chlorambucil
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Tratamiento de enfermedad de Hodgkin, determinadas formas de linfoma no Hodgkin, leucemia linfocítica crónica y macroglobulinemia de Waldenström.
Contraindicaciones
Absolutas
- Hipersensibilidad y uso para enfermedades no malignas.
Advertencias clínicas
- Realiza hemogramas frecuentes durante el tratamiento oral; aplaza o modifica ante mielosupresión. La supresión puede ser irreversible y causar infección o hemorragia grave. — CIMA/AEMPS, ficha técnica 85506
- Puede causar convulsiones, hepatotoxicidad, SCAR, mutagenicidad, infertilidad y neoplasias hematológicas secundarias. — CIMA/AEMPS, ficha técnica 85506
Interacciones medicamentosas
- SeveraVacunas vivas
Mecanismo: La inmunosupresión puede producir una infección vacunal diseminada.
Recomendación: No se recomiendan durante la inmunosupresión; planifica la vacunación con el equipo tratante.
CIMA/AEMPS, ficha técnica 85506
- SeveraAnálogos de purina
Mecanismo: Pueden aumentar la toxicidad hematológica.
Recomendación: Evita o intensifica el control hematológico según el protocolo.
CIMA/AEMPS, ficha técnica 85506
- SeveraFenilbutazona
Mecanismo: Puede aumentar la toxicidad de clorambucilo.
Recomendación: Vigila toxicidad y considera reducir la dosis de clorambucilo.
CIMA/AEMPS, ficha técnica 85506
Eventos adversos
Comunes (≥1%)
Leucopenia, neutropenia, trombocitopenia, anemia, náuseas y vómitos
Embarazo y lactancia
Evita clorambucilo durante el embarazo, especialmente en el primer trimestre, salvo que sea absolutamente esencial. Usa anticoncepción adecuada mientras cualquiera de los miembros de la pareja recibe tratamiento. No amamantes. Puede causar amenorrea o azoospermia.
Bibliografía reciente (PubMed)
In the CLL14 study, patients with previously untreated chronic lymphocytic leukemia (CLL) and coexisting conditions were randomized to 12 cycles of venetoclax-obinutuzumab (Ven-Obi, n = 216) or chlorambucil-obinutuzumab (Clb-Obi, n = 216). Progression-free survival (PFS) was the primary end point. Key secondary end points included time-to-next-treatment (TTNT), rates of undetectable minimal residual disease (uMRD), overall survival (OS), and rates of adverse events. Patient reported outcomes of time until definitive deterioration (TUDD) in quality of life (QoL) were analyzed. At a median observation time of 76.4 months, PFS remained superior for Ven-Obi compared with Clb-Obi (median, 76.2 vs 36.4 months; hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.31-0.52; P < .0001). Likewise, TTNT was longer after Ven-Obi (6-year TTNT, 65.2% vs 37.1%; HR, 0.44; 95% CI, 0.33-0.58; P < .0001). In the Ven-Obi arm, presence of del(17p), unmutated immunoglobulin heavy-chain variable region, and lymph node size of ≥5 cm were independent prognostic factors for shorter PFS. The 6-year OS rate was 78.7% in the Ven-Obi and 69.2% in the Clb-Obi arm (HR, 0.69; 95% CI, 0.48-1.01; P = .052). A significantly longer TUDD in global health status/QoL was observed in the Ven-Obi than in the Clb-Obi arm (median, 82.1 vs 65.1 months; HR, 0.70; 95% CI, 0.51-0.97). Follow-up-adjusted second primary malignancies incidence rates were 2.3 and 1.4 per 1000 patient-months in the Ven-Obi and Clb-Obi arm, respectively. The sustained long-term survival and QoL benefits support the use of 1-year fixed-duration Ven-Obi in CLL. This trial was registered at www.ClinicalTrials.gov as #NCT02242942.
Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia. We present results from ELEVATE-TN after a median follow-up of 74.5 months. Overall, 535 patients were randomized (acalabrutinib-obinutuzumab, n = 179; acalabrutinib, n = 179; chlorambucil-obinutuzumab, n = 177). Median age was 70 years, 63.0% had unmutated immunoglobulin heavy chain variable region gene (uIGHV), 13.6% had del(17p) and/or mutated TP53, and 17% had complex karyotype (CK; ≥3 chromosomal abnormalities). Median progression-free survival (PFS) was not reached (NR) for acalabrutinib-obinutuzumab and acalabrutinib vs 27.8 months for chlorambucil-obinutuzumab (both P < .0001); estimated 72-month overall PFS rates were 78.0%, 61.5%, and 17.2%, respectively. Acalabrutinib-obinutuzumab resulted in improved PFS vs acalabrutinib monotherapy (hazard ratio [HR], 0.58; P = .0229). Patients with uIGHV, del(17p) and/or mutated TP53, or CK had significantly improved PFS with acalabrutinib ± obinutuzumab vs chlorambucil-obinutuzumab (P < .0001, P ≤ .0009, and P < .0001 for both acalabrutinib-containing arms, respectively). Median overall survival (OS) was NR for all treatments, with significantly longer OS for acalabrutinib-obinutuzumab than chlorambucil-obinutuzumab (HR, 0.62; P = .0349). Estimated 72-month OS rates were 83.9%, 75.5%, and 74.7% for acalabrutinib-obinutuzumab, acalabrutinib, and chlorambucil-obinutuzumab, respectively. Adverse events (AEs) occurring after >4 years were mostly grade 1 to 2. Rates of AEs, serious AEs, and events of clinical interest were similar between acalabrutinib-containing arms and consistent with the known safety profiles of acalabrutinib and obinutuzumab. Efficacy and safety of acalabrutinib-containing arms were maintained, with longer PFS in both acalabrutinib arms than chlorambucil-obinutuzumab including in patients with high-risk features. This trial was registered at www.ClinicalTrials.gov as #NCT02475681. No informa
In the GLOW study, fixed-duration ibrutinib-venetoclax showed superior progression-free survival versus chlorambucil-obinutuzumab in patients with previously untreated chronic lymphocytic leukaemia who were older or had comorbidities, or both, at a median follow up of 27·7 months. In this Article, we report updated outcomes from GLOW after a 46-month median follow-up. GLOW was a randomised, multicentre, phase 3 study done at 67 hospital centres across 14 countries. Patients aged 65 years and older or 18-64 years with previously untreated chronic lymphocytic leukaemia and a cumulative illness rating scale score of more than 6 or creatinine clearance less than 70 mL/min, or both, and an Eastern Cooperative Oncology Group performance status of 2 or less were randomly assigned (1:1) via an interactive web system with permuted blocks (block size of four) and stratified by IGHV mutational status and the presence of del11q aberration to the ibrutinib-venetoclax group (three cycles of ibrutinib lead-in [420 mg/day, orally], followed by 12 cycles of ibrutinib plus venetoclax [400 mg/day, orally, including a 5-week dose ramp-up]) or the chlorambucil-obinutuzumab group (six cycles of chlorambucil [0·5 mg/kg, orally, on days 1 and 15 of each cycle], and obinutuzumab [1000 mg, intravenously, on days 1 (or 100 mg on day 1 and 900 mg on day 2), 8, and 15 of cycle 1 and day 1 of cycles 2-6]). The primary endpoint was progression-free survival in the intention-to-treat population, assessed by an independent review committee. The safety population included all randomised patients who received at least one dose of the study treatment. This study is registered with ClinicalTrials.gov (NCT03462719) and the EU Clinical Trials Register (EudraCT 2017-004699-77). Between May 4, 2018, and April 5, 2019, 211 patients (122 [58%] were male and 89 [42%] were female) were randomly assigned to receive ibrutinib-venetoclax (n=106) or chlorambucil-obinutuzumab (n=105). At a median of 46 months (IQR
- Fixed-Duration Ibrutinib-Venetoclax in Patients with Chronic Lymphocytic Leukemia and Comorbidities.
BACKGROUND: GLOW is a phase 3 trial evaluating the efficacy and safety of ibrutinib-venetoclax in older patients and/or those with comorbidities with previously untreated chronic lymphocytic leukemia (CLL). METHODS: We randomly assigned (1:1) patients 65 years of age or older or those 18 to 64 years of age who also had a Cumulative Illness Rating Scale (CIRS) score greater than 6 (CIRS scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or creatinine clearance of less than 70 ml/min, to ibrutinib-venetoclax (3 cycles ibrutinib lead-in, then 12 cycles ibrutinib-venetoclax) or chlorambucil-obinutuzumab (6 cycles). The primary end point was progression-free survival (PFS) assessed by an independent review committee. Secondary end points included undetectable minimal residual disease (uMRD), response rates, and safety. RESULTS: This study enrolled 211 patients, with 106 randomly assigned to ibrutinib-venetoclax and 105 to chlorambucil-obinutuzumab. With a median follow-up of 27.7 months, there were 22 PFS events for ibrutinib-venetoclax and 67 events for chlorambucil-obinutuzumab. PFS was significantly longer for ibrutinib-venetoclax than for chlorambucil-obinutuzumab (hazard ratio, 0.216; 95% confidence interval [CI], 0.131 to 0.357; P<0.001). The improvement in PFS with ibrutinib-venetoclax was consistent across predefined subgroups, including patients 65 years of age or older or with a CIRS score greater than 6. The best uMRD rate in bone marrow by next-generation sequencing was significantly higher for ibrutinib-venetoclax (55.7%) than for chlorambucil-obinutuzumab (21.0%; P<0.001). The proportion of patients with sustained uMRD in peripheral blood from 3 to 12 months after end of treatment was 84.5% for ibrutinib-venetoclax and 29.3% for chlorambucil-obinutuzumab. Four patients treated with ibrutinib-venetoclax required subsequent therapy compared with 27 patients receiving chlorambucil-obinutuzumab (hazard ratio, 0.143