SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Carfilzomib is a second generation proteasome inhibitor approved for use in relapsed or refractory multiple myeloma. Pooled safety data from Phase 2 and Phase 3 clinical trials showed 3.8-6.4% incidence of cardiac failure (monotherapy and combination therapy respectively). Review of the ASPIRE trial reveals that 3.8% had cardiac toxicity vs 1.8% in the control group, but there was no increase in cardiovascular death. A recent systematic review and meta-analysis showed overall 8.6% rate of cardiotoxicity in patients treated with carfilzomib which is significantly greater than other proteasome inhibitors. CASE PRESENTATION: The patient is a 53-year-old male with past medical history of hypertension, gastroesophageal reflux disease, and refractory multiple myeloma which was first diagnosed in May 2017. He presented to clinic for routine visit and was noted to have hypercalcemia and acute kidney injury; he was sent for hospital admission. During the admission interview he reported that he had been feeling rather poorly since initiation of his current chemotherapy regimen with progressive chest tightness and severe dyspnea on exertion along with orthopnea, paroxysmal nocturnal dyspnea and peripheral edema. His pre-treatment echocardiogram had been normal. After admission, he had an echocardiogram which showed normal LVEF, dilated RV with severely reduced systolic function, PASP >55mmHg. A VQ scan was negative. A right heart catheterization showed PA pressure 61/34, wedge 23, pulmonary vascular resistance 480dyn-sec/cm5. DISCUSSION: This patient presented with right heart failure and pulmonary hypertension shortly after starting chemotherapy including carfilzomib. Though cardiac toxicity of carfilzomib is well described, early reports primarily consisted of left heart failure. Basic science literature dating back to 2006 showed that proteasome inhibition could modulate eNOS function; more recent literature suggests that carfilzomib specifically increased resting vasogenic tone in arterial samples. His response to standard treatment for Group I pulmonary hypertension also supports the mechanism being related to endothelial dysfunction. There is no way to prove that carfilzomib was the culprit agent; however, the timeline is highly suggestive and increasing literature confirms significant cardiotoxicity of carfilzomib. CONCLUSIONS: Based on the data above, the patient’s cardiac illness was consistent with mixed presentation of chronic heart failure with preserved ejection fraction with superimposed acute pulmonary hypertension. In addition to diuresis, he was started on tadalafil which was well tolerated. These therapies increased exercise tolerance, resolved volume overload and reduced NT pro BNP levels. Reference #1: Shah, C, et al. (2018). Cardiotoxicity associated with carflizomib: Systematic review and meta analysis . Leukemia and Lymphoma, 10. Reference #2: Wei, Q., & Xia, Y. (2006). Proteasome inhibition down-regulates endothelial nitric-oxide synthase phosphorylation and function. Journal of Biological Chemistry , 281(31), 21652–21659. Reference #3: Perel G, Bliss J, Thomas CM. 2016. Carfilzomib (Kyprolis): A Novel Proteasome Inhibitor for Relapsed And/or Refractory Multiple Myeloma.Pharmacy and Therapeutics 41:303–307. DISCLOSURES: no disclosure on file for MaryEllen Antkowiak; No relevant relationships by Julia Powelson, source=Web Response No relevant relationships by Hibba tul Rehman, source=Web Response