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Este trabajo se centra en el análisis sobre los conocimientos, habilidades y necesidades empresariales en el ámbito de la contabilidad y la administración de empresas. También, y de forma más general, se abordan otras parcelas de la información financiera y no financiera o en materia de sostenibilidad, buscando analizar el grado de empleabilidad, mejora y utilidad para los estudiantes que se han formado en las materias citadas. El trabajo se estructura en cuatro partes: revisión del marco teórico del trabajo y sus antecedentes; metodología y descripción de la muestra; análisis de los resultados de la investigación, y conclusiones alcanzadas. La parte empírica del mismo se ha desarrollado eligiendo como población los alumnos/as (egresados/as) que han realizado los estudios de las materias seleccionadas en el Grupo Educativo CEF.- UDIMA. Las respuestas recibidas nos han permitido hacer estimaciones con un nivel de confianza de al menos el 90% y con un error muestral máximo del 5%. Algunas de las evidencias obtenidas destacan que la mayoría de los/as encuestados/as (94,12%) trabaja actualmente en alguna actividad relacionada con los estudios realizados en las materias citadas; más del 60% ha mejorado, en un corto espacio de tiempo, su posición tras la finalización de los estudios o ha conseguido un empleo; el 75% considera que los conocimientos adquiridos durante la titulación le han permitido desarrollar su trabajo, manifestando estar satisfechos/as o muy satisfechos/as con su puesto de trabajo (con una puntuación media de 3,97 sobre 5) o que valoran de manera muy positiva (4,17 sobre 5) la formación recibida en contabilidad, así como en información no financiera. 2021-22

Hodgkin lymphoma (HL) patients who relapse after autologous-stem-cell- transplantation (auto-SCT) have traditionally had a poor prognosis. We analyzed 1781 adult HL patients who relapsed between 2006 and 2017 after a first auto-SCT. The 4-year overall survival (OS) after relapse continuously increased from 32% for patients relapsing in 2006-2008, to 63% for patients relapsing in 2015-2017 (p = 0.001). The improvement over time was predominantly noted in patients who had an early relapse (within 12 months) after auto-SCT (p = 0.01). On multivariate analysis, patients who relapsed in more recent years and those with a longer interval from transplant to relapse had a better OS, whereas increasing age, poor performance status, bulky disease, extranodal disease and presence of B symptoms at relapse were associated with a worse OS. Brentuximab vedotin (BV), checkpoint inhibitors (CPI) and second transplant (SCT2; 86% allogeneic) were used in 233, 91 and 330 patients respectively. The 4-year OS from BV, CPI, and SCT2 use was 55%, 48% and 55% respectively. In conclusion, the outcome after post-transplant relapse has improved significantly in recent years, particularly in the case of early relapse. These large-scale real-world data can serve as benchmark for future studies in this setting.

Supplementary Figure 2 from MicroRNAs Are Independent Predictors of Outcome in Diffuse Large B-Cell Lymphoma Patients Treated with R-CHOP

Supplementary Figure 1 from MicroRNAs Are Independent Predictors of Outcome in Diffuse Large B-Cell Lymphoma Patients Treated with R-CHOP

Purpose: Diffuse large B-cell lymphoma (DLBCL) heterogeneity has prompted investigations for new biomarkers that can accurately predict survival. A previously reported 6-gene model combined with the International Prognostic Index (IPI) could predict patients' outcome. However, even these predictors are not capable of unambiguously identifying outcome, suggesting that additional biomarkers might improve their predictive power.Experimental Design: We studied expression of 11 microRNAs (miRNA) that had previously been reported to have variable expression in DLBCL tumors. We measured the expression of each miRNA by quantitative real-time PCR analyses in 176 samples from uniformly treated DLBCL patients and correlated the results to survival.Results: In a univariate analysis, the expression of miR-18a correlated with overall survival (OS), whereas the expression of miR-181a and miR-222 correlated with progression-free survival (PFS). A multivariate Cox regression analysis including the IPI, the 6-gene model–derived mortality predictor score and expression of the miR-18a, miR-181a, and miR-222, revealed that all variables were independent predictors of survival except the expression of miR-222 for OS and the expression of miR-18a for PFS.Conclusion: The expression of specific miRNAs may be useful for DLBCL survival prediction and their role in the pathogenesis of this disease should be examined further. Clin Cancer Res; 17(12); 4125–35. ©2011 AACR.

Supplementary Figure Legends 1-2 from MicroRNAs Are Independent Predictors of Outcome in Diffuse Large B-Cell Lymphoma Patients Treated with R-CHOP

Background: RIC-alloHSCT had been our standard of care for patients more than 50, with comorbidities or previously transplanted. Methods: 484 consecutive RIC-alloHSCT were included. GVHD prophylaxis consisted of CsA-MTX(147), CsA-MMF(124), tacro-siro(145) and PTCy-tacro(68). Results: The median time of overall follow-up in survivors was 8-years (with at least 3-years in all four GVHD prophylaxis groups).Neutrophil and platelet engraftment was longer for PTCy-tacro (p0.0001). CumInc of grade III-IV aGVHD was 17% at 200 days and of moderate-severe cGvHD was 36% at 8-years. GVHD prophylaxis was the only prognostic factor in the MVA(p0.0001). NRM and relapse were 29% and 30%; OS and PFS were 43% and 39% at 8-years. At 3-years, OS was highest in the PTCy-tacro (68%) than in the tacro-siro (61%) and CsA+MTX/MMF (49%) cohorts (PConclusion: This large single institution experience shows the improvement of RIC-alloHSCT over time, mainly due to a better prevention of acute and chronic GVHD. Based on our recent results we strongly support PTCy as the current standard of care since in our hands associates to the best 3-year survival.

International audience; Intratumoral injection of G100, a toll-like receptor 4 (TLR4) agonist, was shown pre-clinically to stimulate anti-tumor immune responses and tumor regression. This open-label, multicenter, phase 1/2 trial evaluated the safety, tolerability, and preliminary efficacy of intratumoral G100 injections following localized low-dose radiation in patients with follicular lymphoma (ClinicalTrials.gov #NCT02501473). The study was comprised of a G100 dose escalation (5 or 10 mu g/dose, or 20 mu g/dose for large tumors); a randomized component comparing G100 to G100 plus pembrolizumab; and G100 20 mu g/dose expansion. Adverse events grade >= 3 were uncommon in patients treated with G100, and no unexpected toxicities were observed when combined with pembrolizumab. G100 20 mu g (n = 18) resulted in an overall response rate of 33.3% and abscopal tumor regression in 72.2% of patients. This early-phase study provides a foundation for combining an intratumoral TLR4 agonist with agents to produce immune-mediated responses in follicular lymphoma with limited added toxicity.

Key Points BET inhibitor RO6870810+venetoclax+rituximab has a manageable safety profile in relapsed/refractory diffuse large B-cell lymphoma.A clinically relevant signal of antitumor activity serves as a proof of principle for this combination, warranting further study., Visual Abstract, Bromodomain and extraterminal (BET) proteins are transcriptional activators for multiple oncogenic processes in diffuse large B-cell lymphoma (DLBCL), including MYC, BCL2, E2F, and toll-like receptor signaling. We report results of a phase 1b dose-escalation study of the novel, subcutaneous BET inhibitor RO6870810 (RO) combined with the BCL-2 inhibitor venetoclax, and rituximab, in recurrent/refractory DLBCL. RO was delivered for 14 days of a 21-day cycle, whereas venetoclax was delivered continuously. A 3 + 3 escalation design was used to determine the safety of the RO+venetoclax doublet; rituximab was added in later cohorts. Thirty-nine patients were treated with a median of 2.8 cycles (range, 1-11). Dose-limiting toxicities included grade 3 febrile neutropenia, grade 4 diarrhea, and hypomagnesemia for the doublet; and grade 3 hyperbilirubinemia and grade 4 diarrhea when rituximab was added. The doublet maximum tolerated dose (MTD) was determined to be 0.65 mg/kg RO+600 mg venetoclax; for RO+venetoclax+rituximab, the MTDs were 0.45 mg/kg, 600 mg, and 375 mg/m2, respectively. The most frequent grade 3 and 4 adverse events were neutropenia (28%) and anemia and thrombocytopenia (23% each). Responses were seen in all cohorts and molecular subtypes. Sustained decreases in CD11b on monocytes indicated pharmacodynamic activity of RO. Overall response rate according to modified Lugano criteria was 38.5%; 48% of responses lasted for ≥180 days. Complete response was observed in 8 patients (20.5%). Optimization of the treatment schedule and a better understanding of predictors of response would be needed to support broader clinical use. This trial is registered on www.clinicaltrials.gov as NCT03255096.

This is a randomized phase-2 trial aimed to compare consolidation vs. maintenance in untreated patients with follicular lymphoma (FL) responding to induction. 146 patients were enrolled from 25 Spanish institutions (ZAR2007; ClinicalTrials.gov #NCT00662948). Patients in PR or CR/CR[u] after R-CHOP were randomized 1:1 to 90Y-ibritumomab-tiuxetan 0.4 mCi/kg (arm A) vs. rituximab 375 mg/m2 every 8 weeks for 2 years (arm B). After a median follow-up of 10.55 years, 53 patients eventually progressed with a 10-year PFS of 50% vs. 56% for patients in arm A and B, respectively (HR = 1.42; p > 0.1). No significant differences were seen in OS (10-year OS 78% vs. 84.5%; HR = 1.39, p > .1). Patients receiving 90Y-ibritumomab-tiuxetan showed higher incidence of second neoplasms than those in arm B (10-year cumulative incidence 18.5 vs. 2%, respectively; p = .038). In conclusion, in FL patients responding to R-CHOP, no significant differences were found between consolidation and maintenance, although with higher late toxicity for consolidation.

Tisagenlecleucel (tisa‐cel) is a second‐generation autologous CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy approved for relapsed/refractory (R/R) large B‐cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa‐cel in the standard‐of‐care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa‐cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded according to ASTCT criteria and responses were assessed as per Lugano 2014 classification. Of 91 patients who underwent leukapheresis, 75 (82%) received tisa‐cel therapy. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 5% and 1%, respectively; non‐relapse mortality was 4%. Among the infused patients, best ORR and CR were 60% and 32%, respectively, with a median duration of response of 8.9 months. With a median follow‐up of 14.1 months from CAR T‐cell infusion, median progression‐free survival and overall survival were 3 months and 10.7 months, respectively. At 12 months, patients in CR at first disease evaluation had a PFS of 87% and OS of 93%. Patients with an elevated lactate dehydrogenase showed a shorter PFS and OS on multivariate analysis. Treatment with tisa‐cel for patients with relapsed/refractory LBCL in a European SOC setting showed a manageable safety profile and durable complete responses., This article provides real‐world European data on the results of relapsed/refractory large B‐cell lymphoma patients treated with tisagenlecleucel.

Identifying factors that ameliorates clinical outcomes following CART therapy represents an unmet need. We hypothesized that CAR expression level would have a significant impact on CART efficacy and tested this with CAR30(+) T-SCM(-)LIKE enriched cells. By sorting T-cells according to CAR mean fluorescence intensity in two markedly different populations (CAR(HI) and CAR(LO)), we showed that a high CAR expression enhances antitumor efficacy in vitro, that is sustained after sequential re-exposures to tumor cells and is not associated with T-cell exhaustion or differentiation. Furthermore, we found a correlation between high surface CAR expression and antitumor effect with CAR19(+) T-cells, thus validating our findings with CAR30. Definitive proof of CAR(HI) T-cells improved antitumor efficacy was demonstrated in a human Hodgkin's lymphoma xenograft mouse model, where CAR30-T-SCM(-)LIKE enriched products with high intensity of CAR expression achieved superior tumor control in vivo and longer survival than those with a low intensity of CAR expression. Our data suggest that modulation of CAR intensity of expression represents an additional strategy to increase CART therapy clinical efficacy.

Background Advanced-stage mycosis fungoides/Sezary syndrome (aMF/SS) has a dismal outcome. The only curative treatment is allogeneic stem cell transplantation (allo-SCT) but this is limited to selected candidates, thus palliative therapy is the most frequent strategy. Objectives To describe the characteristics of aMF/SS in cases referred to haematology units for advanced/palliative therapy. Materials and Methods Data from 30 patients were collected from four centres, and descriptive statistics, frequencies and survival analyses were calculated. Results Eighty-eight per cent of patients received systemic therapy. The median number of therapies was three (range: 1-9). Bexarotene (21%), CHOP-like chemotherapy (10%) and methotrexate (9%) were the more common treatments. The overall survival at a median follow-up of 28 months (range: 8-65 months) for aMF/SS was 56.9%. Survival probability was more favourable for MF (p < 0.02). Nine patients received allo-SCT. Half of the patients (56%) relapsed after allo-SCT but could be rescued with immunosuppression tapering, donor lymphocyte infusions and additional therapy (80%). Conclusion There is significant heterogeneity in aMF/SS treatments. Survival is more favourable for MF compared to SS. Current chemoimmunotherapies are insufficient to control disease, making allo-SCT the best therapeutic approach in selected patients

The purpose of this report is to provide long-term follow-up of 38 patients diagnosed of post-transplant lymphoproliferative disease (PTLD) included in a phase 2 clinical trial of first line therapy with rituximab and to evaluate the same therapy in a real world cohort of 21 consecutive patients treated once the trial was closed. Eligible patients were ≥ 18 years of age with a biopsy-proven CD20 positive B cell PTLD and treatment naive except for reduction of immunosuppression. Treatment consisted in four weekly infusions of rituximab at the standard dose of 375 mg/m2. Patients in complete remission (CR) were followed without further treatment, and those in partial remission (PR) were treated with another four cycles of weekly rituximab. Median follow-up in the clinical trial was 13.0 years. Disease-specific survival (DSS) at 10 years was 64.7% [95% confidence interval (CI) 48.2–81.2%]. For those patients who achieved CR (61%), DSS at 5 and 10 years was 94.4% (95% CI 83.8–100%) and 88.1% (95% CI 72.6–100%), respectively, and only 1 patient progressed beyond 5 years. The median follow-up of the real world patients was 6.5 years. DSS at 5 years was 75.2% (95% CI 56.4–94.0%). DSS at 5 years of patients who achieved CR (38%) was 87.5% (95% CI 64.6–100%). In conclusion, PTLD patients in CR after rituximab have an excellent long-term outcome. These results not only apply in the clinical trial setting but are also reproducible in the real world. However, those patients who do not respond represent an unmet clinical need and should be included in prospective clinical trials.

Background: Recent advances in the treatment of non-Hodgkin lymphoma (NHL) have transformed the landscape and provided significant benefits to patients. Novel agents that target CD19 and CD20 on B cells, such as bispecific T-cell engagers and chimeric antigen receptor T-cell (CAR-T) therapy, have demonstrated benefit for patients in the relapsed and refractory setting. However, these agents can often be associated with significant toxicity and there is a need for new therapies that can provide clinical benefit with a superior safety profile. Imvotamab is a novel CD20 x CD3 bispecific antibody utilizing an IgM backbone. This allows targeting of up to 10 CD20 binding sites for every CD3 site. In preclinical models, imvotamab demonstrated encouraging antitumor activity and stimulated T-cells in a more physiologic manner than IgG-based antibodies, which may reduce adverse events typically associated with T-cell engagers and CAR-T, such as CRS and neurotoxicity. Loncastuximab tesirine is a CD19-targeting antibody-drug conjugate approved by the US FDA and EMA for relapsed DLBCL after 2 lines of systemic therapy. Loncastuximab tesirine has shown activity in both DLBCL and FL. Combining therapies such as loncastuximab tesirine, which targets CD19 and induce apoptosis of cancer cells, with imvotamab’s ability to eliminate CD20+ tumor cells by engagement with T-cells, may improve treatment outcomes among patients with NHL via synergistic mechanisms of action. Methods: This study is a Phase 1/2, multicenter, single-arm clinical trial of imvotamab as monotherapy and in combination with loncastuximab tesirine for patients with relapsed/refractory NHL. Phase 1a Dose Escalation is complete with no DLTs or neurotoxicity AEs up to 1000mg dose titration. Phase 1b Combination will evaluate imvotamab and loncastuximab tesirine in patients with R/R 2nd line or later NHL. Phase 2 monotherapy Dose Selection is currently ongoing. The Phase 2 component randomizes patients at two different dose levels (100 mg and 300 mg plateau dose) in two separate indications (R/R DLBCL and R/R FL). Patients receive weekly dosing on Day 1, 8, and 15 of each 21- day cycle. Dosing begins at 15 mg and is increased weekly for 3-4 weeks to reach the plateau dose. Patients then stay at the plateau dose until disease progression or unacceptable toxicity. Patients who achieve a response by Week 12 may switch to a less frequent dosing interval of every 3 weeks. Primary endpoints include frequency and severity of adverse events and objective response rate (ORR) based on Lugano criteria. Correlative biomarker studies will evaluate the relationship of clinical benefit with blood and tissue biomarkers. The study is currently open with patients enrolling in Phase 2 at time of submission. Phase 1b Combination is expected to begin enrollment in the first quarter of 2023. Clinical trial information: NCT04082936. Citation Format: Catherine Diefenbach, Won Seog Kim, Chan Cheah, Ajay K. Gopal, Philippe Armand, Ian Flinn, Gareth P. Gregory, Sung-Soo Yoon, Loretta Nastoupil, Jennifer Lue, Vincent Ribrag, Javier Briones, Antonio Salar-Silvestre, Anna Sureda-Balari, Matthew Ku, Hans Cruz, Paul Thaler, Ibrahim Qazi, Rachel Wei, Maya Leabman, Genevive Hernandez, Iris Sison, Elizabeth Budde. A phase 1/2 randomized study of imvotamab monotherapy and in combination with loncastuximab tesirine in relapsed/refractory non-Hodgkin lymphomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT052.

Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) cases have a poor outcome. Here we analysed clinico-biological features in 373 DLBCL patients homogeneously treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP), in order to identify variables associated with early failure to treatment (EF), defined as primary refractoriness or relapse within 12 months from diagnosis. In addition to clinical features, mutational status of 106 genes was studied by targeted next-generation sequencing in 111 cases, copy number alterations in 87, and gene expression profile (GEP) in 39. Ninety-seven cases (26%) were identified as EF and showed significantly shorter overall survival (OS). Patients with B symptoms, advanced stage, high levels of serum lactate dehydrogenase (LDH) or beta 2-microglobulin, low lymphocyte/monocyte ratio and higher Revised International Prognostic Index (R-IPI) scores, as well as those with BCL2 rearrangements more frequently showed EF, with R-IPI being the most important in logistic regression. Mutations in NOTCH2, gains in 5p15 center dot 33 (TERT), 12q13 (CDK2), 12q14 center dot 1 (CDK4) and 12q15 (MDM2) showed predictive importance for EF independently from R-IPI. GEP studies showed that EF cases were significantly enriched in sets related to cell cycle regulation and inflammatory response, while cases in response showed over-representation of gene sets related to extra-cellular matrix and tumour microenvironment.

Rituximab plus chemotherapy induction followed by rituximab maintenance for up to 2 years confers a long-term benefit in terms of progression-free survival in patients with indolent non-Hodgkin lymphoma. It is not known whether further prolonged maintenance with rituximab provides additional benefit. The phase III MabCute study enrolled 692 patients with relapsed or refractory indolent non-Hodgkin lymphoma. Patients who responded to induction with rituximab plus chemotherapy and were still responding after up to 2 years’ initial maintenance with subcutaneous rituximab were randomized to extended maintenance with subcutaneous rituximab (n=138) or observation only (n=138). The primary endpoint of investigator-assessed progression-free survival in the randomized population was un-addressed by the end of study because of an insufficient number of events (129 events were needed for 80% power at 5% significance if approximately 330 patients were randomized). In total, there were 46 progression-free survival events, 19 and 27 in the rituximab and observation arms, respectively (P=0.410 by stratified log-rank test; hazard ratio 0.76 [95% confidence interval: 0.37– 1.53]). The median progression-free survival was not reached in either randomized arm. There were no new safety signals; however, adverse events were seen slightly more frequently with rituximab than with observation during extended maintenance. Maintenance for up to 2 years with rituximab after response to initial induction therefore remains the standard of care in patients with relapsed or refractory indolent non- Hodgkin lymphoma. (Clinicaltrials.gov identifier: NCT01461928).

The frequency of aggressive subtypes of B-cell non-Hodgkin lymphoma (B-NHL), such as high-grade B-cell lymphomas (HGBL) with MYC and BCL2 and/or BCL6 rearrangement (HGBL-DH/TH) or Burkitt-like lymphoma (BL) with 11q aberration, is not well known in the HIV setting. We aimed to characterise HIV-associated aggressive B-NHL according to the 2017 WHO criteria, and to identify genotypic and phenotypic features with prognostic impact. Seventy-five HIV-associated aggressive B-NHL were studied by immunohistochemistry (CD10, BCL2, BCL6, MUM1, MYC, and CD30), EBV-encoded RNAs (EBERs), and fluorescence in situ hybridisation (FISH) to evaluate the status of the MYC, BCL2, and BCL6 genes and chromosome 11q. The 2017 WHO classification criteria and the Hans algorithm, for the cell-of-origin classification of diffuse large B-cell lymphomas (DLBCL), were applied. In DLBCL cases, the frequencies of MYC and BCL6 rearrangements (14.9 and 27.7%, respectively) were similar to those described in HIV-negative patients, but BCL2 rearrangements were infrequent (4.3%). MYC expression was identified in 23.4% of DLBCL cases, and coexpression of MYC and BCL2 in 13.0%, which was associated with a worse prognosis. As for BL cases, the expression of MUM1 (30.4%) conferred a worse prognosis. Finally, the prevalence of HGBL-DH/TH and BL-like with 11q aberration are reported in the HIV setting. The phenotypic and genotypic characteristics of HIV-associated aggressive B-NHL are similar to those of the general population, except for the low frequency of BCL2 rearrangements in DLBCL. MYC and BCL2 coexpression in DLBCL, and MUM-1 expression in BL, have a negative prognostic impact on HIV-infected individuals.