SAT258 Successful Treatment Of Adult T-cell Leukemia-lymphoma Induced Hypercalcemia With Denosumab
Authors: Yuksel Simge , Lopez Fanas Raul , Schwartz Deborah , Tabatabaie Vafa , Sachdev Saachi 
Published: October 2023

Abstract
Disclosure: S. Yuksel: None. R. Lopez Fanas: None. D. Schwartz: None. V. Tabatabaie: None. S. Sachdev: None.
Introduction: Adult T-cell leukemia/lymphoma (ATLL) is a rare, aggressive lymphoproliferative disorder associated with human T-cell leukemia virus type 1 (HTLV-1), often presenting with severe refractory hypercalcemia. Here, we present a rare case of bisphosphonate-resistant ATLL-associated hypercalcemia successfully treated with denosumab (Dmab). Clinical Case: A 47-year-old woman from Jamaica presented with pruritic rash of left forearm and bilateral lower extremity (LE) pain for 6 weeks. Laboratory evaluation noted serum Ca of 16.2 mg/dL (n 9-11), PTH 12.5 pg/mL (n 16-65), PTHrP 24 pg/mL (n 11-20) and 25(OH)D 16 ng/mL (n 30-60). 1,25(OH)2D level was normal. Cr was 1.5 mg/dL (n 0.7-1.2). X-rays demonstrated punctate lytic lesions throughout LEs. The patient received IV fluids, calcitonin, pamidronate 60 mg IV, and ergocalciferol 50,000 IU. Corrected Ca (cCa) improved to 9.3 mg/dL. However, hypercalcemia recurred after 2 days. HTLV-1 serology was positive. Flow cytometry and bone marrow biopsy were consistent with ATLL. When Ca rose to 14.3 mg/dL, Dmab 60 mg SC was administered. Within 1 week, she developed asymptomatic hypocalcemia with cCa of 7.1 mg/dL requiring oral calcium citrate and calcitriol. Stable normocalcemia was achieved after 10 days. Hospital course was complicated by pathologic right wrist fracture. Palliative radiation to LE was initiated. She was discharged on calcium citrate 2850 mg TID, calcitriol 0.25 mcg BID and ergocalciferol 50,000 IU weekly. The patient was treated with 6 cycles of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab, as well as intrathecal methotrexate for CNS prophylaxis. She received 120 mg of Dmab 6 months after the first dose. Ca remained stable. Conclusion: ATLL-associated hypercalcemia is mediated by increased secretion of PTHrP, and RANK ligand and proinflammatory cytokines that promote RANK expression. Dmab is an effective treatment for ATLL-associated hypercalcemia as it specifically targets RANK ligand. A dose of 120 mg Dmab is recommended for patients with bisphosphonate-resistant hypercalcemia of malignancy and GFR greater than 30 mL/min. In another published case report on the use of Dmab in ATLL-associated hypercalcemia, treatment with Dmab 120 mg SC resulted in protracted hypocalcemia lasting 5 months despite calcium carbonate and Vitamin D supplements (1). Our patient had a significantly shorter hypocalcemia course likely due to reduced Dmab dose and more aggressive proactive treatment with ergocalciferol, calcium citrate and calcitriol. This case supports the successful use of Dmab in bisphosphonate-resistant ATLL-associated hypercalcemia. Protracted Dmab-induced hypocalcemia may be mitigated by Dmab dose reduction even in the presence of normal GFR and early aggressive treatment with calcium citrate and calcitriol. Reference: (1) Japp et al. AACE Clin Case Rep.2019;5:e210-213
Presentation: Saturday, June 17, 2023