Anti-PD-1 Antibodies Linked To Side Effects Throughout The Body

Patient symptoms during programmed cell death 1 treatment should be considered as potential immune-relate adverse events

medwireNews: Physicians should have a high level of suspicion for immune-related adverse events (irAEs) in patients during pembrolizumab or nivolumab treatment, say the authors of two studies showing that anti-programmed cell death 1 (anti-PD-1) antibodies may affect all organ systems.

“Medical staff as well as patients and their families have to be well informed about potential side-effects”, say Lucie Heinzerling, from University Hospital Erlangen in Germany, and co-authors of the two articles published in the European Journal of Cancer.

“Since irAEs can start asymptomatic or with minimal symptoms, careful monitoring with laboratory assessments is essential”, they emphasize. “If symptoms are autoimmune-related, prompt treatment including high-dose corticosteroids can be necessary.”

The researchers identified 242 irAEs in 138 of 496 metastatic melanoma patients attending 15 skin cancer centres for pembrolizumab or nivolumab therapy.

The first study describes irAEs affecting the respiratory tract, musculoskeletal system and nervous system, reported in 24, 21 and 16 patients, respectively.

Respiratory irAEs included eight cases of autoimmune-related pneumonitis, seven of cough and four of dyspnoea, while voice changes were noted in one patient.

Eight patients experienced arthralgia and seven had myositis or myalgia, affecting walking or quality of life. Muscle spasms, polymyalgia rheumatica, synovitis and exacerbation of psoriasis arthritis were also reported in one or two patients.

Nervous system irAEs included paraesthesia, paresis/paralysis, polyneuropathy, seizures, Guillain-Barré syndrome (alone or alongside polyradiculitis), the researchers say.

In addition, five patients experienced eight cardiac irAEs, including one patient with atrial flutter and left ventricular systolic dysfunction who was diagnosed with myocarditis and cardiomyopathy at autopsy. Sinus tachycardia, hypertension, stable angina pectoris and sudden asystolia were each reported in one patient.

Meanwhile, 15 patients had constitutional or infectious irAEs, such as fever or pneumonia, eight experienced ocular irAEs, including dry eye, uveitis and blurred vision. Two patients had anaemia and one patient leucopenia.

The researchers note that most irAEs were grade 1 or 2 but recommend: “Treatment with anti-PD-1 antibodies should be paused when AEs are severe, but can often be resumed as documented in our study. If side-effects are life-threatening, anti-PD-1 treatment has to be discontinued.”

The second study, also by Lucie Heinzerling and co-authors, described skin, gastrointestinal, liver, endocrine and renal irAEs in the same patient population. Dermatological irAEs were reported in 43 patients, and included common grade 1 or 2 events like pruritus and rash, vitiligo and alopecia, as well as grade 3 lichenoid and cytotoxic reactions.

Thirty patients experienced irAEs affecting the endocrine system, including hypothyroidism, hyperthyroidism, hypophysitis and adrenal insufficiency. In addition, four patients developed diabetes mellitus Type 3 requiring insulin replacement.

Gastrointestinal irAEs affected 21 patients, most commonly diarrhoea, abdominal pain, coprostasis and xerostomia, with colitis reported in two and oesophagitis in one patient. All but four cases of grade 3 diarrhoea were mild.

A further 11 patients developed grade 3 or 4 hepatitis, nine patients grade 2 to 4 pancreatitis, one of whom has persistent pancreas insufficiency, and two patients experienced three cases of renal failure and nephritis.


Zimmer L, Goldinger SM, Hofmann L, et al. Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy. Eur J Cancer 2016; Advance online publication 13 April. doi:10.1016/j.ejca.2016.02.024

Hofmann L, Forschner A, Loquai C, et al. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. Eur J Cancer 2016; Advance online publication 13 April. doi:10.1016/j.ejca.2016.02.025

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