Background: Nivolumab showed promising results in phase II clinical trials for advanced MM patients with good performance status (PS). Limited data exists for poor PS patients treated outside of clinical trial. We report the efficacy and safety in patients enrolled in a Nivolumab expanded-access program (EAP). Methods: 27 advanced MM patients were enrolled in EAP and treated from 12/2015 - 12/2017 at Mesothelioma Treatment Center at Baylor College of Medicine. Nivolumab 3 mg/kg was administered every 2 weeks until disease progression. Blinded radiologist assessed responses using RECIST 1.1 criteria. Baseline tumor volumes (BTV) were measured. PD-L-1 expression on tumor samples was quantified by PD-L1 IHC 28-8 pharmDx assay. Results: 25 patients were evaluable (2 patients expired before evaluation for response). Median age was 67 years (range 38-89). 72% were male, 56% had PS ≥ 2; epithelioid/ biphasic histologies: 76%/24%. Median follow up time was 6 months (range 2-23). 72% received Nivolumab as second line or later therapy. Median progression free survival was 5 months. Response rate was 24% (3 CR, 3 PR); 9 stable disease (SD), disease control rate (DCR) was 60% (CR+PR+SD). Median duration of response 6 months (range 2-24). For patients with PS ≥ 2, DCR was 50%. For patients treated as first line, DCR was 42%. 20 patients had PDL-1 expression evaluated; DCR was 55% in patients (45%) with PDL1 < 1%, and 63% in those with PD L 1 > 1%. Median BTV was 251 cm³, DCR was 50% for patients with BTV > median and 75% for patients with BTV < median. At 6 months, 52% of patients were alive. Grade 1/2 adverse events (AE) include skin rash (1), body aches/arthritis (2) and enteritis/diarrhea (2). No grade 3/4 AE or treatment related death occurred. Conclusions: Nivolumab is effective and safe for MM patients with poor PS. Durable responses were achieved in a subset of patients. Our limited data showed responses regardless of tumor PD-L1 expression. Smaller BTV may predict response but validation of this observation is warranted.