This article brings forth the hypothesis that elotuzumab can cause pneumonitis, and discontinuation of elotuzumab along with high-dose corticosteroids helps reverse the pneumonitis. strong class=”kwd-title” Keywords: interstitial pneumonitis, elotuzumab, multiple myeloma Introduction Humanized IgG1 monoclonal antibody elotuzumab (HuLuc63) that targets signalling lymphocytic activation molecule F7 (SLAMF7)?[1-3]. IgG1 monoclonal antibody elotuzumab (HuLuc63) that targets signalling lymphocytic activation molecule F7 (SLAMF7)?[1-3]. Multiple myeloma cell death is caused by it through direct activation of natural killer cells targeted at neoplastic plasma cells through Fc receptors (CD16), SLAMF7 pathway and by tagging them for recognition of ADCC (antibody-dependent cellular toxicity). With little to no expression of SLAMF7 protein in normal tissues, elotuzumab selectively kills multiple myeloma cells with minimal off-target effects?[4]. In November 2015, food and drug administration (FDA) approved the combination therapy of elotuzumab with lenalidomide and dexamethasone (Elo-Ld) based on ELOQUENT-2 trial on adult patients with one prior therapy?[5]. Elotuzumab combined with pomalidomide and dexamethasone (Elo-Pd) has been approved for use in multiple myeloma patients having received two previous therapies, including lenalidomide and PI (protease inhibitor) in Apioside 2018 after ELOQUENT-3 trial?[6]. There are numerous side effects associated with elotuzumab combination therapy, including lymphopenia, fatigue, diarrhoea, pyrexia, constipation, cough, peripheral neuropathy and nasopharyngitis?[5]. Pulmonary toxicity associated with elotuzumab (combined with lenalidomide/pomalidomide and dexamethasone) was barely described in Phase 1-3 clinical trials?[5-7]. Only one case report of elotuzumab induced interstitial lung disease exists?[8], with a few cases reports on lenalidomide and pomalidomide induced interstitial lung disease?[9-14]. This article covers two cases of acute hypoxic respiratory failure upon administration of elotuzumab, and both treated successfully with corticosteroids. Case Apioside presentation Case 1? A 50-year-old male having a history of multiple myeloma (IgG kappa), on weekly elotuzumab infusion for last five weeks (last infusion four days before admission) along Apioside with lenalidomide and dexamethasone presented to emergency with four-day symptoms of shortness of breath, fatigue and malaise. He also reported dry cough. He denied having fever, chills, night sweats, chest pain, abdominal pain, nausea, vomiting, diarrhoea, urinary changes and lower extremity swelling. The patient was diagnosed with pulmonary embolism a month back. Compliance of the patient with therapeutic dose enoxaparin was documented. On initial evaluation, the patient was hypoxic requiring 2-3-litres oxygen, later increased to 15 litres high flow nasal cannula, and eventually stabilized on bilevel positive airway pressure (BiPAP). On physical examination, he had a temperature of 101.3 F, and faint crackles (heard bilaterally at bases) on chest examination. Apioside Cardiovascular, gastrointestinal, and neurological examinations were normal. Laboratory tests revealed thrombocytopenia (platelets (PLT) 16 x 109/L) and anaemia (Hb 7.8 g/dl) consistent with initial baseline values, acute kidney injury (creatinine 1.28 mg/dl), mild pro-BNP elevation (394 pg/ml) with insignificant electrocardiogram abnormality. Viral respiratory pathogens polymerase chain reaction (PCR), COVID-19 PCR, legionella, and streptococcal urine antigens were negative. CT Chest with pulmonary embolism protocol demonstrated the decreased size of previously seen filling defect within right lower lobe segmental artery but new bilateral diffuse ground-glass opacities (Figure?1). Elotuzumab induced pneumonitis, sepsis, pulmonary edema, and multifocal pneumonia were taken as a differential diagnosis. The patient was admitted, blood and urine cultures were sent and started on vancomycin along with meropenem. Normal systolic function (ejection fraction 50%), normal wall motion with no right to left shunt were observed on echocardiogram with bubble study. Continued administration of antibiotics with an observation period of one to two days was suggested by the haematologist along with administration of corticosteroids for possible elotuzumab induced pneumonitis if the patient did not improve under the antibiotics. Open in a separate window Figure 1 Axial contrast-enhanced CT chest (lung window) showing bilateral diffuse ground-glass opacities. The patient continued to have shortness of breath requiring 10-15-litres oxygen on high flow nasal cannula and intermittent BIPAP over the next 24 hours. He was started on methylprednisolone (125 mg) every six hours after consultation with the haematologist. This brought down the oxygen requirement to 6 litres/min the next day, but the malaise persisted. Antibiotics were stopped since the urine and blood cultures were negative. Significant improvement was observed on the fourth day of F2r intravenous methylprednisolone as the patient ambulated comfortably. He was not requiring any oxygen, was ambulating without difficulty. The patient was discharged with.