Case of type 1 diabetes associated with less‐dose nivolumab therapy in a melanoma patient

Teramoto, Yukiko; Nakamura, Yasuhiro; Asami, Yuri; Imamura, Taichi; Shuji, Takahira; Nemoto, Manabu; Sakai, Gota; Shimada, Akira; Noda, Mitsuhiko; Yamamoto, Akifumi

doi:10.1111/1346-8138.13486

Cited by 43 publications

(13 citation statements)

References 5 publications

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“…The two cases reported here describe the development of late-onset, insulin-dependent, autoimmune diabetes mellitus (i.e., T1DM) in association with the administration of both anti-PD-1 and anti-PD-L1 immune checkpoint inhibitors. Upon review of the literature, our first patient appears to be the 12th reported case of T1DM associated with the administration of nivolumab (anti-PD-1), while our second patient appears to be the first reported case of T1DM associated with the administration of atezolizumab (anti-PD-L1) (Table 2 ) [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”

Section: Discussionmentioning

confidence: 95%

“…Indeed, there are several reports in animal models that mechanistically demonstrate that either genetic deletion or pharmacological inhibition of these immune checkpoint molecules (PD-1 and PD-L1) enhance the rate and incidence of autoimmune diabetes [ 3 , 4 , 5 , 6 ]. While there are multiple reports that describe a temporal association between the use of PD-1 inhibitors for tumor therapy and the rapid induction of a late-onset autoimmune diabetes mellitus [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ], only two reports to date associate PD-L1 inhibitors with diabetes mellitus (BMS-936559 [ 18 ] and an unspecified PD-L1 inhibitor [ 13 ]).…”

Section: Introductionmentioning

confidence: 99%

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Immune Checkpoint Inhibitor-Associated Type 1 Diabetes Mellitus: Case Series, Review of the Literature, and Optimal Management

et al. 2017

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With the introduction of immune checkpoint inhibitors into clinical practice, various autoimmune toxicities have been described. Antibodies targeting the receptor:ligand pairing of programmed death receptor-1 (PD-1) and its cognate ligand programmed death-ligand 1 (PD-L1) in rare reports have been associated with autoimmune diabetes mellitus. We report 2 cases of rapid-onset, insulin-dependent, type 1 diabetes mellitus in the setting of administration of nivolumab, a fully human monoclonal antibody to PD-1, and atezolizumab, a humanized monoclonal antibody to PD-L1. This appears to be the first report of autoimmune diabetes mellitus associated with atezolizumab. In addition, we provide a brief review of similar cases reported in the literature and a discussion of potential mechanisms for this phenomenon and propose a diagnostic and treatment algorithm.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Associated Type 1 Diabetes Mellitus: Case Series, Review of the Literature, and Optimal Management

et al. 2017

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“…More than cases of type 1 acute diabetes, most of them diagnosed in patients treated for a melanoma, have been reported so far in the literature, under anti-PD1, 1 under anti-CTLA4 and anti-PD1 combination and 3 under anti-PDL1 [7][8][9]11,[17][18][19][20][21][24][25][26][27][28][29][30]. (Table 4).…”

Section: Discussionmentioning

confidence: 99%

Diabetes and Blood Glucose Disorders Under Anti-PD1

Magis

Gaudy‐Marqueste

Basire

et al. 2018

Journal of Immunotherapy

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Acute type 1 diabetes (AD1) is a rare but definitive immune-related adverse event associated with anti-PD1. Most of the reported cases are close to what has been described as "fulminant type 1 diabetes." We sought to determine whether anti-PD1 could impair glycoregulation and whether occurrence of AD1 could be anticipated by prior glycemic changes. Fasting glycemia collected before, under, and after treatment in melanoma patients treated with anti-PD1 over a period of 36 months were retrospectively analyzed. Glycemic trend analyses were performed using linear regression analysis. In total, 1470 glucose values were monitored in 163 patients treated for a mean duration of 5.96 months. Three patients developed an AD1 (1, 84%). Two other cases were observed in the same period in a still-blinded trial of anti-PD1 versus ipilimumab. All cases of AD1 occurred in patients with a normal pretreatment glycemia, and there was no detectable drift of glycemia before ketoacidosis onset. In 4 of 5 cases of AD1, the HLA subgroups were DRB01* 03 or 04, known to increase type 1 diabetes risk in the general population. In the 28 patients with preexisting type 2 diabetes, there was a slight trend for glycemia increase with anti-PD1 infusions (0.05 mmol/L/infusion P=0.004). In the 132 patients with normal pretreatment glycemia, there was a slight trend for a decrease of glycemia with anti-PD1 infusions (-0.012/mmol/L/infusion P=0.026). These data suggest that the monitoring of glycemia under anti-PD1 cannot help to anticipate AD1, and there is no general tendency to glycemic disorder. HLA genotyping before treatment may help to focus surveillance in patients with the HLA DRB1*03/04 group.

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“…The incidence of immunotherapy‐induced Type 1 diabetes is reported to be ~0.4% ; however, reports suggest that the real‐world incidence may be significantly higher . Cohort studies of islet antibody‐positive people (mainly first‐degree relatives of people with Type 1 diabetes) have found that ~10% with a single positive antibody will progress to Type 1 diabetes .…”

Section: Introductionmentioning

confidence: 99%

Diabetes associated with immune checkpoint inhibition: presentation and management challenges

Galligan

Fourlanos

et al. 2018

Diabet. Med.

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Onset of diabetes occurred within 12 weeks of commencing therapy. Anti- GAD antibodies were present in six people. Retrospective testing of islet antibodies in pre-treatment samples was possible in two people and this revealed anti-GAD seroconversion in the first and high anti-GAD titres pre and post-treatment in the second person. Six people had high risk HLA haplotypes. Clinical and genetic factors are described and compared with previously published cases. This article is protected by copyright. All rights reserved.

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Case of type 1 diabetes associated with less‐dose nivolumab therapy in a melanoma patient

Cited by 43 publications

References 5 publications

Immune Checkpoint Inhibitor-Associated Type 1 Diabetes Mellitus: Case Series, Review of the Literature, and Optimal Management

Immune Checkpoint Inhibitor-Associated Type 1 Diabetes Mellitus: Case Series, Review of the Literature, and Optimal Management

Diabetes and Blood Glucose Disorders Under Anti-PD1

Diabetes associated with immune checkpoint inhibition: presentation and management challenges

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