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Background aMM still represents a hard-to treat disease, due to its rarity and to the modest activity of standard chemotherapy. Recently, ICIs directed against PD-1/PD-L1 have been tested in clinical trials in chemotherapy pre-treated aMM patients, but their efficacy is still debatable. Methods We searched PubMed and proceedings of major meetings, to perform a systematic review and meta-analysis (updated at September 30th 2019) of clinical trials testing ICIs in this setting, describing activity in terms of Objective Response Rate (ORR) and Disease Control Rate (DCR). To explore the potential predictive role of PD-L1 expression, we also collected the ORR in subgroups of patients selected for PD-L1 expression (based on the highest cut-off used in each study). Results 8 studies were selected (1 phase III, 4 phase II, 2 phase IB, 1 real-world EAP data study), including 405 patients, most with pleural MM; 1 registry study was excluded due to inclusion of treatment-naive patients, 1 due to unclear inclusion criteria. 352 patients (87%) were treated with anti-PD-1 (nivolumab [N] or pembrolizumab [P]), 53 (13%) with anti-PD-L1 (avelumab [A]). Overall, ORR was 19.6% (95% CI, 16.0-23.8%) with no significant difference among drugs (N 20.0%, P 22.6%, A 9.4%; p = 0.11); DCR was 56.5% (95% CI, 51.6-61.3%) with no significant difference among drugs (N 54.0%, P 58.7%, A 58.5%; p = 0.66). When restricting the analysis to patients selected for PD-L1 expression (n evaluable=91, based on cut-offs ranging from 1% to 50% in different trials), ORR was 34.1% (95% CI, 25.2-44.3%), ranging from 18.8% to 71.4% in different trials. In unselected patients, median progression-free survival ranged from 2.5 to 6.1 months, and median overall survival ranged from 6.36 to 17.3 months. Conclusion To our knowledge, this is the first meta-analysis synthesizing the evidences of activity of PD-1/PD-L1 ICIs in pre-treated aMM. ORR and DCR in unselected patients are encouraging compared to historical results with second-line chemotherapy. Selection based on PD-L1 expression could increase the activity of immunotherapy, but trials were heterogeneous for test and cut-off. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure M. Tagliamento: Travel / Accommodation / Expenses: Takeda, Bristol-Myers Squibb, Roche. P. Bironzo: Honoraria (self): Bristol-Myers Squibb, BI, AstraZeneca. E. Capelletto: Advisory / Consultancy: BI, AstraZeneca. S. Novello: Speaker Bureau / Expert testimony: AstraZeneca, Abbvie, Celgene, BI, Bristol-Myers Squibb, MSD, Eli Lilly, Pfizer, Roche. M. Di Maio: Honoraria (self): Bristol Myers Squibb, Merck Sharp & Dohme, Roche, AstraZeneca, Janssen, Takeda, Pfizer; Honoraria (institution): Tesaro. All other authors have declared no conflicts of interest.

Introduction Venous thromboembolism (VTE) is one of the leading cause of death for cancer pts, with an incidence of 1 event per 110-120 patients, mainly within the first year from diagnosis. Cancer pts with VTE show a 2.2-fold increase in mortality and lung cancer is the second tumor type with the highest incidence of VTE. Considering that chemotherapy is associated with a 6 times increased risk of VTE and that biological agents, especially antiangiogenetic compounds, cause an additional risk, the aim of the study is to evaluate, with a radiological retrospective evaluation, the real incidence of PE in selected cohorts of advanced NSCLC patients and the impact of PE on survival. Materials and methods This retrospective monocentric study enrolled 141 advanced NSCLC pts, diagnosed between June 2007 and June 2008 (cohort 1), and between January 2010 and December 2010 (cohort 2). Pts were mostly men, with a median age of 63 years, performance status of 0 and a prevalence of comorbidities predisposing to VTE of 42.0% and 70.0% in first and second cohort, respectively. 74.1% and 43.3% of pts received biological agents in first and second cohort; 39.5% and 21.7% antiangiogenetic agents. Results Retrospective review of 460 contrast-enhanced multidetector computed tomography studies showed a prevalence of PE of 13.6% in the first cohort and of 15.0% in the second one. Survival analysis didn't show any statistically significant differences in terms of OS and TTP in the first cohort. In the second cohort, Kaplan Meier curves showed a significantly difference in terms of TTP in favor of pts who never developed PE, p-value = 0.003. Similar results were observed considering as stratification factors the use of biological agents, p-value = 0.007, and of antiangiogenic agents, p-value = 0.010. Conclusion The higher incidence of PE in the second cohort, despite a lower exposure to biological and antiangiogenic agents, could be related to a greater thrombogenic action of these drugs, but also a higher prevalence of comorbidities predisposing to VTE. Descriptive analysis was confirmed by survival data, underlining the need of further studies to clarify the role of predisposing factors for PE. Disclosure All authors have declared no conflicts of interest.

Introduction Pemetrexed (Pem) has been approved for the treatment of advanced non small cell lung cancer (NSCLC) non-squamous histology, both as 1° and 2° line therapy with or without platinum compounds, respectively. Pem is an antimetabolite drug, that inhibits enzymes involved in nucleotides bio-synthesis arresting cancer cells cycle. Literature data show the effect of antimetabolities on increment of erythrocyte mean corpuscolar volume (MCV) in cancer patients (pts) treated with capecitabine and, recently, a positive correlation between increased MCV and response to capecitabine-based therapy has emerged [Arslan et al, Tumori 2011; Dellapasqua et al, Breast 2012]. The aim of this study was the evaluation of the impact of Pem on MCV change and its possible correlation with disease control rate (overall response + stable disease rate) (DCR), progression free survival (PFS) and overall survival (OS) in NSCLC pts. Methods A retrospective collection of clinical and laboratory data (including basal MCV and maximum MCV occurred during Pem therapy) in 165 advanced NSCLC pts treated with Pem from 4 Italian centres was performed. Results Pts characteristics: 59% men, median age 64 years (range 36-83), 58% ECOG PS 0, 90% stage IV and 10% stage IIIB (according 6th TNM), 87% adenocarcinoma histotype, 74% current or ex-smokers, 59% as 1° line, 41% as ≥ 2° line, 68% in combination with a platinum compound, median cycle 4 (range 1-29). All pts received vitamin B12 and folic acid supplementation. Mean MCV significantly increased from basal (89.6 fl) to “during treatment” (94.8 fl), with mean ΔMCV = 5.2 fl (t test for paired data, p 5 fl (n = 68) and in ΔMCV ≤ 5 fl (n = 97) pts, respectively. Conclusion Pem induces significant increase of erythrocyte MCV. ΔMCV > 5 fl on Pem therapy appears to be correlated with better DCR, PFS and OS. These data should be related to a decreased metabolism of Pem and subsequent increased drug exposure in pts who develop higher ΔMCV during treatment. A larger prospective evaluation could be useful to better clarify these findings. Disclosure All authors have declared no conflicts of interest.