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Multiple myeloma (MM) is a heterogeneous disease. Evaluation of prognostic factors and risk stratification at diagnosis is necessary to compare outcome. Attempts have been made to apply a comorbidity score in the clinical sitting, but a standardized general approach is still lacking. We hypothesized that a comprehensive examination of every associated disease in a large cohort of patients could better highlight the prognostic impact of comorbidity in MM. All consecutive patients diagnosed in our institution, from 1993 to 2013, with symptomatic MM according to IMWG criteria were included in our population-based MM registry. Patients with plasma cell leukemia or with palliative management were excluded. Clinical variables analyzed were: age, sex, Durie-Salmon, International Scoring System (ISS), percentage of plasma cell in bone marrow by morphology (PC), serum creatinine (Cr) and estimated glomerular filtration rate according with Modification of Diet in Renal Disease (eGFR-MDRD). The following comorbodities were analysed: hypertension (HTA), diabetes (DM), obesity (OB) (body mass index > 30 Kg/m2), hyperlipaemia (HL), prior malignancy (PM), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), peptic ulcer (PU), thromboembolism (TE), renal transplant (RT), splenectomy (S), cutaneous disease (CD), amyloidosis (AM), heart disease (HD) (arrhythmia, congestive heart failure, coronary artery disease, other), lung disease (LD) (chronic obstructive pulmonary disease, asthma, other), liver disease (HE) (cirrhosis, non-alcoholic fatty liver disease, other), neurological disorder (ND), psychiatric disorder (PD) and rheumatologic disorder (RD). Kaplan-Meier method was used to estimate OS curves. Cox regression was used to determine the prognostic impact of each comorbidity in a univariate and multivariate model. 311 patients were eligible. Median age was 66 years (12-91), 148 men (47.6 %) and 163 women. Percentage of comorbidities was: HTA 45; OB 32.5; DM 20.4; HD 20.4; LD 15.2; PU 10; HL 9.7; ND 8; PM 7.8; PD 6.5; HBV 3.9; HE 3.9; TE 3.6; RD 3,5; AM 2.3; HCV 1.9; CD 1.6; S 1; RT 0.6; HIV 0.3. 63 patients (20.4 %) showed no comorbidities. Univariate analysis (table 1) demonstrated that AM (P=0.022), HCV (0.038), HIV (0.022), PD (0.015) and ND (0.05) were significantly associated with shorter OS. The variables associated with mortality in the multivariate analysis were age (p=0.002), ISS (III vs I: p=0.01), PC (p=0.05) and Cr (p=0.02). Results will be validated in another MM series and presented during the meeting. The overall prognosis of MM depends on a variety of host and disease-related characteristics. We confirm age, ISS, PC and Cr as robust and independent prognostic factors. Adjusting for these factors, no isolated comorbidity reach statistical significance; however, comorbidity seems to have a role in MM prognosis. More studies are warranted to define the prognostic impact of comorbidities in MM. Disclosures: No relevant conflicts of interest to declare.

Background:Early phase clinical trials (phases I / II) represent a key element in the process of translation of knowledge, obtained in basic research, towards its application in clinical practice. Phase I studies are designed to evaluate the drug's safety and toxicity at different dose levels and determine drug pharmacokinetics and pharmacodynamics. In contrast, phase II trials focus on clinical effectiveness. In some cases, phase I studies are perceived as a high risk procedure for the achievement of an uncertain benefit.Therefore, it seems appropriate to perform an analysis of the results obtained in early stage trials, in order to achieve a more objective risk/benefit assessment in this context.Aims:The main objective of the study was to analyze the safety and benefit of clinical trials in early stages in hematology. The results of overall survival (OS), progression free survival (PFS) and major toxicities between the phase I and phase II trials were compared.Methods:Data was extracted from medical histories of 262 patients with different hematological pathologies. These patients were admitted within one of the 66 phase I / II clinical trials opened between 2011 and 2018 at the Hospital 12 de Octubre. Data obtained was analyzed in terms of clinical response, toxicity and survival. We excluded 39 cases due to screening failure and 1 case due to withdrawal of the informed consent.Results:Considering the whole sample of patients, both in phase I (n = 77) and in phase II (n = 145), an overall response rate was verified (including complete and partial responses) in 66% of the patients. In 24% the disease remained stable and in 10% of cases it was refractory. The discontinuation rate of the studies in the whole series was 35.5%, mainly due to progression of the disease.Overall survival (OS) was 34.6 months, while the progression‐free survival (PFS) was 31.6 months. There were significant differences in PFS between the group of patients in phase I (22.5 months) and phase II (35.7 months) (p = 0.004), but there were no differences in OS (p = 0.405). 33,7% and 32,4% of patients enrolled in phase I and phase II studies died, respectively. The main cause of death was progression.Up to 39% of the patients included had some type of grade 3 or 4 toxicity, being hematological toxicity the most frequent(up to one third of the patients). In this regard, there were no significant differences between phase I and phase II trials, with 32.5% and 26.2% grade 3 or 4 toxicity, respectively.Summary/Conclusion:When comparing phase I and phase II trials, we found a higher PFS in phase II studies. This difference is probably due to the fact that part of the patients in phase I trials have received suboptimal doses of treatment, as the main objective of these studies is to warrant safety. However, when analyzing safety data, the differences between both groups in terms of grade 3 or higher toxicity are minimal and not statistically significant. In addition, there were no differences of OS between phase I and II trials.imageThere are few reports in this regard that can be used as a reference. However, the results obtained in our center offer a hopeful outlook in the future of therapeutics in Hematology, confirming the existence of a significant clinical benefit in patients included in early phase clinical trials.

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