Keytruda Disease Interactions

Pembrolizumab can cause immune-mediated adverse reactions, which may be severe or fatal. Immune-mediated adverse reactions can occur in any organ system or tissue, can affect more than 1 body system simultaneously, and can occur at any time after starting therapy. Care should be exercised when using pembrolizumab in patients with preexisting immune system disorders (e.g., ulcerative colitis, Crohn's disease, lupus) or with conditions affecting the nervous system (e.g., myasthenia gravis, Guillain-Barre syndrome). It is recommended to monitor patients closely for signs/symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Liver enzymes, creatinine, and thyroid function should be evaluated at baseline and periodically during therapy. For patients with triple-negative breast cancer treated with pembrolizumab in the neoadjuvant setting, blood cortisol should be monitored at baseline, before surgery, and as clinically indicated. If immune-mediated adverse reactions are suspected, appropriate workup should be started to exclude alternative etiologies (including infection). Medical management should be started promptly, including specialty consultation as appropriate. Pembrolizumab should be withheld or permanently discontinued depending on severity.

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a programmed death receptor-1/ligand-1 (PD-1/PD-L1) blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. It is recommended to follow patients closely for evidence of transplant-related complications and intervene promptly. The benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody before or after an allogeneic HSCT should be considered.

Myasthenic syndrome/myasthenia gravis (including exacerbation) has been reported with the use of programmed death receptor-1/ligand-1 (PD-1/PD-L1) blocking antibodies. Care should be exercised when using PD-1/PD-L1 blocking antibodies in patients with myasthenia gravis.

Solid organ transplant rejection and other transplant (including corneal graft) rejection have been reported with the use of programmed death receptor-1/ligand-1 (PD-1/PD-L1) blocking antibodies. Care should be exercised when using PD-1/PD-L1 blocking antibodies in patients who have received a solid organ or other transplant.

Pembrolizumab can cause immune-mediated colitis, which may present with diarrhea. CMV infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis; repeating infectious workup should be considered in these patients to exclude alternative etiologies. Pembrolizumab should be withheld or permanently discontinued depending on severity of colitis.

Pembrolizumab can cause immune-mediated hepatitis. Pembrolizumab in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of grades 3 and 4 ALT and AST elevations compared to pembrolizumab alone. Liver enzymes should be monitored before starting and periodically during therapy; more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents should be considered. Pembrolizumab should be withheld or permanently discontinued depending on severity of hepatitis.

Mild liver dysfunction (total bilirubin up to the upper limit of normal [ULN] and AST greater than ULN or total bilirubin greater than 1 to 1.5 times ULN and any AST) had no clinically significant effect on the clearance of pembrolizumab. The effect of moderate or severe liver dysfunction on the pharmacokinetics of pembrolizumab is unknown. Care should be exercised when using pembrolizumab in patients with liver dysfunction.

The use of pembrolizumab in combination with a thalidomide analog plus dexamethasone is not recommended in patients with multiple myeloma outside of controlled trials. In 2 randomized trials in patients with multiple myeloma, the addition of pembrolizumab to a thalidomide analog plus dexamethasone, a use for which no programmed death receptor-1 or programmed death ligand-1 (PD-1 or PD-L1) blocking antibody is indicated, resulted in increased mortality.

Pembrolizumab can cause immune-mediated pneumonitis; fatal cases have been reported. In general, the incidence of pneumonitis was higher in patients with prior thoracic radiation. Care should be exercised when using pembrolizumab in patients with preexisting pulmonary impairment and in those who have received thoracic radiation. Pembrolizumab should be withheld or permanently discontinued depending on severity of pneumonitis.

Pembrolizumab can cause immune-mediated thyroid disorders. Thyroid function should be evaluated at baseline and periodically during therapy. It is recommended to initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Pembrolizumab should be withheld or permanently discontinued depending on severity. Care should be exercised when using pembrolizumab in patients with thyroid disease.