Table 3. Anti PD-1/PD-L1 therapy induced autoimmune diabetes mellitus.
| Disease | Other medical history | Agent and dose | Time of hyper-glycemia occur | DKA | C-peptide | HbA1c | Relative auto-antibody | Glucocorticoid (outcome)* | Other adverse effect | Reference |
|---|---|---|---|---|---|---|---|---|---|---|
| Melanoma | NA | Pembrolizumab 2 mg/kg q3w | After the 7th cycle | + | <0.01 ìg/L | NA | Anti-GAD(−), ICA(−), anti-TPO(−) | NA | Hypothyroidism (after the 5th cycle) | (14) |
| NSCLC | NA | Pembrolizumab 2 mg/kg q3w | After the 3rd cycle | + | 0.51 ng/mL | 8% | Anti-GAD(−), ICA(−), IAA(−) | NA | NA | (13) |
| Lung adenocarcinoma | NA | Pembrolizumab, carboplatin, nab-paclitaxel | After the 2nd cycle | − | 0.81 ng/mL (further decreased to <0.10 ng/mL) | 5.80% | Anti-GAD 23.8 U/mL, anti-IA2 0.32 nmol/L | Prednisone (no improvement in glycemic control) | NA | (19) |
| Urothelial carcinoma | NA | Pembrolizumab 200 mg q3w | After the 3rd cycle | + | Undetectably | 6.70% | Anti-GAD(−) | NA | NA | (20) |
| Lung adenocarcinoma | COPD, sleep apnea syndrome, hyperlipidemia | Pembrolizumab 200 mg q3w | After the 8th cycle | + | 0.1 ng/mL | 8.40% | Anti-GAD(−) | NA | Destructive thyroiditis (before the 3rd cycle) | (21) |
| Melanoma | NA | Pembrolizumab 2 mg/kg | After the 2nd cycle | + | 57 pmol/L | 7.10% | Anti-GAD(−), IA-2(−) | Prednisolone (insulin resistance) |
Mild thyroid dysfunction | (22) |
| NSCLC | NA | Pembrolizumab | After 8 weeks | + | 0.02 nmol/L | NA | Anti-GAD >171 U/mL | NA | Thyroiditis | (23) |
| NSCLC | NA | Nivolumab 3 mg/kg q2w | After the 2nd cycle | + | <0.1 ng/mL | 7.10% | Anti-GAD(+), IA-2(+), IAA(+) (further examination found anti-GAD and IA-2 was positive before nivolumab treatment) | NA | Subclinical hyperthyroidism | (16) |
| Melanoma | Dyslipidemia, Grave’s disease (due to IFNα adjuvant therapy before) | Nivolumab 3 mg/kg q2w | After the 3rd cycle | + | Undetectably | 8.80% | Anti-GAD(+), IA-2(+), ZnT8A(+) (retrospective study found that these antibodies were positive 3 month before nivolumab treatment) | NA | NA | (17) |
| Lung squamous cell carcinoma | T2DM, COPD, hypertension, hypercholesterolemia | Nivolumab 3mg/kg q2w | After the 1st cycle | + | <0.1 ng/mL | 7.60% | Anti-GAD(+) | NA | NA | (15) |
| Lung adenocarcinoma | NA | Nivolumab 3mg/kg q2w | After the 11th cycle | − | 0.97 ng/mL | 9.40% | Anti-GAD(−), IA-2(−), IAA(−), ZnT8A(−) | NA | Exacerbation of pneumonitis, vitiligo | (24) |
| Melanoma | Grave’s disease | Nivolumab 3 mg/kg q3w | After the 27th cycle | + | 0.2 nmol/L | 8.20% | Anti-GAD(−), ICA(−), IA-2(−), IAA(−), Zn8TA(−) | NA | Thrombo-phlebitis | (25) |
| Renal cell carcinoma | NA | Nivolumab 3 mg/kg q2w | after the 6th cycle | − | 5.92 ng/mL (further decreased to <0.3 ng/mL) | 6.20% | Anti-GAD(−), IAA(−), IA-2(−), Zn8TA(−) | NA | NA | (26) |
| Merkel cell carcinoma | NA | Avelumab 523 mg q2w | after the 10th cycle | − | 1.07 ng/mL (further decreased to 0.08 ng/mL) | 7.50% | Anti-GAD(−), IA-2(−) | NA | NA | (18) |
*, try to use steroid to reverse the autoimmune diabetes mellitus. DKA, diabetic ketoacidosis; HbA1c, glycosylated hemoglobin; NSCLC, non-small cell lung cancer; COPD, chronic obstructive pulmonary disease; GAD, glutamic acid decarboxylase; ICA, islet cell antibodies; IA-2, tyrosine phosphatase-related islet antigen 2; IAA, insulin antibodies; ZnT8A, zinc transporter 8 antibodies; TPO, thyroid peroxidase; IFNα, interferon α.