Lenalidomide-Induced Electrolyte Abnormalities: An Unconfounded Case of Acute Severe Refractory Hypocalcemia

Introduction: Lenalidomide is an immunomodulator often used to treat multiple myeloma (MM) and MDS. While it has various hematologic and constitutional side effects, serious electrolyte disturbances like hypocalcemia are rarely reported and are confounded by bisphosphonates or chemotherapy. We present a case of acute, severe, refractory hypocalcemia in a patient receiving lenalidomide without other causative medications. Case Description: A 49-year-old man presented to the ED with severe hand and foot weakness and perioral numbness. 10 months prior, he was diagnosed with IgA Lambda MM and received daratumumab, bortezomib, lenalidomide, and dexamethasone induction with zoledronic acid x2 before autologous stem cell transplant 4 months later. 11 days before admission, he started daratumumab and lenalidomide maintenance. On arrival, he had Chvostek’s and Trousseau’s signs. Labs confirmed severe depletion of calcium (6.2mg/dl), ionized calcium (0.8mmol/L), magnesium (<0.6mg/dl), potassium (2.9mg/dl), and vitamin D (17ng/ml). He had an appropriately elevated PTH (344pg/ml) and his MM was in remission without new lytic lesions. Lenalidomide was held. Several pushes of calcium gluconate, IV KCl and IV MgOx improved his symptoms but not his labs. He started high dose calcium carbonate and calcitriol, but still required 48 hrs of 10% calcium infusion, >1.2 g/day of MgOx, and >100mEq/day KCl to normalize his electrolytes. 2 months later, lenalidomide was restarted and despite his high dose supplements, his calcium dropped (8mg/dl) with his vitamin D (16ng/ml) and magnesium (1.3mg/dl). He continued calcium carbonate 3g TID, started ergocalciferol 50,000 units weekly, and his calcitriol and MgOx were increased to 2mcg daily and 1200mg daily. 6 months later, he is asymptomatic with stable labs. Discussion: To our knowledge, this is the first case of lenalidomide without recent bisphosphonates or chemotherapy to cause severe refractory hypocalcemia within days of initiation. This case underscores the importance of proactive electrolyte and vitamin D monitoring in patients receiving lenalidomide as hypocalcemia can occur acutely even without the usual culprit medications. While the benefits lenalidomide in controlling MM and preventing skeletal complications are well established, their metabolic side effects can be serious and life-threatening if not promptly identified and managed.