EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia.

On November 5, 2020, a marketing authorization valid through the European Union (EU) was issued for acalabrutinib monotherapy or acalabrutinib in combination with obinutuzumab (AcalaObi) in adult patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) and also for acalabrutinib monotherapy in adult patients with relapsed or refractory (RR) CLL. Acalabrutinib inhibits the Bruton tyrosine kinase, which plays a significant role in the proliferation and survival of the disease. Acalabrutinib was evaluated in two phase III multicenter randomized trials. The first trial (ACE-CL-007) randomly allocated acalabrutinib versus AcalaObi versus chlorambucil plus obinutuzumab (ChlObi) to elderly/unfit patients with TN CLL. The progression-free survival (PFS), as assessed by an independent review committee, was superior for both the AcalaObi (hazard ratio [HR], 0.1; 95% confidence interval [CI], 0.06-0.17) and acalabrutinib (HR, 0.2; 95% CI, 0.13-0.3) arms compared with the ChlObi arm. The second trial (ACE-CL-309) randomly allocated acalabrutinib versus rituximab plus idelalisib or bendamustine to adult patients with RR CLL. Also in this trial, the PFS was significantly longer in the acalabrutinib arm (HR, 0.31; 95% CI, 0.20-0.49). Adverse events for patients receiving acalabrutinib varied across trials, but the most frequent were generally headache, diarrhea, neutropenia, nausea, and infections. The scientific review concluded that the benefit-risk ratio of acalabrutinib was positive for both indications. This article summarizes the scientific review of the application leading to regulatory approval in the EU. IMPLICATIONS FOR PRACTICE: Acalabrutinib was approved in the European Union for the treatment of adult patients with chronic lymphocytic leukemia who have not received treatment before and for those who have received therapy but whose disease did not respond or relapsed afterward. Acalabrutinib resulted in a clinically meaningful and significant lengthening of the time from treatment initiation to further disease relapse or patient's death compared with standard therapy. The overall safety profile was considered acceptable, and the benefit-risk ratio was determined to be positive.

Long-term changes in the quality of life of patients with rheumatoid arthritis treated with biological therapies. / Evolución a largo plazo de la calidad de vida en pacientes con artritis reumatoide tratados con terapias biológicas.

OBJECTIVE: To analyze the changes in health-related quality of life (HRQoL) of patients with rheumatoid arthritis (RA) treated with biological therapies. METHOD: Observational prospective study performed from October 2006 to May 2011. The inclusion criteria were adult patients, diagnosed with RA, treated for at least one year with anti-tumor necrosis factor therapy (infliximab or etanercept), who had not received other biological treatments previously. A total of 41 patients who completed the study undertook the specific and validated questionnaire QoL-RA Scale 3 times: E1 (September 2006-February 2007), E2 (April 2008-January 2009) and E3 (July 2010- May 2011). Data analysis was conducted using Epi-Info version 3.3 2004 for Windows® and Excel 2007; mean comparisons were evaluated by Student's t-test and the relationship between the 3 outcomes for each patient by lineal regression. RESULTS: Overall results show a downward trend which was not statistically significant: 7.09 (standard deviation [SD]=1.15) in E1; 6.90 (SD=1.60) in E2; and 6.52 (SD=1.59) in E3. Items with higher scores were those related to psychosocial aspects (help from family, interaction with family and friends), whereas the physical dimension was valued more poorly (physical ability, arthritis pain, arthritis). Between E2 and E3 there was a significant increase in help from family (P=.0008), whereas level of tension (P=.0119) and mood (P=.0451) decreased significantly. CONCLUSIONS: In all, HRQoL reported by patients is good and has remained unchanged after approximately 6 years of study. The stability of HRQoL is probably partly attributable to treatment.

Evolución a largo plazo de la calidad de vida en pacientes con artritis reumatoide tratados con terapias biológicas / Long-term changes in the quality of life of patients with rheumatoid arthritis treated with biological therapies

Objetivo: Analizar la evolución a largo plazo de la calidad de vida relacionada con la salud (CVRS) en pacientes con artritis reumatoide (AR) tratados con terapias biológicas. Método: Estudio observacional prospectivo realizado entre octubre de 2006 y mayo de 2011. Se seleccionó a pacientes mayores de edad, diagnosticados de AR, tratados durante al menos un año con anti-TNF (infliximab o etanercept) y que no hubieran recibido otros tratamientos biológicos previos. Completaron el estudio 41 pacientes, cumplimentando el cuestionario específico validado QOL-AR en 3ocasiones: E1 (entre septiembre de 2006 y febrero de 2007), E2 (entre abril de 2008 y enero de 2009) y E3 (entre julio de 2010 y mayo de 2011). Los datos se analizaron con Epi-Info versión 3.3-2004 para Windows (R) y Excel 2007; la comparación de las medias con la prueba t de Student y la relación entre valores de un mismo paciente, mediante regresión lineal. Resultados: Resultados globales: tendencia descendente no estadísticamente significativa: 7,09±1,15 en E1; 6,90±1,60 en E2 y 6,52±1,59 en E3. Los ítems con mayor puntuación fueron los relacionados con aspectos psicosociales (ayuda familiar, interacción con familia y amigos). La dimensión física fue la peor valorada (habilidad física, dolor artrítico, artritis). Entre E2 y E3 aumentó significativamente la valoración de la ayuda familiar (p=0,0008) y disminuyeron significativamente tensión nerviosa (p=0,0119) y estado de ánimo (p=0,0451). Conclusiones: La CVRS de los pacientes es buena y se ha mantenido prácticamente invariable tras unos 6años de estudio. Es probable que parte de la estabilidad en la CVRS sea atribuible al tratamiento

Objective: To analyze the changes in health-related quality of life (HRQoL) of patients with rheumatoid arthritis (RA) treated with biological therapies. Method: Observational prospective study performed from October 2006 to May 2011. The inclusion criteria were adult patients, diagnosed with RA, treated for at least one year with anti-tumor necrosis factor therapy (infliximab or etanercept), who had not received other biological treatments previously. A total of 41 patients who completed the study undertook the specific and validated questionnaire QoL-RA Scale 3 times: E1 (September 2006-February 2007), E2 (April 2008-January 2009) and E3 (July 2010- May 2011). Data analysis was conducted using Epi-Info version 3.3 2004 for Windows(R) and Excel 2007; mean comparisons were evaluated by Student's t-test and the relationship between the 3 outcomes for each patient by lineal regression. Results: Overall results show a downward trend which was not statistically significant: 7.09 (standard deviation [SD]=1.15) in E1; 6.90 (SD=1.60) in E2; and 6.52 (SD=1.59) in E3. Items with higher scores were those related to psychosocial aspects (help from family, interaction with family and friends), whereas the physical dimension was valued more poorly (physical ability, arthritis pain, arthritis). Between E2 and E3 there was a significant increase in help from family (P=.0008), whereas level of tension (P=.0119) and mood (P=.0451) decreased significantly. Conclusions: In all, HRQoL reported by patients is good and has remained unchanged after approximately 6 years of study. The stability of HRQoL is probably partly attributable to treatment