We performed a pooled analysis of published literature and institutional experience to understand the predictive value of programmed death receptor-ligand 1 expression on tumor response after checkpoint immunotherapy for pulmonary sarcomatoid carcinoma, a rare subtype of non-small cell lung cancer. As the level of programmed death receptor-ligand 1 expression increased, both tumor response and progression-free survival also significantly increased. Background: Pulmonary sarcomatoid carcinoma (PSC) or pleomorphic carcinoma is a rare subtype of non-small cell lung cancer. Some reports have suggested the efficacy of checkpoint inhibitor immunotherapy for PSC. However, owing to the small number of patients in each report, it remains unclear whether programmed death receptor-ligand 1 (PD-L1) expression is predictive of tumor response or survival. Patients and Methods: The English literature was systematically searched for articles published from 2015 to 2019 and reported on tumor response or progression-free survival (PFS) after immunotherapy for advanced PSC. In addition, our institutional electronic medical records were searched for eligible cases to be included. Pooled analyses were performed. Results: Analyses included 90 patients. Best tumor response was partial or complete response in 54.5%, stable disease 15.9%, and progressive disease in 29.6%. The median PFS was 7.0 months. Among 66 patients with reported PD-L1 expression, the level was <1% in 7 patients (10.6%), 1%-49% in 10 patients (15.2%), and 50% in 49 patients (74.2%). A positive relationship between PD-L1 level and tumor response was observed. Among 47 patients with a PD-L1 of 50%, 33 patients (70.2%) achieved response, compared with 5 of 10 patients (50%) with a PD-L1 of 1%-49% and 2 of 7 patients (28.6%) with a PD-L1 of <1% (P ¼ .026). PFS was superior among patients with a PD-L1 of 1% compared with those with a PD-L1 of <1% (14.4 months vs. 2.7 months respectively; P ¼ .04). Conclusions: Among patients with advanced PSC, PD-L1 expression is significantly associated with increased tumor responses and improved PFS after checkpoint inhibitor immunotherapy.

ObjectiveImmune checkpoint blockade therapy (ICBT) increases the anti-tumoural function of the immune system, but it can also induce immune-related adverse events (irAEs). Our aim was to assess the irAEs due to ICBT in patients from a single centre of Northern Spain. MethodsWe set up an observational study of patients treated in monotherapy with ICBT targeted against cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1) or its ligand (PD-L1) for solid organ tumours. All patients were followed up in a single University Hospital from March 2015 to September 2018. ResultsWe studied 102 patients (63 men/39 women); mean age 60.6±9.7 years, with lung (n=63), melanoma (n=21), kidney (n=11), gastric (n=3), colon (n=3) or bladder (n=1) cancer. Only 7 patients had a previous diagnosis of an immune-mediated disease, specifically: psoriasis (n=2), psoriatic arthritis (n=1), systemic lupus erythematosus (n=1), spondyloarthitis (n=1), rheumatoid arthritis (n=1) and cutaneous lupus (n=1). One of the following ICBT was administered: nivolumab (n=52), pembrolizumab (n=35), atezolizumab (n=10) and ipilimumab (n=5). After a mean follow-up time of 14.4±7.7 months since ICBT onset, 87 (85.3%) patients had experienced irAEs, mostly gastrointestinal, thyroid and musculskeletal manifestations including inflammatory arthralgia (n= 8), arthritis (n= 6) and myositis (n=2). ICBT was discontinued in 41 patients but it was reintroduced in 30 of them after resolution of the adverse event, with a good tolerance in all cases. Thirty-six (41.4%) of the 87 patients required specific treatment (prednisone, levothyroxine, and thiamazol) for the irAEs. Conclusion irAEs are frequent in patients undergoing ICBT. Almost half of the patients that have irAEs require treatment.Musculoskeletal manifestations are not uncommon.

BackgroundImmune checkpoint blockade therapy (ICBT) has shown remarkable benefit in different cancer types. Blockade of intrinsic down-regulators of immunity increases the activity of the immune system, which can lead to different immune-related adverse events (irAEs). Our aim was to assess the immune-related adverse events in patients who received anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1).ObjectivesOur aim was to assess the incidence, treatment and evolution of irAEs due to ICBT.MethodsWe set up an observational study of patients treated with Nivolumab and Pembrolizumab (anti-PD1), Atezolizumab (anti-PD-L1) and Ipilimumab (antiCTLA-4) for solid organ tumors. All these patients were followed in a single reference University Hospital from March-2015 up to December-2018. The main outcome was to determinate the incidence of irAEs.ResultsWe studied 102 patients (63♂/39♀) with a mean age of 60.6±9.7 with lung(n=63), melanoma (21), kidney (11), gastric (3), bladder (1), and colon cancer (n=3). Only 7 patients had a previous diagnosis of an immune-mediated disease: psoriasis (n=2), psoriatic arthritis (1), systemic lupus erythematosus(1), spondyloarthitis (1), rheumatoid arthritis (1) and skin lupus (1).ICTB was performed as follows: nivolumab (n=52), pembrolizumab (35), atezolizumab (10) and ipilimumab (5).After a median of 5 [2.5-10.5] months since the ICBT onset, we observed 87(85.3%) patients with different irAEs, summarized in TABLE. ICBT discontinuation was required in 39 patients. 36 patients received specific treatment (prednisone, antihistamine, levothyroxine and thiamazol), obtaining a good response in 31 cases (79.5%). ICBT was reintroduced in 28 patients (71.8%) after resolution of the adverse event, with an appropriate tolerance in all cases.Gastrointestinal irAEs were the most frequent (n=39, 41.1%), with severe manifestations in 4.9% of the patients. Among these 39 patients, only 11 of them required specific treatment, with oral prednisone in all cases. The diagnosis of gastrointestinal irAEs was based on the clinical manifestations and the laboratory tests. The cutaneous most frequent irAE was rash (n=7, 6.8%), followed by vitiligo (n=2, 1.9%). 15 patients developed a rheumatological irAE (14 arthralgias/arthritis and 1 aortitis).Patients who developed any type of irAE had a better answer to ICBT (70.1%) than those who did not (20%).ConclusionIn our study, the majority of autoimmune side effects due to ICBT were gastrointestinal, thyroiditis and rheumatological. The develop of any irAE could be an indicator of good response to ICBT.Disclosure of InterestsLara Sánchez Bilbao: None declared, Iñigo González-Mazón: None declared, José Luis Martín-Varillas: None declared, Marina Delgado Ruiz: None declared, Isabel Bernat Piña: None declared, Belén Atienza-Mateo: None declared, D. Prieto-Peña: None declared, Monica Calderón-Goercke: None declared, Almudena García Castaño: None declared, Ricardo Blanco Grant/research support...

BackgroundImmune checkpoint blockade therapy (ICBT) currently is one of the most used therapies against cancer. The activation of the immune system can lead to different immune-related adverse events (irAEs), being the rheumatological side effects among the most common.ObjectivesOur aim was to assess the rheumatological irAEs in patients who received immunotherapy.MethodsWe set up an observational study of patients treated with Nivolumab and Pembrolizumab (anti-PD1), Atezolizumab (anti-PD-L1) and Ipilimumab (antiCTLA-4) for solid organ tumors. All these patients were followed in a single reference University Hospital from March-2015 up to December-2018. The main outcome was to determinate the incidence of rheumatological irAEs.ResultsWe studied 102 patients (63♂/39♀) with a mean age of 60.6±9.7 with different solid organ tumors. Only 7 patients (6.8%) had a previous diagnosis of an immune-mediated disease: psoriasis (n=2), psoriatic arthritis (1), systemic lupus erythematosus (1), spondyloarthitis (1), rheumatoid arthritis (1) and skin lupus (1).Rheumatological side effects were observed in 15 patients (14.7%): inflammatory arthralgia (8), arthritis (6), myositis (2) and aortitis (1). The time of appearance of the rheumatological irAEs was of 6.36 months (±5.81). From the 7 patients with previous diagnosis of an immune-mediated disease, only 1 patient with psoriasis suffered a worsening of skin symptoms and another one with psoriatic arthritis had a monoarthritis episode.Among the 14 patients who suffered from arthralgia/arthritis, the most frequent pattern was oligoarticular (40%), followed by poly (30%) and monoarticular (30%). The most affected joint was the knee (n=4), followed by wrist (3), hands (3), ankle (2), shoulder (2) and foot (1).Apart from the articular disease, 2 patients suffered from myositis in lower limbs, with weakness of legs and arthralgia in their knees. A patient was diagnosed of aortitis through a PET, although the patient did not have any symptom.Immunology tests with RF, ACCP and ANA were done in 8 out of the 15 patients with musculoskeletal irAEs, being negative in all cases.Interviewing 40 of the patients who received ICBT, 7 of them (17.5%) referred xerophthalmia. 6 of them (15%) had a positive Schrimer test, and 3 (7.5%) had a reduced tear break-up time. None patient met Sjögren criteria.In 6 out of the 15 patients with rheumatological irAEs (all of them with arthralgia/arthritis) the ICBT was removed, temporary in all cases, and could be reintroduced after a mean of 33 ± 18.9 days. 6 patients were treated with NSAIDs and 5 with oral prednisone (2 of them also required intra-articular corticoids).ConclusionRheumatological irAEs are common in clinical practice. Arthralgia-Arthritis and dry-syndrome are the most frequent adverse events.Disclosure of InterestsLara Sánchez Bilbao: None declared, Iñigo González-Mazón: None declared, Rosalía Demetrio-Pablo: None declared, José Luis Martín-Varillas: None declared, Marina Delgado Ruiz: None declared, Isabel Bernat Piña: None declared, Belén ...