPC).

Furthermore, maculopapular, psoriasiform, lichenoid, and in rarer cases autoimmune bullous exanthema (see below Lichen ruber pemphigoides) and vitiligo have been reported (Mueller KA et al. 2021).

Opdivo®

In a phase III study, 906 patients were treated with either intravenous nivolumab (3mg/kgkgkgKG every 2 weeks) or ipilimumab (10mg/kgKG every 3 weeks over 4 doses and then every 2 weeks) after complete resection of stage IIIB and IIIC or IV melanoma. the patients were treated for a period of 1 year or until the occurrence of recurrence or unacceptable toxicity. The direct comparison showed a significant longer survival in the nivolumab-treated group with better tolerability (Weber J et al 2017).

1. Mehta A et al (2016) Myocarditis as an immune-related adverse event with ipilimumab/nivolumab combination therapy for metastatic melanoma. Melanoma Res 26:319-320.

2. Mueller KA et al (2021) A case of severe nivolumab-induced lichen planus pemphigoides in a child with metastatic spitzoid melanoma. Pediatr Dermatol 40: 154-156.

3. OPDIVO® SmPC /Summary of product characteristics. https://fi.b-ms.de/Opdivo.

4. Postow MA et al (2015) Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 372:2006-2017.

5. Sibaud Vet al (2016) Dermatologic complications of anti-PD-1/PD-L1 immune checkpoint antibodies. Curr Opin Oncol PubMed PMID: 27136138.
6. Weber JS et al (2013) Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. J Clin Oncol 31: 4311-4318.
7. Weber J et al (2017) Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma.N Engl J Med 377:1824-1835.
8. Wolchok JD et al.(2017) Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med 377:1345-1356.