Impact of age and comorbidities on the efficacy and tolerability of bosutinib in previously treated patients with chronic myeloid leukemia: results from the phase 4 BYOND study.

In the phase 4 BYOND trial, patients with pretreated chronic myeloid leukemia (CML) received bosutinib (starting dose: 500 mg/day). Efficacy and safety after ≥3 years of follow-up in 156 patients with Philadelphia chromosome-positive chronic phase CML by age and Charlson Comorbidity Index scores (without the age component; mCCI) is reported. Cumulative major molecular response rates at any time on treatment were 73.6%, 64.5%, and 74.1% in patients <65, 65-74, and ≥75 years of age, and 77.9%, 63.0%, and 59.3% in patients with mCCI scores 2, 3, and ≥4, respectively. Patients <65, 65-74, and ≥75 years of age experienced grade 3/4 treatment-emergent adverse events (TEAEs) at rates of 74.7%, 78.8%, and 96.4% and permanent discontinuations due to AEs at rates of 22.1%, 39.4%, and 46.4%, respectively. In patients with mCCI 2, 3, and ≥4, respective rates of grade 3/4 TEAEs were 77.8%, 77.8%, and 86.7%, and permanent discontinuations due to AEs were 25.3%, 33.3%, and 43.3%. In conclusion, a substantial proportion of patients maintained/achieved cytogenetic and molecular responses across age groups and mCCI scores. Older patients (≥75 years) and those with high comorbidity burden (mCCI ≥4) may require more careful monitoring due to the increased risk of TEAEs. Clinicaltrials.gov: NCT02228382.

Clinical Outcomes of Patients with Chronic Neuropathic Form of Gaucher Disease in the Spanish Real-World Setting: A Retrospective Study.

This was a retrospective, multicenter study that aimed to report the characteristics of type 3 Gaucher disease (GD3) patients in Spain, including the genotype, phenotype, therapeutic options, and treatment responses. A total of 19 patients with GD3 from 10 Spanish hospitals were enrolled in the study (14 men, 5 women). The median age at disease onset and diagnosis was 1 and 1.2 years, respectively, and the mean age at follow-up completion was 12.37 years (range: 1-25 years). Most patients exhibited splenomegaly (18/19) and hepatomegaly (17/19) at the time of diagnosis. The most frequent neurological abnormalities at onset were psychomotor retardation (14/19) and extrinsic muscle disorders (11/19), including oculomotor apraxia, supranuclear palsy, and strabismus. The L444P (c.1448T>C) allele was predominant, with the L444P (c.1448T>C) homozygous genotype mainly associated with visceral manifestations like hepatosplenomegaly, anemia, and thrombocytopenia. All patients received enzyme replacement therapy (ERT); other treatments included miglustat and the chaperone (ambroxol). Visceral manifestations, including hepatosplenomegaly and hematological and bone manifestations, were mostly controlled with ERT, except for kyphosis. The data from this study may help to increase the evidence base on this rare disease and contribute to improving the clinical management of GD3 patients.

Bosutinib for pretreated patients with chronic phase chronic myeloid leukemia: primary results of the phase 4 BYOND study.

Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of cumulative confirmed major cytogenetic response (MCyR) rate by 1 year was 75.8% in Ph+ CP CML patients after one or two prior TKIs and 62.2% after three prior TKIs. Cumulative complete cytogenetic response (CCyR) and major molecular response (MMR) rates by 1 year were 80.6% and 70.5%, respectively, in Ph+ CP CML patients overall. No patient progressed to AP/BP on treatment. Across all patients, the most common treatment-emergent adverse events were diarrhea (87.7%), nausea (39.9%), and vomiting (32.5%). The majority of patients had confirmed MCyR by 1 year and MMR by 1 year, further supporting bosutinib use for Ph+ CP CML patients resistant/intolerant to prior TKIs.

Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide.

We compared the health-related quality-of-life of patients with newly diagnosed multiple myeloma aged over 65 years or transplant-ineligible in the pivotal, phase III FIRST trial. Patients received: i) continuous lenalidomide and low-dose dexamethasone until disease progression; ii) fixed cycles of lenalidomide and low-dose dexamethasone for 18 months; or iii) fixed cycles of melphalan, prednisone, thalidomide for 18 months. Data were collected using the validated questionnaires (QLQ-MY20, QLQ-C30, and EQ-5D). The analysis focused on the EQ-5D utility value and six domains pre-selected for their perceived clinical relevance. Lenalidomide and low-dose dexamethasone, and melphalan, prednisone, thalidomide improved patients' health-related quality-of-life from baseline over the duration of the study across all pre-selected domains of the QLQ-C30 and EQ-5D. In the QLQ-MY20, lenalidomide and low-dose dexamethasone demonstrated a significantly greater reduction in the Disease Symptoms domain compared with melphalan, prednisone, thalidomide at Month 3, and significantly lower scores for QLQ-MY20 Side Effects of Treatment at all post-baseline assessments except Month 18. Linear mixed-model repeated-measures analyses confirmed the results observed in the cross-sectional analysis. Continuous lenalidomide and low-dose dexamethasone delays disease progression versus melphalan, prednisone, thalidomide and has been associated with a clinically meaningful improvement in health-related quality-of-life. These results further establish continuous lenalidomide and low-dose dexamethasone as a new standard of care for initial therapy of myeloma by demonstrating superior health-related quality-of-life during treatment, compared with melphalan, prednisone, thalidomide.

Guía de consenso nacionales para el estudio y tratamiento de los pacientes con leucemia linfocítica crónica / National guidelines for the management of patients with chronic lymphocytic leukemia

La leucemia linfocítica crónica es el síndrome linfoproliferativo crónico más frecuente en nuestro país, existiendo una amplia heterogeneidad en su abordaje clínico. En la actualidad, en España no se dispone de guías de consenso nacionales similares a las publicadas en otros países para su diagnóstico, clasificación pronóstica y tratamiento. El presente trabajo revisa la evidencia científica actual y aborda cuestiones relacionadas con el diagnóstico, el estudio de extensión, la presencia de comorbilidades y la clasificación de escalas pronósticas, los esquemas de tratamiento habituales estratificados por grupos de riesgo, el tratamiento de las complicaciones asociadas tanto a la enfermedad como a los procedimientos, así como diferentes controversias que rodean a la enfermedad y su tratamiento. El documento, realizado con la colaboración de expertos nacionales, permite establecer unas recomendaciones de carácter práctico, con su correspondiente nivel de evidencia y grado de recomendación, que facilitarán el diagnóstico, tratamiento y seguimiento de los pacientes con leucemia linfocítica crónica (AU)

Chronic lymphocytic leukemia is the most common chronic lymphoproliferative disorder in Spain. The clinical management of this entity varies widely. Currently, in Spain, there are no national consensus guidelines, such as those published in other countries, to guide the diagnosis and treatment of this malignancy and the use of prognostic scores. This article reviews the current scientific literature and addresses issues on the diagnosis of chronic lymphocytic leukemia, the spread of the disease, the presence of comorbidities, the classification of prognostic scores, the common treatment regimens stratified by risk factors, and the management of complications associated with both the disease and its treatment, as well as the various controversies related to this entity. This document was drafted with the collaboration of national experts and aims to establish practical guidelines with their corresponding levels of evidence and grades of recommendation to guide the diagnosis, treatment and follow-up of patients with chronic lymphocytic leukemia (AU)

[National guidelines for the management of patients with chronic lymphocytic leukemia. Sociedad Espan˜ola de Hematologi´a y Hemoterapia and Grupo Espan˜ol de Leucemia Linfoci´tica Cro´ nica]. / Guía de consenso nacionales para el estudio y tratamiento de los pacientes con leucemia linfocítica crónica. Sociedad Espan˜ola de Hematologi´a y Hemoterapia y por el Grupo Espan˜ol de Leucemia Linfoci´tica Cro´ nica.

Chronic lymphocytic leukemia is the most common chronic lymphoproliferative disorder in Spain. The clinical management of this entity varies widely. Currently, in Spain, there are no national consensus guidelines, such as those published in other countries, to guide the diagnosis and treatment of this malignancy and the use of prognostic scores. This article reviews the current scientific literature and addresses issues on the diagnosis of chronic lymphocytic leukemia, the spread of the disease, the presence of comorbidities, the classification of prognostic scores, the common treatment regimens stratified by risk factors, and the management of complications associated with both the disease and its treatment, as well as the various controversies related to this entity. This document was drafted with the collaboration of national experts and aims to establish practical guidelines with their corresponding levels of evidence and grades of recommendation to guide the diagnosis, treatment and follow-up of patients with chronic lymphocytic leukemia.

La afectación neurológica en la enfermedad de Gaucher

Libro que aborda todos los aspectos de la afectación neurológica en la enfermedad de Gaucher, desde su epidemiología hasta la disfunción mitocondrial, los genes implicados, el valor de los biomarcadores, las implicaciones del sistema inmune, el uso de la neuroimagen funcional o el tratamiento de la enfermedad, entre muchos otros temas.

Artritis erosiva seronegativa asociada a gammapatía monoclonal / Erosive seronegative arthritis associated with monoclonal gammopathy

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Tratamiento domiciliario de la enfermedad de Gaucher tipo 1 en España / Home therapy for type 1 Gaucher disease in Spain

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Transforming growth factor ß (TGF-ß) en la enfermedad de Gaucher. Resultados preliminares en un grupo de enfermos y familiares portadores y no portadores / Transforming growth factor ß (TGF-ß) in Gaucher's disease. Preliminary results in a group of patients and their relatives (carriers and non-carriers)

Fundamento: La escasa correlación fenotipo/genotipo en la enfermedad de Gaucher dificulta el tratamiento y la prevención de complicaciones. La fibrosis es precoz y condiciona buena parte del fenotipo. La citocina clave reguladora de la cicatrización y la fibrosis es el transforming growh factor ß (TGF-ß1). El objetivo de este trabajo es cuantificar los valores de TGF-ß1 plasmáticos en pacientes y portadores de enfermedad de Gaucher y en sujetos sanos no portadores y analizar si existe, en los pacientes, correlación entre el TGF-ß1 y el fenotipo expresado. Pacientes y método: Se determinaron los valores de TGF-ß1 plasmático en 11 pacientes, 12 portadores y 10 sujetos sanos. De los pacientes se recogieron, además, el tamaño del hígado y el bazo, la afectación esquelética, la cifra de hemoglobina, los recuentos leucocitario y plaquetario y el índice de gravedad de Zimran. Se determinaron las concentraciones de TGF-ß1 por radioinmunoanálisis, técnica de anticuerpos en sándwich y cuantificación por colorimetría. La sensibilidad fue de 25 pg/ml y la especificidad en cuanto a la reactividad cruzada fue < 5 por ciento con TGF-ß2 y TGF-ß3. El método estadístico empleado fue el test de ANOVA para la comparación de medias y el test de la t de Student para las comparaciones entre subgrupos de pacientes, ambos para muestras no apareadas. Resultados: El TGF-ß1 plasmático está significativamente elevado en los pacientes con enfermedad de Gaucher (98,4 [91,5] pg/ml), en comparación con los portadores (47,2 [21,7] pg/ml; p = 0,04), o sanos (40,8 [9,8] pg/ml; p = 0,02). En los pacientes con dicha enfermedad no se encontró correlación entre la concentración de TGF-ß1 y el índice de gravedad de Zimran o la afección esquelética. Conclusiones: En este grupo de pacientes con enfermedad de Gaucher, los valores plasmáticos de TGF-ß1 se encuentran elevados. No parece existir relación entre sus valores y la expresión fenotípica, por lo que podría tratarse de un marcador de activación macrofágica. (AU)

Tratamiento de la enfermedad de Gaucher tipo 1. Mucho camino aún por recorrer / Gaucher's disease therapy. Still a long way to go over

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