Anti–PD-1 Therapy–Associated Type 1 Diabetes in a Pediatric Patient With Relapsed Classical Hodgkin Lymphoma

Abstract

Immune checkpoint inhibitors (ICIs) perturb T-cell regulatory pathways to enhance antitumor immunity. However, an increase reporting of ICI-associated diabetes is observed in adults. To our knowledge, no cases have been reported in the pediatric population. RESEARCH DESIGN AND METHODS We describe a pediatric case of ICI-associated type 1 diabetes in a 12-year-old Hispanic boy with Hodgkin lymphoma. The patient had a history of autologous hematopoietic stem cell transplantation and was treated with pembrolizumab after disease progression. RESULTS The patient was admitted for diabetic ketoacidosis after five cycles of pembrolizumab. The patient was discharged with daily insulin injections and has continued on exogenous insulin ever since. CONCLUSIONS The expanded ICI use may lead to more cases in pediatric patients as has been observed in adults. Considering the acute manifestation of diabetes and the added burden of lifelong insulin therapy, in particular for pediatric patients and their families, monitoring and education of ICI-associated diabetes in children is needed. Insulin-dependent diabetes associated with immune checkpoint inhibitors (ICIs) is a rare phenomenon but of high clinical significance due to its presentation as potentially life-threatening diabetic ketoacidosis (DKA). In the setting of advanced malignancies, ICI-associated diabetes may seem peripheral, but its chronicity, complications, and daily glucose monitoring and insulin injections drastically alter patients' quality of life and complicate cancer treatment. Moreover, the unprecedented level of interest in immunotherapy research will lead to more widespread use of ICIs and a subsequent increase in diabetes, as evidenced by recent data (1-3). One study reported 283 new cases during a 4-year period, with more than half reported in 2017 (1). The primary cancer types were melanoma (43%), lung (32%), and renal (10%), indicative of early ICI approvals in these tumors. While the nature of ICI-associated diabetes is better defined for melanoma, other malignancies, such as lymphoma, are rarely reported, making it difficult to assess patient characteristics in various types of cancer that are approved for ICI use, especially for hematologic malignancies.

Immune‐checkpoint inhibitor‐associated diabetes compared to other diabetes types ‐ A prospective, matched control study

“…In the unmatched cohort, the older age at diagnosis of CPI-DM and the subgroup of patients with medication-induced diabetes compared with T1DM has been reported before 18 and is not surprising, because cancer occurs more frequently with increasing age 19 and the risk for corticoid-induced diabetes typically increases with a longer period of medical treatment. 20 In our cohort, we had approximately equal numbers of men and women with CPI-DM.…”

Coexistence of Immune Checkpoint Inhibitor-Induced Autoimmune Diabetes and Pancreatitis

“…The median age of onset of ICI-induced autoimmune diabetes was 61 years. The onset age of diabetes probably reflects the age of development of malignancies and age at ICI treatment, although it is worth noting that ICI-induced autoimmune diabetes has been reported in a 12-year-old patient with relapsed classical Hodgkin lymphoma ( 20 ).…”

Diabetes mellitus Typ 1 – Update

“…Entsprechend der onkologischen Grunderkrankung liegt das mittlere Alter der betroffenen Patienten über 50 Jahren. Diese Diabetesform kann aber auch bei Kindern auftreten, wie es für ein 12-jähriges Mädchen nach Therapie eines Hodgkin-Lymphoms beschrieben wurde [ 24 ].…”