Daratumumab is the first anti CD 38 monoclonal antibody approved by FDA for management of Multiple Myeloma proven refractory to at least two prior lines of therapy including Proteasome inhibitor or Immunomodulatory agent or those double refractory to a Proteasome inhibitor and an Immunomodulatory agent. The most common adverse effects include Pneumonia, Upper respiratory tract infection, cough and breathlessness along with multilineage cytopenias. A 71-year-old male patient, a known case of hypertension, with past history of pulmonary tuberculosis with family history of bronchial asthma developed breathlessness while receiving the first cycle of intravenous daratumumab. He was diagnosed with Multiple myeloma (Salmon Durie stage iii a) following which he was started on Thalidomide plus dexamethasone which was continued for 2 years. He subsequently underwent an allogeneic stem cell transplantation. He was started on Lenalidomide followed by monthly Bortezomib (12 cycles), Cyclophosphamide and Danazol. He had also received multiple component transfusion for cytopenias since the past three years. He was started on anti-CD 38 monoclonal antibody Daratumumab infusion (800 mg over 4 hours on two consecutive days) following which he developed breathlessness, acute in onset, not associated with any postural variation or noisy breathing and desaturation on Room air. He was prescribed Inj Hydrocortisone and Inj Pheniramine maleate after which he reported symptomatic improvement. There was no recurrence of the symptom during the second cycle of Daratumumab which was given over 6 hours. Discussion The adverse event was classified as possible causality by Naranjo’s algorithm and WHO-UMC causality assessment category. Methods to ameliorate this adverse effect such as prolonging the duration of infusion, use of pre-medication, screening of patients for Bronchial Asthma by Spirometry and formulation of exclusion criteria for the those with underlying severe Obstructive Lung Disease need to be discussed further. The mechanism of Bronchospasm underlying anti CD 38 directed treatment needs to be elucidated further.