Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
1.
Lancet Oncol ; 23(8): 1031-1043, 2022 08.
Article in English | MEDLINE | ID: covidwho-1926992

ABSTRACT

BACKGROUND: Zanubrutinib is a next-generation, selective Bruton tyrosine kinase inhibitor with efficacy in relapsed chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). We compared zanubrutinib with bendamustine-rituximab to determine its effectiveness as frontline therapy in patients with CLL or SLL. METHODS: We conducted an open-label, multicentre, phase 3 study at 153 academic or community hospitals in 14 countries and regions. Eligible patients had untreated CLL or SLL requiring treatment as per International Workshop on CLL criteria; were aged 65 years or older, or 18 years or older and had comorbidities; and had an Eastern Cooperative Oncology Group performance status score of 0-2. A central interactive web response system randomly assigned patients without del(17)(p13·1) to zanubrutinib (group A) or bendamustine-rituximab (group B) by sequential block method (permutated blocks with a random block size of four). Patients with del(17)(p13·1) were enrolled in group C and received zanubrutinib. Zanubrutinib was administered orally at 160 mg twice per day (28-day cycles); bendamustine at 90 mg/m2 of body surface area on days 1 and 2 for six cycles plus rituximab at 375 mg/m2 of body surface area the day before or on day 1 of cycle 1, and 500 mg/m2 of body surface area on day 1 of cycles 2-6, were administered intravenously. The primary endpoint was progression-free survival per independent review committee in the intention-to-treat population in groups A and B, with minimum two-sided α of 0·05 for superiority. Safety was analysed in all patients who received at least one dose of study treatment. The study is registered with ClinicalTrials.gov, NCT03336333, and is closed to recruitment. FINDINGS: Between Oct 31, 2017, and July 22, 2019, 590 patients were enrolled; patients without del(17)(p13·1) were randomly assigned to zanubrutinib (group A; n=241) or bendamustine-rituximab (group B; n=238). At median follow-up of 26·2 months (IQR 23·7-29·6), median progression-free survival per independent review committee was not reached in either group (group A 95% CI not estimable [NE] to NE; group B 28·1 months to NE). Progression-free survival was significantly improved in group A versus group B (HR 0·42 [95% CI 0·28 to 0·63]; two-sided p<0·0001). The most common grade 3 or worse adverse event was neutropenia (27 [11%] of 240 patients in group A, 116 [51%] of 227 in group B, and 17 [15%] of 111 patients in group C). Serious adverse events occurred in 88 (37%) of 240 patients in group A, 113 (50%) of 227 patients in group B, and 45 (41%) of 111 patients in group C. Adverse events leading to death occurred in 11 (5%) of 240 patients in group A, 12 (5%) of 227 patients in group B, and three (3%) of 111 patients in group C, most commonly due to COVID-19 (four [2%] of 240 patients in group A), diarrhoea, and aspiration pneumonia (two each [1%] of 227 patients in group B). INTERPRETATION: Zanubrutinib significantly improved progression-free survival versus bendamustine-rituximab, with an acceptable safety profile consistent with previous studies. These data support zanubrutinib as a potential new treatment option for untreated CLL and SLL. FUNDING: BeiGene.


Subject(s)
COVID-19 , Leukemia, Lymphocytic, Chronic, B-Cell , Sequoia , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bendamustine Hydrochloride , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Piperidines , Pyrazoles , Pyrimidines , Rituximab
2.
Leuk Lymphoma ; 62(12): 2820-2822, 2021 12.
Article in English | MEDLINE | ID: covidwho-1327279
3.
Leukemia ; 35(7): 1864-1872, 2021 07.
Article in English | MEDLINE | ID: covidwho-1216445

ABSTRACT

Standard treatment options in classic HCL (cHCL) result in high response rates and near normal life expectancy. However, the disease itself and the recommended standard treatment are associated with profound and prolonged immunosuppression, increasing susceptibility to infections and the risk for a severe course of COVID-19. The Hairy Cell Leukemia Foundation (HCLF) has recently convened experts and discussed different clinical strategies for the management of these patients. The new recommendations adapt the 2017 consensus for the diagnosis and management with cHCL to the current COVID-19 pandemic. They underline the option of active surveillance in patients with low but stable blood counts, consider the use of targeted and non-immunosuppressive agents as first-line treatment for cHCL, and give recommendations on preventive measures against COVID-19.


Subject(s)
COVID-19/complications , Leukemia, Hairy Cell/therapy , COVID-19/epidemiology , COVID-19/pathology , COVID-19/virology , Consensus , Humans , Leukemia, Hairy Cell/complications , Pandemics , Practice Guidelines as Topic , SARS-CoV-2/isolation & purification , Severity of Illness Index
4.
Intern Med J ; 50(6): 667-679, 2020 06.
Article in English | MEDLINE | ID: covidwho-271531

ABSTRACT

The COVID-19 pandemic poses a unique challenge to the care of patients with haematological malignancies. Viral pneumonia is known to cause disproportionately severe disease in patients with cancer, and patients with lymphoma, myeloma and chronic lymphocytic leukaemia are likely to be at particular risk of severe disease related to COVID-19. This statement has been developed by consensus among authors from Australia and New Zealand. We aim to provide supportive guidance to clinicians making individual patient decisions during the COVID-19 pandemic, in particular during periods that access to healthcare resources may be limited. General recommendations include those to minimise patient exposure to COVID-19, including the use of telehealth, avoidance of non-essential visits and minimisation of time spent by patients in infusion suites and other clinical areas. This statement also provides recommendations where appropriate in assessing indications for therapy, reducing therapy-associated immunosuppression and reducing healthcare utilisation in patients with specific haematological malignancies during the COVID-19 pandemic. Specific decisions regarding therapy of haematological malignancies will need to be individualised, based on disease risk, risks of immunosuppression, rates of community transmission of COVID-19 and available local healthcare resources.


Subject(s)
Consensus , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Infection Control/methods , Leukemia, Lymphocytic, Chronic, B-Cell/physiopathology , Lymphoma/physiopathology , Multiple Myeloma/physiopathology , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Australia , Betacoronavirus/immunology , COVID-19 , Comorbidity , Coronavirus Infections/immunology , Coronavirus Infections/virology , Drug Therapy , Guideline Adherence , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Lymphoma/immunology , Lymphoma/therapy , Multiple Myeloma/immunology , Multiple Myeloma/therapy , New Zealand , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Practice Guidelines as Topic , Risk Assessment , SARS-CoV-2 , Salvage Therapy/methods , Stem Cell Transplantation/methods
SELECTION OF CITATIONS
SEARCH DETAIL