Introduction: Immune check point inhibitors (ICI)are monoclonal antibodies that block inhibitory receptors such as CTLA-4 and PDL 1, resulting in the restoring of the immune system to target cancer cells. Rarely, they can be associated with the triad of myositis, myasthenia gravis, and myocarditis or “overlap” syndrome.
Description: 65-year-old male with bladder cancer, left upper tract urothelial cancer underwent radical nephroureterectomy and was given one dose of adjuvant Pembrolizumab. He presented with proximal muscle weakness, dizziness, dysphagia and complete heart block. He underwent placement of a transvenous pacemaker. His initial Echo was normal with EF of 50-55%. Triple M overlap syndrome was high on the differential, and he was initiated on pulse dose steroids with methylprednisolone 1 gm and PLEX for three days. On Day 5 of his hospitalization, the patient developed refractory ventricular tachycardia with ventricular fibrillation arrest. His repeat TTE showed severely depressed EF of < 15% and dilated RV with severely decreased function. Cardiology and oncology recommended to start second line immunosuppression with Ruoxolitinib 15mg BID and Abatacept 20mg/kg q5 days with bridge on ECMO.Patient was supported on ECMO for 7 days while simultaneously receiving steroids, Ruoxolitinib and Abatacept showing improvement in EF to 30-35%. Patient was eventually decannulated from ECMO but required trach for weakness. On hospital day 26, patient had acute respiratory decompensation and eventual cardiac arrest from possible tension pneumothorax. After discussions with family, he transitioned to palliative care.
Discussion: ICI related side effects occur in a relatively low number of patients; with myocarditis having the highest mortality of 25-50%. Triple M overlap syndrome is even more rare with the mortality rising up to 60%. Though steroids remain first line treatment, patients with triple M syndrome are refractory to steroids and will need second line immunosuppression. In our case, these treatments were used in conjunction with ECMO support to optimize cardiac recovery. While the appropriate dosing and duration of these treatments requires additional studies, our case report shows the promising outcomes for this complication with a very high mortality.
