Health-related quality of life and utility outcomes with selinexor in relapsed/refractory diffuse large B-cell lymphoma.

Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT - Lymphoma (p ≤ 0.05), FACT - General (p < 0.05) and EuroQoL five-dimensions five-levels index scores (p < 0.001) beginning in cycle 3. The estimated difference in health state utilities for treatment response and progressive disease was both statistically significant and clinically meaningful (mean difference: 0.07; p = 0.001). Conclusion: In patients with relapsed/refractory diffuse large B-cell lymphoma, objective response to selinexor was associated with HRQoL maintenance, reduction in disease-related HRQoL decrements and higher health utilities.

Lay abstract This work examined quality of life (QoL) among patients with relapsed/refractory diffuse large B-cell lymphoma with two to five prior therapies who received single-agent selinexor in the SADAL clinical trial. Analysis of patient-reported Functional Assessment of Cancer Therapy ­ Lymphoma and EuroQoL five-dimensions five-levels data showed that patients who had objective clinical response to selinexor maintained their QoL over the course of treatment. Grade ≥3 adverse events and serious adverse events were not associated with clinically meaningful negative QoL impacts. Clinical trial registration: NCT02227251 (ClinicalTrials.gov).

Classification, prevalence, and outcomes of anticancer therapy-induced cardiotoxicity: the CARDIOTOX registry.

AIM: Cardiotoxicity (CTox) is a major side effect of cancer therapies, but uniform diagnostic criteria to guide clinical and research practices are lacking. METHODS AND RESULTS: We prospectively studied 865 patients, aged 54.7 ± 13.9; 16.3% men, scheduled for anticancer therapy related with moderate/high CTox risk. Four groups of progressive myocardial damage/dysfunction were considered according to current guidelines: normal, normal biomarkers (high-sensitivity troponin T and N-terminal natriuretic pro-peptide), and left ventricular (LV) function; mild, abnormal biomarkers, and/or LV dysfunction (LVD) maintaining an LV ejection fraction (LVEF) ≥50%; moderate, LVD with LVEF 40-49%; and severe, LVD with LVEF ≤40% or symptomatic heart failure. Cardiotoxicity was defined as new or worsening of myocardial damage/ventricular function from baseline during follow-up. Patients were followed for a median of 24 months. Cardiotoxicity was identified in 37.5% patients during follow-up [95% confidence interval (CI) 34.22-40.8%], 31.6% with mild, 2.8% moderate, and 3.1% with severe myocardial damage/dysfunction. The mortality rate in the severe CTox group was 22.9 deaths per 100 patients-year vs. 2.3 deaths per 100 patients-year in the rest of groups, hazard ratio of 10.2 (95% CI 5.5-19.2) (P < 0.001). CONCLUSIONS: The majority of patients present objective data of myocardial injury/dysfunction during or after cancer therapy. Nevertheless, severe CTox, with a strong prognostic relationship, was comparatively rare. This should be reflected in protocols for clinical and research practices.

Managing the front-line treatment for diffuse large B cell lymphoma and high-grade B cell lymphoma during the COVID-19 outbreak.

The COVID-19 pandemic has dramatically challenged care for cancer patients, especially those with active treatment who represent a vulnerable population for SARS-CoV-2 infection. Aggressive lymphoid neoplasms, such as diffuse large B cell lymphoma and high-grade B cell lymphoma, need to be treated without delay in order to get the best disease outcome. Because of that, our clinical practice was changed to minimise the risk of SARS-CoV-2 infection while continuing haematological treatment. In this report, we analyse the management of front-line therapy in 18 patients during the COVID-19 outbreak, as well as the results of the implemented measures in their outcome.

Comparative analysis of CAR T-cell therapy access for DLBCL patients: associated challenges and solutions in the four largest EU countries.

Introduction: CAR T-cell therapy has emerged as a promising new immuno-oncology treatment that engages the patient's immune system to fight certain hematological malignancies, including diffuse large B-cell lymphoma (DLBCL). In the European Union (EU), CAR T-cell therapies have been approved for relapsed/refractory (R/R) DLBCL patients since 2018, but patient access is often still limited or delayed. This paper is aimed at discussing challenges to access and possible solutions in the largest four EU countries. Methods: The analysis relied on literature review, market data collection, since homogeneous data coming from registries were not available, and discussion with experts coming from all four countries. Results: We calculated that in 2020, between 58% and 83% of R/R DLBCL patients (EMA approved label population) or between 29% and 71% of the estimated medically eligible R/R DLBCL patients, were not treated with a licensed CAR T-cell therapy. Common challenges along the patient journey that may result in limited access or delays to CAR T-cell therapy were identified. These include timely identification and referral of eligible patients, pre-treatment funding approval by authorities and payers, and resource needs at CAR T-cell centers. Discussion: These challenges, existing best practices and recommended focus areas for health systems are discussed here, with the aim to inform necessary actions for overcoming patient access challenges for current CAR T-cell therapies as well as for future cell and gene therapies.

Low Plasma Levels of Hyaluronic Acid Might Rule Out Sinusoidal Obstruction Syndrome after Hematopoietic Stem Cell Transplantation.

Background: Sinusoidal obstructive syndrome (SOS) is a potentially fatal complication secondary to hematopoietic stem cell transplant (HSCT) conditioning. Endothelial damage plasma biomarkers such as plasminogen activator inhibitor-1 (PAI-1), hyaluronic acid (HA), and vascular adhesion molecule-1 (VCAM1) represent potential diagnostic tools for SOS. Methods: We prospectively collected serial citrated blood samples (baseline, day 0, day 7, and day 14) in all adult patients undergoing HSCT at La Paz Hospital, Madrid. Samples were later analyzed by ELISA (enzyme-linked immunosorbent assay) for HA, VCAM1, and PAI-1 concentrations. Results: During sixteen months, we prospectively recruited 47 patients. Seven patients (14%) were diagnosed with SOS according to the EBMT criteria for SOS/VOD diagnosis and received treatment with defibrotide. Our study showed a statistically significant elevation of HA on day 7 in SOS patients, preceding clinical SOS diagnosis, with a sensitivity of 100%. Furthermore, we observed a significant increase of HA and VCAM1 levels on day 14. Regarding risk factors, we observed a statistically significant association between SOS diagnosis and the fact that patients received 3 or more previous lines of treatment before HSCT. Conclusions: The early significant increase in HA levels observed opens the door to a noninvasive peripheral blood test which could have the potential to improve diagnosis and facilitate prophylactic and therapeutic management of SOS before clinical/histological damage is established.

Cardiovascular risk factors during cancer treatment. Prevalence and prognostic relevance: insights from the CARDIOTOX registry.

AIMS: The actual usefulness of cardiovascular (CV) risk factor assessment in the prognostic evaluation of cancer patients treated with cardiotoxic treatment remains largely unknown. Prospective multicentre study in patients scheduled to receive anticancer therapy related with moderate/high cardiotoxic risk. METHODS AND RESULTS: A total of 1324 patients underwent follow-up in a dedicated cardio-oncology clinic from April 2012 to October 2017. Special care was given to the identification and control of CV risk factors. Clinical data, blood samples, and echocardiographic parameters were prospectively collected according to protocol, at baseline before cancer therapy and then at 3 weeks, 3 months, 6 months, 1 year, 1.5 years, and 2 years after initiation of cancer therapy. At baseline, 893 patients (67.4%) presented at least one risk factor, with a significant number of patients newly diagnosed during follow-up. Individual risk factors were not related with worse prognosis during a 2-year follow-up. However, a higher Systemic Coronary Risk Estimation (SCORE) was significantly associated with higher rates of severe cardiotoxicity (CTox) and all-cause mortality [hazard ratio (HR) 1.79 (95% confidence interval, CI 1.16-2.76) for SCORE 5-9 and HR 4.90 (95% CI 2.44-9.82) for SCORE ≥10 when compared with patients with lower SCORE (0-4)]. CONCLUSIONS: This large cohort of patients treated with a potentially cardiotoxic regimen showed a significant prevalence of CV risk factors at baseline and significant incidence during follow-up. Baseline CV risk assessment using SCORE predicted severe CTox and all-cause mortality. Therefore, its use should be considered in the evaluation of cancer patients.

[Clinical significance of the quantification of JAK2V617F allele burden in classical Ph-negative myeloproliferative neoplasms]. / Impacto clínico de la cuantificación de la carga mutacional de JAK2V617F en pacientes con neoplasias mieloproliferativas crónicas Ph negativas clásicas.

BACKGROUND AND OBJECTIVES: Our study has investigated the presence of the mutation V617F in the JAK2 gene in patients diagnosed with chronic myeloproliferative neoplasms (MPNs). Furthermore, we determined if JAK2 (V617F) allelic burden associates with a specific clinical phenotype and if its quantification can be used as a marker to predict outcome and complications in patients with MPNs. PATIENTS AND METHODS: A retrospective observational study was conducted from 1987 to 2011 in the Haematology Department of La Paz University Hospital. The allelic burden was measured in 114 patients diagnosed with MPNs: 39 polycythemia vera (PV) patients, 71 essential thrombocythaemia patients and 6 primary myelofibrosis patients. The quantitative real-time polymerase chain reaction (qRT-PCR) technology was used to determinate the percentage of mutated alleles in peripheral blood neutrophils. Patients were divided in 2 groups: heterozygous if the result was≤50% of the tested cells, and homozygous if it was positive in>50% of the cells. RESULTS: Sixty-nine patients were positive for the JAK2 mutation and 45 were negative. Among those positive, the mutation was associated with arterial thrombosis. In addition, we demonstrate in the homozygous group that the V617F mutation is associated to PV, advanced age, leukocytosis, marked haematopoiesis and splenomegaly. CONCLUSIONS: The presence of V617F mutation is associated with a higher incidence of thrombosis, leukocytosis and splenomegaly. The identification of mutation on the JAK2 gene could help in a better definition of evolution and prognostic stratification of the myeloproliferative disorders.