Vaccination induced cytokine storm; IgA-Kappa MM; Severe-symptomatic hypercalcemia; Flu-like symptoms; This literature case was received on 04-Jan-2021, concerning a 65-year-old female patient.  The patient's concurrent conditions included multiple myeloma (MM). The patient's concomitant medications were not reported.  On an unspecified date, the patient was vaccinated with influenza virus vaccine polyvalent (brand not specified; anatomical location, dose, route of administration and indication: not reported). The batch number was not reported.  On an unspecified date, 5 days after receiving influenza virus vaccine polyvalent, the patient presented with subjective myalgias lasting two days. Vital signs were stable, complete blood count (CBC) and basic metabolic panel (BMP) were unremarkable and serum calcium was 10.8 mg/dl. The patient was discharged on supportive therapy.  On an unspecified date, the day later, the patient presented with persistent flu-like symptoms. Labs revealed serum calcium being above 22 mg/dl; normal renal function, total protein, albumin, angiotensin converting enzyme (ACE) levels; clear urine analysis (UA) with no albuminuria; low parathyroid hormone (PTH) and 1, 25-(OH)2-Vitamin D3 levels; elevated parathyroid hormone-related protein (PTHrP) and viscosity levels. 24-hour urine collection revealed proteinuria (550 mg). Peripheral blood smear revealed rouleaux formation. Computerized tomography (CT) scans of the chest, abdomen and pelvis revealed no obvious malignancy. Quantitative immunoglobulins (Ig) revealed elevated IgA (2415 mg/dl), and concurrent suppression of IgG and IgM levels. Quantitative serum light chain measurement revealed normal levels of kappa and lambda, with an elevated Kappa: Lambda ratio of 2:1. Serum protein electrophoresis (SPEP), urine protein electro-phoresis (UPEP) and serum immunofixation revealed IgA-Kappa MM. The patient developed severe-symptomatic hypercalcemia, she was treated with aggressive intravenous crystalloids, loop diuretics, calcitonin, Pamidronate (pamidronate disodium), and hemodialysis. The patient's calcium subsequently normalized to 10.1 mg/dl. Bone-marrow biopsy revealed intracytoplasmic kappa-restricted monoclonal plasma cells that occupied 40% of the marrow. Bone survey was negative for lytic lesions. The patient was started on bortezomib, lenalidomide, dexamethasone and monthly zoledronic acid, and she has not attained remission from myeloma yet.  On an unknown date, the patient recovered from the event 'hypercalcemia'.  At the time of initial report, the patient had not recovered from 'multiple myeloma'.  The outcome of all the rest events was not reported.   The reporters assessed the event of 'cytokine storm' as related to the influenza virus vaccine polyvalent. It was theorized that the inactivated influenza vaccine given prior to presentation unmasked an atypical presentation of MM. This may be attributed to a vaccination induced cytokine storm, especially IL-6 mediated that may be the key in the pathophysiology of hypercalcemia related to MM. The reporter did not provide a causality assessment for other events.  The events of 'cytokine storm' and 'multiple myeloma' were considered to be medically significant by a Physician within Seqirus's Pharmacovigilance and Risk Management Department.    Company comment: A 65-year-old female patient experienced cytokine storm, plasma cell myeloma, hypercalcemia and influenza like illness. Symptoms of the reported events started emerging one day after administration of influenza virus vaccine polyvalent. Very detail laboratory and diagnostic findings were provided in the report. Causality is assessed as possibly related for influenza like illness and for cytokine storm due to biological plausibility and presented information and unrelated for plasma cell myeloma due to biological and temporal implausibility. Hypercalcemia is more likely related to myeloma however the reporter's rationale points to vaccine as well, therefore assessed as unlikely related. (''unlikely related'' defaults to ''related'' in the safety database for reporting purposes); Reporter's Comments: It was theorized that the inactivated influenza vaccine given prior to presentation unmasked an atypical presentation of MM. This may be attributed to a vaccination induced cytokine storm, especially IL-6 mediated, that may be the key in the pathophysiology of hypercalcemia related to MM.; Sender's Comments: A 65-year-old female patient experienced cytokine storm, plasma cell myeloma, hypercalcemia and influenza like illness. Symptoms of the reported events started emerging one day after administration of influenza virus vaccine polyvalent. Very detail laboratory and diagnostic findings were provided in the report. Causality is assessed as possibly related for influenza like illness and for cytokine storm due to biological plausibility and presented information and unrelated for plasma cell myeloma due to biological and temporal implausibility. Hypercalcemia is more likely related to myeloma however the reporter's rationale points to vaccine as well, therefore assessed as unlikely related. (''unlikely related'' defaults to ''related'' in the safety database for reporting purposes)