Category: Adrenal Disorders
Objective : Immune mediated endocrinopathies are well-known adverse effects of anti-programmed death-1 immunotherapy like nivolumab. Endocrinopathies associated with brentuximab vedotin, a CD30 antibody-drug conjugate, have yet to be extensively reported. We describe a patient who developed secondary adrenal insufficiency (AI) only after adding brentuximab vedotin to ongoing nivolumab therapy.
Methods : n/a
Results : n/a
A 67-year-old male with classic Hodgkin’s lymphoma was started on nivolumab in June 2015 with complete response until December 2016 when he was found to have a target lesion in his right supraclavicular region. Micrometastases were treated with brentuximab vedotin with continued nivolumab. The second cycle was complicated by fatigue, exertional dyspnea, insomnia, rash, pruritus, anorexia, myalgias, peripheral neuropathy, and 15 pound weight loss not expected with brentuximab vedotin alone. One day following his fourth cycle, he developed rapid onset fatigue, tachycardia, abdominal pain, and emesis. Brentuximab vedotin was discontinued but he remained on nivolumab for one more cycle. He continued to have decreased appetite, 30 pound weight loss, nausea, fatigue, and cold intolerance.
Baseline 8 AM cortisol level was 1 (8-25 mcg/dL) with ACTH 9 (6-59 pg/mL). Cortisol inadequately rose to 10 mcg/dL after cosyntropin simulation. Total testosterone was 415 (264 – 916 ng/dL) with bioavailable testosterone 71 (95 – 285 ng/dL) and SHBG 102.5 (19.3 - 76.4 nmol/L). LH 19.6 (2-12 mIU/mL) and FSH 15.1 (1.6-9 mIU/mL) were elevated. Prolactin was 25.7 (3.8-18.9 ng/mL). IGF-1 125 (60 - 220 ng/mL) and growth hormone 0.62 (0.05 - 3.00 ng/mL) levels were normal. TSH was 4.9 (0.450 - 4.500 uIU/mL) with free T4 0.6 (0.82 - 1.77 ng/dL) and free T3 468 (222 - 383 pg/dL). MRI of the pituitary gland showed no masses. He was started on hydrocortisone 10 mg qAM and 5 mg qPM, levothyroxine 50 mcg daily, and testosterone gel.
Conclusion : We present a patient who had been on nivolumab, which is known to cause hypophysitis and AI, but did not exhibit symptoms of disease until brentuximab vedotin was added to his regimen. It is unlikely that AI resulted from nivolumab alone since endocrine side effects occur 5-36 weeks after its initiation, and our patient had been stable on nivolumab monotherapy for two years. Little is known about the combined use of nivolumab and brentuximab vedotin but is being evaluated in multiple clinical trials. We propose a possible additive effect or drug interaction of combination therapy resulting in symptomatic secondary AI. The role of empiric steroids with combined nivolumab and brentuximab vedotin has not yet been studied but could prevent adverse outcomes.
Sahar Sherf– Endocrinology Fellow, UCLA
Sarah S. Kim– Assistant Clinical Professor, Division of Endocrinology - Diabetes and Metabolism, UCLA
John Timmerman– Assistant Clinical Professor, Division of Endocrinology - Diabetes and Metabolism, UCLA
Patricia Young– Clinical Instructor, Division of Hematology/Oncology, University of California, Los Angeles
Dr. Sahar Sherf is a second year UCLA-VA clinical endocrinology fellow.
Assistant Clinical Professor, Division of Endocrinology - Diabetes and Metabolism
Dr. Sarah S. Kim received a Bachelor of Science degree in Computer Science and Electrical Engineering with a minor in Biomedical Engineering at the Massachusetts Institute of Technology in Cambridge, Massachusetts. She completed her medical school training at Drexel University College of Medicine in Philadelphia, Pennsylvania where she was inducted into the Alpha Omega Alpha Honor Society. She spent an additional year doing research in therapies for advanced thyroid cancer. She returned back to Los Angeles and completed her residency training in Internal Medicine at UCLA. She stayed at UCLA for her sub-specialty training in Endocrinology. She then joined the faculty at UCLA and practices general endocrinology in Santa Monica. She speaks fluent Korean and medical Spanish.