Abstract Introduction Multicentric Castleman’s disease (MCD) is a rare lymphoproliferative disorder that has been previously associated with pulmonary arterial hypertension (PAH). MCD results from polyclonal plasma cell dyscrasia leading to upregulation of serum IL-6 causing systemic lymphadenopathy, hepatosplenomegaly, constitutional symptoms, and, in some cases, severe PAH. Interestingly, PAH has shared molecular mechanisms to development of MCD through BMP downregulation and IL-6 and VEGF upregulation. Prior clinical trial TRANSFORM-UK, treated PAH patients with tocilizumab, an IL-6 receptor antagonist, but did not find a mortality benefit. Treatment with IL-6 monoclonal antibody siltuximab is now standard of care for treatment of MCD regardless of PAH status. We present a case of a patient with MCD with mixed pre- and post-capillary pulmonary hypertension who is treated with siltuximab. Case Our patient is a 60-year-old male with mixed pre- and post-capillary pulmonary hypertension with history of MCD, heart failure with reduced ejection fraction (LVEF 38%), and chronic kidney disease. Prior to pulmonary consultation, patient presented with constitutional symptoms, diffuse lymphadenopathy, and acute renal failure requiring renal replacement therapy. Work-up consisted of PET-CT with extensive FDG-avid lymphadenopathy and renal and lymph node biopsies consistent with MCD diagnosis. Labs were notable for negative serum HHV-8 and elevation of IL-6 (180), IL-2 receptor-alpha (11,299), and VEGF (201). Hematology/oncology determined that patient met criteria for idiopathic MCD (iMCD) given HHV-8 negativity, 2 major criteria, and 6 minor criteria as determined by the American Society of Hematology. Right heart catheterization demonstrated RAP 13 mmHg, mPAP 48 mmHg, PCWP 16 mmHg, Fick CO 4.2 L/min, PVR 7.6 woods units. PFTs demonstrating no airflow restriction, normal lung volumes, and adjusted DLCO 12.5 (50%). LFTs, HIV, rheumatologic markers negative, and V/Q scan were all negative. Patient currently treated with siltuximab every 3 weeks. Serum inflammatory markers are now downtrending. Repeat TTE after months of treatment demonstrate recovery of right ventricular function and normal TAPSE. Discussion Patient with WHO group I/II pulmonary hypertension secondary to iMCD and heart failure is receiving siltuximab to target reduction of IL-6 inflammation. Siltuximab treatment has improved at minimum right ventricular function. His functional improvement is encouraging given shared upregulation of IL-6 cytokines in PAH and iMCD. We plan to repeat right heart catheterization to fully quantify impact of siltuximab treatment on pulmonary hypertension. Siltuximab may be useful as a target for a subset of PAH patients in the future. This abstract is funded by: None
Arai et al. (Fri,) studied this question.