Atezolizumab/hyaluronidase Disease Interactions

Immune-related thyroid disorders, adrenal insufficiency, and type 1 diabetes mellitus, including diabetic ketoacidosis, have been reported in patients receiving atezolizumab. It is recommended to monitor patients for clinical signs and symptoms of endocrinopathies and to institute appropriate measures as necessary. Monitor as clinically indicated prior to and periodically during treatment and withhold, reduce dose, or discontinue therapy as necessary.

Immune-mediated hepatitis occurred in patients receiving atezolizumab treatment with reported liver test abnormalities. Monitor patients for liver function test and for symptoms of hepatitis. Monitor bilirubin prior to and periodically during treatment. Therapy with atezolizumab should be administered cautiously in these patients. It is recommended to withhold atezolizumab for Grade 2 immune-mediated hepatitis and institute appropriate measures and to permanently discontinue therapy for Grade or 4 immune-mediated hepatitis

Severe infections, including urinary tract infections, pneumonia, sepsis, herpes encephalitis, and mycobacterial infection leading to retroperitoneal hemorrhage occurred in patients treated with atezolizumab. It is recommended to monitor patients for signs and symptoms of infection and to treat with antibiotics for suspected or confirmed bacterial infections. Withhold therapy for greater than or equal to Grade 3 infections.

Immune-related meningoencephalitis has been reported with the use of atezolizumab therapy. Monitor patients for clinical signs and symptoms of meningitis or encephalitis. Permanently discontinue therapy for any grade of meningitis or encephalitis.

Immune-related myasthenic syndrome/myasthenia gravis, Guillain-Barré, and ocular inflammatory toxicity have been reported with the use of atezolizumab therapy. Monitor patients for symptoms of motor and sensory neuropathy. Permanently discontinue therapy for any grade of myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome and institute medical intervention as appropriate.

Immune-related pancreatitis, including increases in serum amylase and lipase levels have been reported with the use of atezolizumab therapy. Caution is recommended and patients should be monitored for signs and symptoms of acute pancreatitis. Withhold atezolizumab for greater than or equal to Grade 3 serum amylase or lipase levels (> 2.0 ULN), or Grade 2 or 3 pancreatitis and permanently discontinue therapy for Grade 4 or any grade of recurrent pancreatitis.

Immune-mediated colitis or diarrhea have been reported during atezolizumab therapy, in some cases with fatal outcomes. Monitor patients for signs and symptoms of diarrhea or colitis. It is recommended to withhold treatment with atezolizumab for Grade 2 diarrhea or colitis and if symptoms persist for longer than 5 days or recur, it is recommended to administer 1 to 2 mg/kg prednisone or equivalent per day. Withhold treatment for Grade 3 diarrhea or colitis and treat with IV methylprednisolone 1 to 2 mg/kg per day and convert to oral steroids once the patient has improved. For both Grade 2 and Grade 3 diarrhea or colitis, when symptoms improve to Grade 0 or Grade 1, taper steroids over greater than or equal to 1 month. Resume treatment if the event improves to Grade 0 or 1 within 12 weeks and corticosteroids have been reduced to the equivalent of less than or equal to 10 mg oral prednisone per day. Permanently discontinue atezolizumab for Grade 4 diarrhea or colitis.

Population pharmacokinetic analyses suggest that no dose adjustment of atezolizumab is needed for patients with mild hepatic impairment. No clinical studies were conducted with atezolizumab in patients with moderate or severe hepatic impairment. Caution is recommended when using this agent.

Immune-mediated pneumonitis, sometimes fatal, or interstitial lung disease have been reported during atezolizumab therapy. Patients should be monitored with radiographic imaging and for symptoms of pneumonitis. Therapy with atezolizumab should be administered cautiously in patients with or predisposed to pulmonary dysfunction. It is recommended to withhold atezolizumab until resolution for Grade 2 pneumonitis and to permanently discontinue therapy for Grade 3 or 4 pneumonitis.

Population pharmacokinetic analyses suggest that no dose adjustment of atezolizumab is required for patients with renal impairment. The effect of severe renal impairment on the pharmacokinetics of atezolizumab is unknown. Caution is recommended with these patients.

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.