RESUMO
Richter syndrome (RS) is an uncommon evolution of chronic lymphocytic leukaemia (CLL) with a dismal prognosis. Clinical-biological features predicting outcome and best therapeutic approach for these patients remain to be established. In this study, 128 patients with RS, including 112 diffuse large B-cell lymphoma (DLBCL)-type RS, 15 Hodgkin lymphoma (HL)-type RS, and one plasmablastic lymphoma, were identified in 11 centres of the Spanish CLL Study Group (GELLC). The median overall survival (OS) was 5·9 months for DLBCL-type RS and 30·8 months for HL-type RS. Eastern Cooperative Oncology Group Performance Status, haemoglobin level, platelet count, serum lactate dehydrogenase and ß2-microglobulin levels, tumour protein p53 (TP53) abnormalities in the CLL clone concomitant to RS, number of prior therapies, and clonal relationship between CLL and RS, were associated with OS in patients with DLBCL-type RS. A platelet count of <100 × 109 /l, prior CLL therapy (0 vs. ≥1), and presence of TP53 alterations maintained an independent prognostic impact in the multivariate analysis. Patients without any of these factors had a better clinical outcome, with a median OS of 75·3 months, while patients with one or two or more of these factors presented a median OS of 25·5 and 3 months, respectively. Although OS of patients with RS is generally poor, a proportion of patients achieved prolonged survival. Treatment of RS remains a medical need, and further therapeutic approaches with novel therapies are warranted.
Assuntos
Doença de Hodgkin , Leucemia Linfocítica Crônica de Células B , Linfoma Difuso de Grandes Células B , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Doença de Hodgkin/sangue , Doença de Hodgkin/genética , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/terapia , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Taxa de Sobrevida , SíndromeRESUMO
BACKGROUND: The efficacy of erythropoietic-stimulating agents (ESA) in chronic myelomonocytic leukemia (CMML) is unknown. Our objective was to analyze erythroid response (ER) and overall survival (OS) in a series of 94 patients with CMML treated with ESA. METHODS: We analyzed a series of 94 patients with CMML treated with ESA included in the Spanish and Düsseldorf-MDS registries. FINDINGS: ER was observed in 64% of patients and red blood cell (RBC) transfusion independence in 31%. The median duration of ER was 7 months (range, 0-88). CPSS and EPO level were significantly associated with ER in multivariate analysis (P = 0.003). Considering only patients with CPSS low- or intermediate-1-risk group, the absence of RBC transfusion dependence and erythropoietin (EPO) level predicted ER (P = 0.003 and P = 0.008, respectively). In multivariate analysis, only the EPO level retained its prognostic value (P = 0.029). Achievement of ER correlated with a better survival since ER evaluation (P = 0.016). INTERPRETATION: The CPSS and EPO levels are adequate tools to select CMML patients with symptomatic anemia who may benefit from treatment with ESA. A significant ER to ESA is expected in anemic patients with low/intermediate-1 CMML risk by the CPSS and a low endogenous serum EPO level.
Assuntos
Anemia/tratamento farmacológico , Anemia/etiologia , Hematínicos/uso terapêutico , Leucemia Mielomonocítica Crônica/complicações , Idoso , Idoso de 80 Anos ou mais , Anemia/diagnóstico , Anemia/mortalidade , Progressão da Doença , Feminino , Seguimentos , Hematínicos/administração & dosagem , Hematínicos/efeitos adversos , Humanos , Leucemia Mielomonocítica Crônica/diagnóstico , Leucemia Mielomonocítica Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do TratamentoRESUMO
Background: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work. Methods: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022. Findings: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs).The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79-4.91; p < 0.001). STs were more frequent in males and patients with unmutated immunoglobulin heavy variable genes (OR = 1.77; 95% CI = 1.49-2.11; p < 0.001/OR = 1.89; 95% CI = 1.6-2.24; p < 0.001).CLL-directed treatment was associated with non-melanoma skin and prostate cancers (OR = 1.8; 95% CI = 1.36-2.41; p < 0.001/OR = 2.11; 95% CI = 1.12-3.97; p = 0.021). In contrast, breast cancers were more frequent in untreated patients (OR = 0.17; 95% CI = 0.08-0.33; p < 0.001).Patients with CLL and an OM had inferior overall survival (OS) than those without. AML and MDS conferred the worst OS (p < 0.001). Interpretation: OMs in CLL impact on OS. Treatment for CLL increased the risk for AML/MDS, prostate cancer, and NMSC. FCR was associated with increased risk for AML/MDS. Funding: AbbVie, and EU/EFPIAInnovative Medicines Initiative Joint Undertaking HARMONY grant n° 116026.
RESUMO
OBJECTIVE: Chronic lymphocytic leukaemia places a considerable economic burden on the Spanish National Health System. This study estimated the direct costs of chronic lymphocytic leukaemia oral targeted therapies from 2011 to 2025, inclusive, in a scenario with fixed treatment oral targeted therapies and in a scenario without them. Method: The clinical course of adult chronic lymphocytic leukaemia patients was represented by a Markov model with four health states: watchful waiting, first-line treatment, relapse, and death. The treatment pattern was defined according to patient type by disease status or situation, age, presence or absence of deletion in the short arm of chromosome 17, immunoglobulin heavy chain mutation status, and year of treatment. The treatment algorithm was simulated from 2011 to 2025, and included therapies funded by the Spanish National Health System and their use in routine clinical practice, validated by leading experts. A single treatment option was assumed for each type of patient and time period (the most widely option used at each time point). Direct costs were included: pharmacological, administration, tests performed, routine visits, hospitalizations, and adverse events. Results: From 2011 to 2025, there would be a mean annual chronic ymphocytic leukaemia prevalence of 16,436 patients in the scenario without fixed treatment oral targeted therapies and 16,413 in the scenario with in the scenario without fixed treatment oral targeted therapies would be 4,676.7 million and in the scenario with fixed treatment oral targeted therapies they would be 4,111.8 million. Thus, the introduction of fixed treatment oral targeted therapies would entail a saving of 564.9 million (12.1% of the total cost of care of chronic lymphocytic leukaemia patients during the period assessed). In this period, the total cost per patient would decrease from 266,019 in the scenario without fixed treatment oral targeted therapies to 236,852 in the scenario with fixed treatment oral targeted therapies, representing a saving of 29,167 per patient. CONCLUSIONS: This study estimates that, between 2011 and 2025, the introduction of fixed treatment oral targeted therapies for the treatment of chronic lymphocytic leukaemia would entail 564.9 million cost savings for the Spanish National Health System (12.1% of the total cost of care of chronic lymphocytic leukaemia patients during the period assessed).
OBJETIVO: La leucemia linfocítica crónica supone una carga económica considerable para el Sistema Nacional de Salud español. Este estudio estimó los costes directos de las terapias orales dirigidas para leucemia linfocítica crónica desde 2011 a 2025, inclusive, en un escenario con terapias orales de duración fija y en un escenario sin ellas.Método: Se representó el curso clínico de pacientes adultos con leucemia linfocítica crónica mediante un modelo de Markov con cuatro estados de salud: vigilancia activa, tratamiento de primera línea, recaída y muerte. Patrón de tratamiento definido por tipo de paciente: estado o situación de la enfermedad, edad, presencia o no de deleción en el brazo corto del cromosoma 17, estado mutacional de la cadena pesada de inmunoglobulinas y año de tratamiento. Algoritmo de tratamiento simulado desde 2011 a 2025, incluyendo terapias financiadas por el Sistema Nacional de Salud español y su uso en práctica clínica habitual, validado por expertos de referencia. Se asumió una opción de tratamiento por tipo de paciente y periodo de tiempo (la más ampliamente utilizada en cada momento). Se incluyeron costes directos: farmacológicos, administración, pruebas realizadas, visitas rutinarias, hospitalizaciones y acontecimientos adversos. RESULTADOS: Se estimó una prevalencia media anual de leucemia linfocítica crónica desde 2011 a 2025 de 16.436 pacientes en el escenario sin terapias orales de duración fija y 16.413 en el escenario con terapias orales de duración fija. Los costes totales desde 2011 a 2025 en el escenario sin terapias orales de duración fija ascendieron a 4.676,7 millones de y a 4.111,8 millones de en el escenario con terapias orales de duración fija. Así, la introducción de las terapias orales de duración fija supondría un ahorro de 564,9 millones de (12,1% del total del coste de atención de los pacientes con leucemia linfocítica crónica durante el periodo evaluado). El coste total por paciente en este periodo de tiempo pasaba de 266.019 en el escenario sin terapias orales de duración fija a 236.852 en el escenario con terapias rales de duración fija, suponiendo un ahorro de 29.167 por paciente. CONCLUSIONES: Este estudio estima que la introducción de las terapias orales de duración fija para el tratamiento de la leucemia linfocítica crónica entre 2011 y 2025 supone un ahorro para el Sistema Nacional de Salud español de 564,9 millones de (12,1% del total del coste de atención de los pacientes con leucemia linfocítica crónica durante el periodo evaluado).
Assuntos
Leucemia Linfocítica Crônica de Células B , Administração Oral , Adulto , Custos e Análise de Custo , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , EspanhaRESUMO
Up to 25% of patients with classical Hodgkin lymphoma (cHL) and a negative interim PET/CT will progress. Unfortunately, there are few published studies on the predictive value of PET/CT performed after finishing treatment. The objective of our study was to assess the role of the final PET/CT (fPET/CT) in predicting progression in a retrospective series of patients treated in the last 10 years with a homogeneous protocol (ABVD + / - radiotherapy). We reviewed a cohort of 227 patients with newly diagnosed cHL. fPET/CT was performed on 212 patients (93%). In patients with a positive fPET, progression-free survival at 60 months was 17% (94% if fPET was negative, p = 0.000). The positive and negative predictive values for the fPET were 76% and 94%, respectively (Fisher's exact test, p = 0.000). In the subgroup of patients with advanced-stage cHL, progression-free survival at 60 months was 91% with negative fPET and 0% with positive fPET (p = 0.000). However, fPET was negative in 19 of the 29 patients with a positive interim PET/CT (only 2 showed progression). In conclusion, fPET is a useful tool to predict treatment failure in patients with newly diagnosed cHL, especially advanced-stage disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxa de Sobrevida , Falha de Tratamento , Vimblastina/administração & dosagem , Adulto JovemRESUMO
BACKGROUND: Ibrutinib demonstrated remarkable efficacy and favorable tolerability in patients with untreated or relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), including those with high-risk genetic alterations. The IBRORS-CLL study assessed the characteristics, clinical management and outcome of CLL patients receiving ibrutinib in routine clinical practice in Spain. PATIENTS: Observational, retrospective, multicenter study in CLL patients who started single-agent ibrutinib as first-line treatment or at first or second relapse between January 2016 and January 2019. RESULTS: A total of 269 patients were included (median age: 70.9 years; cardiovascular comorbidity: 55.4%, including hypertension [47.6%] and atrial fibrillation [AF] [7.1%]). Overall, 96.7% and 69% of patients underwent molecular testing for del(17p)/TP53 mutation and IGHV mutation status. High-risk genetic features included unmutated IGHV (79%) and del(17p)/TP53 mutation (first-line: 66.3%; second-line: 23.1%). Overall, 84 (31.2%) patients received ibrutinib as first-line treatment, and it was used as second- and third-line therapy in 121 (45.0%) and 64 (23.8%) patients. The median progression-free survival and overall survival were not reached irrespective of del(17p)/TP53, or unmutated IGHV. Common grade ≥3 adverse events were infections (12.2%) and bleeding (3%). Grade ≥3 AF occurred in 1.5% of patients. CONCLUSION: This real-world study shows that single-agent ibrutinib is an effective therapy for CLL, regardless of age and high-risk molecular features, consistent with clinical trials. Additionally, single-agent ibrutinib was well tolerated, with a low rate of cardiovascular events. This study also emphasized a high molecular testing rate of del(17p)/TP53 mutation and IGHV mutation status in clinical practice according to guideline recommendations.
Assuntos
Leucemia Linfocítica Crônica de Células B , Adenina/análogos & derivados , Idoso , Humanos , Piperidinas , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
We investigated the effectiveness and tolerability of azacitidine in patients with World Health Organization-defined myelodysplastic syndromes, or acute myeloid leukemia with 20-30% bone marrow blasts. Patients were treated with azacitidine, with one of three dosage regimens: for 5 days (AZA 5); 7 days including a 2-day break (AZA 5-2-2); or 7 days (AZA 7); all 28-day cycles. Overall response rates were 39.4%, 67.9%, and 51.3%, respectively, and median overall survival (OS) durations were 13.2, 19.1, and 14.9 months. Neutropenia was the most common grade 3-4 adverse event. These results suggest better effectiveness-tolerability profiles for 7-day schedules.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Azacitidina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Azacitidina/efeitos adversos , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
Bendamustine is a alkylating agent with a purine-like benzamidazole ring currently approved in Europe for indolent non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma. Our aim was to analyze retrospectively the efficacy and toxicity of bendamustine in NHL and CLL in Spain in the bendamustine Compassionate Use Program. Patients with relapsed/refractory NHL or CLL were eligible. Any regimen containing bendamustine was eligible. 109 patients were included from 22 institutions. Forty-nine patients had indolent NHL, 18 aggressive NHL and 42 CLL, being 44 patients (40%) refractory to previous treatment. 63% of patients had adverse events grade 3-4, mainly hematological. Overall response rate (ORR) was 66%, complete responses 30%. ORR observed in refractory patients was 45%. The median progression-free survival (PFS) was 13 months. Outcome was influenced by histology, number of previous treatments, resistance to previous chemotherapy and type of response achieved with bendamustine. Alone or in combination, bendamustine shows a meaningful clinical antitumor activity in patients with relapsed or refractory NHL or CLL, with an acceptable toxicity profile.