8690 Severe Hypocalcemia Following Treatment with Venetoclax for AML

Abstract Disclosure: K. Ruddiman: None. C. Price: None. Background: Venetoclax is a chemotherapeutic agent which has known side effects of tumor lysis syndrome, but few reports of isolated hypocalcemia. Clinical case: A 73 year old male with medical history pertinent for myeloproliferative and myelodysplastic disease was admitted for evaluation of failure to thrive. Workup revealed progression to acute myeloid leukemia. Following treatment with decitabine 34mg/day for 5 doses and initiation of venetoclax 100mg daily, he developed progressive, severe, symptomatic hypocalcemia with positive Trousseau and Chvostek sign. The patient was normocalcemic prior to admission with serum calcium ranging between 8.6-9.7mg/dL. Corrected calcium at admission was 8.8mg/dL. Serum calcium decreased steadily following venetoclax, requiring repletion with 3 doses of calcium chloride and gluconate 1gm IV and initiation of oral calcium carbonate 1900mg TID. At its nadir, corrected calcium was 6.1mg/dL on day 19 of treatment with venetoclax despite oral and IV repletion. Further workup showed undetectable 25 hydroxy vitamin D, PTH 62pg/mL, normal range uric acid, low phosphorus (lowest 2.2mg/dL), mild hypokalemia (lowest 3.2mg/dL), and mild hypomagnesemia of 1.8mg/dL. GFR was >90mL/min. Hypocalcemia improved after 3 infusions of calcium gluconate 10gm IV in 1 L normal saline to 7.2mg/dL. Oral repletion with calcium carbonate was transitioned to calcium citrate due to concomitant PPI use. PO calcium citrate titrated to 2850 mg TID to target corrected calcium 7.5 - 8.5 and limit further need for diuresis following calcium gluconate infusions. Ergocalciferol 50,000 IU was given thrice weekly in addition to daily cholecalciferol 5,000 IU with improvement in 25 hydroxy vitamin D to 17ng/mL. This patient was suspected to have multifactorial etiology for hypocalcemia, secondary to undetectable 25 hydroxy vitamin D as well as diuresis with furosemide during the admission, but the most strongly attributed factor was initiation of venetoclax prior to development of progressive hypocalcemia. FDA prescribing information reports hypocalcemia as a side effect of venetoclax when used in treatment for CML, but in phase 2 and 3 studies of venetoclax used alone and in combination with low dose cytarabine to treat AML, no significant episodes of hypocalcemia were reported. Tumor lysis syndrome (TLS) is a known adverse effect of venetoclax in which hypocalcemia is an expected feature, however, this patient did not have laboratory to support this diagnosis. His other electrolyte deficiencies were mild and transient. Conclusion: While electrolyte abnormalities associated with TLS are an expected side effect of venetoclax, isolated severe hypocalcemia is a rarely reported side effect. Calcium should be closely monitored during treatment. Presentation: 6/1/2024