2074 Background: Some clinicians have reported initial series of severe or fatal adverse drug reactions (ADRs) that affected large hematology-oncology patient numbers and for which pharmaceutical manufacturers subsequently paid large settlements or fines for allegedly failing to inform physicians about such ADRs. Based on their large human costs ( > 1,000 serious illnesses or deaths) and large financial costs ( > $100 million in settlements or fines), we have termed these ADRs as titanic ADRs. At a Senate hearing on one titanic, Vioxx, (a COX-2 inhibitor that was evaluated for colorectal cancer prevention), the clinician reporter was termed a “whistleblower” by a senator although this individual had not filed a formal whistleblower lawsuit. We identified physicians who would fit this characterization of whistleblowers and had published titanic hematology-oncology ADR reports in high impact journals. Methods: Hematology-oncology titanic ADRs were identified by collaborators with two NIH-funded drug safety networks (RADAR and SONAR (1998-2019)). Exclusion criteria included having also filed a whistleblower lawsuit. Qualitative research analyses evaluated content of statements made by whistleblowers to national reporters or at congressional hearings. Results: 18 physicians who reported titanic hematology/oncology-associated ADRs in peer-reviewed literature and discussed their findings in national news media outlets are included. Titanic ADRs included death, nephrogenic systemic fibrosis, coronary artery disease, and venous thromboembolism related to COX-2 inhibitors, heparin, gadolinium dye, thalidomide, lenalidomide, epoetin, and darbepoetin. Related financial settlements ranged from $100 million to $4.85 billion. Whistleblowers were from the United States, Denmark, and Germany. Primary motivations were public health and medical awareness. Whistleblowers reported having gone through lawsuits and having had executives request that the whistleblowers’ university terminate employment. One whistleblower was quoted saying “I believe that the lawsuit is an attempt to silence me.” Conclusions: Clinician whistleblowers of titanic hematology-oncology ADRs experienced reputational, financial, and personal threats. Motivations for reporting titanic ADRs were mainly public health and medical awareness focused. This differs from our previous study on clinicians publishing on non-titanic ADRs, where the primary motivation was scientific curiosity.