The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701).

Background: Patient-reported outcomes (PROs) are becoming increasingly important in supporting clinical outcomes in clinical trials. In multiple myeloma (MM), PRO measurement is useful to reveal how treatment affects physical, psychosocial, and functional behaviour as well as symptoms and treatment-related adverse events to evaluate the benefit-risk ratio of a particular drug or drug combination. We report the types of PRO instruments used in MM, the frequency in which they are utilised in randomised controlled trials (RCTs), and the consistency of their reporting. Methods: The European Hematology Association (EHA) supports the development of guidelines for the use of PROs in adult patients with haematological malignancies. The first step is the present systematic review of the literature. MEDLINE and CENTRAL were searched for RCTs in MM between 2015 and 2020. Study design, characteristics of MM and its treatment, the primary outcomes, and the types of PRO instrument(s) were extracted using a predefined template. Additionally, in a stepwise approach, it was assessed whether the identified instruments had been validated for multiple myeloma patients, patients with haematological malignancies, or cancer patients. Results: Following screening for RCTs, 283 studies were included for review from 10,707 records retrieved, and 118 of these planned the use of PRO measures. Thirty-eight PRO instruments were reported. The most frequently used instrument (92 studies) was the EORTC QLQ-30. The EORTC-MY20 MM-specific questionnaire was the second most frequently used (50 studies), together with the EQ-5D (50 studies). Only 19 PRO instruments reported were consistent with the trial registry. Furthermore, in 58 publications, the information on PRO instruments differed between the publication and the trial registry. Further, information on PRO in HTA reports was available for 26 studies, of which 18 reports were consistent with the trial registries. Out of the 38 instruments used, six had been validated for patients with multiple myeloma (the most frequently used), six for patients with haematological malignancies, and 10 for cancer patients in general. Conclusions: The findings indicate that the measurement of PROs in RCTs for MM is underutilised, underreported, and often inconsistent. Guidelines for the appropriate use of PROs in MM are needed to ensure standardisation in selection and reporting. Furthermore, not all PRO instruments identified have been validated for myeloma patients or patients with haematological malignancies. Thus, guidelines for the appropriate use and reporting of PROs are needed in MM to ensure standardisation in the selection and reporting of PROs.

Background: It is quite obvious that population of new Hodgkin’s disease (HD) patients is heterogeneous in terms of clinical characteristics. Therefore stratification of patients is necessary to select appropriate treatment regimen. It was shown that new lymphoma patient population is heterogeneous in terms of base-line QoL (Novik A et al, 2003). The aim of the study was to identify if new HD patients are heterogeneous in terms of QoL and to stratify patients using QoL parameters. Patients and methods: 114 new HD patients (stage IIB-IV, mean age 30.2 (SD 13.5), males/females - 55/59) were enrolled in the study. Patients filled in EORTC QLQ-C30 at baseline. The method of integral profiles (MIP) was used to calculate integral QoL index (IQL), the coefficient of QoL deformation (CQLD) and the index of symptom severity (ISS). The above indexes were used for stratification by the cluster analysis (Ward method, percent of cases correctly classified - 98.25%). Discriminant analysis was performed for stratification testing. Results: Three groups of HD patients were identified after stratification. IQL, CQLD and ISS were as follows: subgroup 1 (n=5, mean age 40.8 (22.9), male/female 1/4) − 0.04, 1.7, 0.17; subgroup 2 (n=47, mean age 34.3 (14.5), male/female 23/24) − 0.35, 0.62, 0.09; subgroup 3 (n=62; mean age 26.0 (9.7); male/female 31/31) − 0.74, 0.24, 0.01. Group 1 has the worst QoL and is characterized by low IQL, pronounced symptoms and high deformation of QoL profile. Group 3 has the best QoL with high IQL, weak symptoms and low deformation of QoL profile. Group 2 has intermediate values of above parameters. Differences between groups were significant (p<0.05) by ANOVA. Conclusion: The method of integral profiles to obtain the integral QoL index and the coefficient of QoL deformation in HD patients is proposed. Stratification of new HD patients by cluster analysis resulted in three patient subgroups according to their QoL data. Identification of subgroups of HD patients on the basis of their QoL has a good potential for better stratification of new HD patients and in doing so might be used for improvement of the intervention strategies.

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Background:The efficacy of chimeric antigen receptor (CAR) modified T cells against CD30 (CAR30) in Hodgkin Lymphoma (HL) is limited by the suppressive tumor microenvironment (TME). Combined therapy of CAR30 with PD-1/PD-L1 MoAb may increase cure rates but remains to be proved. Boosting the in vivo expansion of infused CAR-T cells and increasing cytokines release may also improve the clinical outcomes. In addition, eliminating B cells from TME may disrupt the essential interactions of tumor survival. We previously developed a CAR-T cell product targeting on CD22, and simultaneously secreting an anti-PDL1 ScFv construct (CAR22p). Preclinical data showed that CAR22p have stronger lytic activity and higher cytokines production when reacting with CD22+PDL1+ tumor line in comparison to CAR22. Aims: We conduct a pilot study (NCT03121625) to investigate the safety and efficacy of a dual transduced CAR-T cell, both CAR30 and CAR22p, for r/r HL patients. Methods: The constructs of CAR30 and CAR22p are shown in Fig 1. CAR30 includes a truncated EGFR sequence, can be used to identify and select CAR positive cells. CAR22p includes a ScFv sequence derived from a MoAb against human PD-L1. T cells stimulated by a-CD3x-CD28 beads are dual transduced with CAR30 and CAR22p. Transduced cells are expanded in serum free media formulation with IL-2, −7 and −15. Percentages of CAR30+ and CAR22p+ T cells were determined by flow cytometry through staining with antibodies against EGFR and CD22-Fc. Real-time Q-PCR using primers with specificity for the ScFvs of CAR30 and CAR22p can detect the in vivo CAR-T persistence for either CAR. After lymphodepleting chemotherapy, products are infused at the protocol-prescribed dose level.Results: Four subjects (ages 12-31 yr) with heavily pre-treated cHL have been treated in this trial. All therapy was well tolerated. There were no grade 3 or 4 treatment-related adverse events. The most common toxic-

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Objectives: HDCT+ASCT is a new and promising therapy for MS patients. Among a number of questions are the terms of conducting HDCT+ASCT. According to our concept there are 3 strategies of HDCT+ASCT depending on terms of disease stage: early, conventional and salvage. The aim of the research was to study clinical and quality of life (QoL) outcomes in MS patients with different terms of HDCT +ASCT. Methods: Twelve patients with MS were included in the study. All the patients previously underwent conventional treatment. Clinical and QoL evaluation was provided at baseline, at discharge, at 3, 6, 9, 12 months and later every half a year after HDCT+ ASCT. MRI was conducted at baseline, in 6, 12 months and at the end of follow-up. QoL was assessed by FACT-BMT and FAMS. Integral QoL index was assessed by the method of integral profiles. Median EDSS at base-line was 6.0 (range 2 –7.5). The median follow-up duration was 18 months (range 3–60 months). Results: Clinical examination and MRI revealed disease stabilization (DS) in ten patients and progression (DP) in two patients. EDSS decreased in seven patients; increased from 6.5 to 7.0 and from 6.0 to 6.5 in patients with DP and remained the same in three patients. Distinct QoL improvement was observed in all the patients with DS at the end of follow-up. Three case reports with different terms of ASCT were analyzed. Patient K. underwent early ASCT (male, 21 years old; secondary progredient type; base-line EDSS - 2.0; follow-up 18 months); patient F.- conventional ASCT (female, 35 years old; secondary progredient type; base-line -EDSS 5.0; follow-up 60 months); patient P.- salvage ASCT (female, 49 years old; secondary progredient type; base-line EDSS 7.5; follow-up 48 months). Clinical examination and MRI revealed DS. EDSS decreased from 2.0 to 1.5 in patient K.; from 5.0 to 4.5 in patient F. and from 7.5 to 6.0 in patient P. at the end of follow-up. Integral QoL index increased dramatically as compared to base-line: in patient K. - from 0.6 to 0.7; in patient F. - from 0.2 to 0.7; in patient P. - 0.4 to 0.6. Conclusion: HDCT+ASCT in MS patients resulted in DS in ten out of twelve patients under observation. Along with clinical stabilization dramatic improvement of QoL took place. Analysis of three case reports demonstrated feasibility of early, conventional and salvage ASCT in MS patients.

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