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30 záznamů v Články Filtry

Článek

Pretreatment with ibrutinib reduces cytokine secretion and limits the risk of obinutuzumab-induced infusion-related reactions in patients with CLL: analysis from the iLLUMINATE study

Greil, Richard
Autor Greil, Richard IIIrd Medical Department Paracelsus Medical University, Salzburg Cancer Research Institute-CCCIT, Cancer Cluster Salzburg, Salzburg, Austria. r.greil@salk.at
Tedeschi, Alessandra
Autor Tedeschi, Alessandra Department of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
Moreno, Carol
Autor Moreno, Carol Department of Hematology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain
Anz, Bertrand
Autor Anz, Bertrand Department of Medical Oncology, Tennessee Oncology, Chattanooga, TN, USA
Larratt, Loree
Autor Larratt, Loree Department of Clinical Hematology, University of Alberta Hospital, Edmonton, Alberta, Canada
Simkovic, Martin
Autor Simkovic, Martin Department of Internal Medicine - Hematology, University Hospital and Medical School Hradec Králové, Hradec Králové, Czech Republic
Gill, Devinder
Autor Gill, Devinder Department of Clinical Hematology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
Gribben, John G
Autor Gribben, John G Centre for Haemato-Oncology, Queen Mary University of London, Barts Cancer Institute, London, UK
Flinn, Ian W
Autor Flinn, Ian W Center for Blood Cancers, Medical Oncology, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN, USA
Wang, Zhengyuan
Autor Wang, Zhengyuan Translational Medicine, Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA, USA

Annals of hematology. 2021 ; 100 (7) : 1733-1742. [pub] 20210520

Ann Hematol
ISSN 1432-0584
Medvik
Zdroj

Anti-CD20 antibody treatments, such as obinutuzumab, have been associated with infusion-related reactions (IRRs). In the phase 3 iLLUMINATE study of ibrutinib-obinutuzumab versus chlorambucil-obinutuzumab in first-line chronic lymphocytic leukemia/small lymphocytic lymphoma, IRRs were substantially reduced with ibrutinib-obinutuzumab versus chlorambucil-obinutuzumab. We prospectively analyzed inflammatory cytokines to evaluate the impact of ibrutinib on circulating cytokine levels following obinutuzumab infusion. In iLLUMINATE, ibrutinib or chlorambucil was given approximately 30-120 min before the first obinutuzumab infusion. Cytokines evaluated were IFNγ, IL-6, IL-8, IL-10, IL-18, MCP-1, MIP-1α, MIP-1β, and TNFα. Changes in peak cytokine levels from baseline (immediately before obinutuzumab) to post-obinutuzumab infusion were compared between arms and between patients with versus without IRRs using Wilcoxon rank sum test. Of 228 treated patients, 95 on ibrutinib-obinutuzumab (15 with IRRs, 80 without) and 88 on chlorambucil-obinutuzumab (45 with IRRs, 43 without) with cytokine data were included. Irrespective of IRR occurrence, median increase in cytokines was lower with ibrutinib-obinutuzumab versus chlorambucil-obinutuzumab for all cytokines (P < 0.01) except MIP-1β. Across treatment arms, post-obinutuzumab median increase in all cytokines except MIP-1β was greater in patients with versus without IRRs (P < 0.001). IL-6 and IL-8 elevations were associated with IRRs in both treatment arms. Among patients with IRRs, those receiving ibrutinib-obinutuzumab had lower post-obinutuzumab increases in IL-6, IL-8, IL-10, and MCP-1 (P < 0.04) than patients receiving chlorambucil-obinutuzumab. For patients in the ibrutinib-treatment arm, we observed a reduction in both the rate of clinically apparent IRRs and the levels of IRR-related cytokines and chemokines. This observation supports an immunomodulatory mechanism of action for ibrutinib. Clinical Trial Registration: NCT02264574.

Článek

Strategie "watch and wait" u pacientů s chronickou lymfocytární leukemií

Acta medicinae. 2020 ; 9 (11-13) : 102-104.

ISSN 1805-398X
Medvik
Zdroj

Klíčová slova
fludarabin, ibrutinib,
MeSH
antitumorózní látky aplikace a dávkování MeSH
chlorambucil aplikace a dávkování MeSH
chronická lymfatická leukemie * farmakoterapie terapie MeSH
klinická studie jako téma MeSH
klinické rozhodování MeSH
lidé MeSH
pozorné vyčkávání * MeSH
progrese nemoci MeSH
randomizované kontrolované studie jako téma MeSH
výsledek terapie MeSH
Check Tag
lidé MeSH
Publikační typ
práce podpořená grantem MeSH

Článek

Real-world data on efficacy and safety of obinutuzumab plus chlorambucil, rituximab plus chlorambucil, and rituximab plus bendamustine in the frontline treatment of chronic lymphocytic leukemia: The GO-CLLEAR Study by the Czech CLL Study Group

Hematological oncology. 2020 ; 38 (4) : 509-516. [pub] 20200601

Hematol Oncol
ISSN 1099-1069
Medvik
Zdroj

Until recently, a combination of anti-CD20 antibody plus less intensive chemotherapy was a standard of care in elderly population with previously untreated chronic lymphocytic leukemia (CLL). The aim of this observational study was to retrospectively assess efficacy and safety of obinutuzumab + chlorambucil (G-Clb), rituximab + chlorambucil (R-Clb), and bendamustine + rituximab (BR) given as the frontline therapy within routine practice. The final analyzed dataset included 398 consecutive CLL patients from 10 hematology centers cooperating within the Czech CLL Study Group: 63 treated with G-Clb, 78 with R-Clb, and 257 with BR. There were no significant differences in prognostic and predictive markers among the groups. On the contrary, median age at the start of therapy and cumulative illness rating scale (CIRS) score was significantly higher in R-Clb group. Obinutuzumab plus chlorambucil regimen was preferably offered to elderly patients (compared to BR) with less severe comorbidities and lower CIRS score (compared to R-Clb). A time period when a treatment was indicated had also a strong impact on the choice of the regimen. The overall response rate reached 76% (30% complete remissions, CRs) in G-Clb, 75% (22% CRs) in R-Clb, and 85% (47% CRs) in BR group. Median event-free survival was 49.0 months for G-Clb, 20.3 months for R-Clb, and 37.0 months for BR group. Neutropenia grade ≥ 3 developed in 43% of G-Clb, 31% of R-Clb and in 49% of BR patients, grade ≥ 3 infections were recorded in 17% of G-Clb, 6.4% of R-Clb, and 17% of BR patients. In conclusion, real-world therapeutic activity of G-Clb appears to be at least comparable to prospective clinical trial data. R-Clb yields relatively good results in very old and severely comorbid patients.

Článek

A five-year follow-up of untreated patients with chronic lymphocytic leukaemia treated with ofatumumab and chlorambucil: final analysis of the Complement 1 phase 3 trial

British journal of haematology. 2020 ; 190 (5) : 736-740. [pub] 20200331

Br J Haematol
ISSN 1365-2141
Medvik
Zdroj

The Complement 1 trial investigated the efficacy and safety of ofatumumab + chlorambucil with chlorambucil monotherapy in patients with previously untreated chronic lymphocytic leukaemia (CLL). On long-term follow-up in the chemoimmunotherapy arm vs. the chemotherapy arm there was an estimated 12% (not significant) and 39% risk reduction in overall survival and progression-free survival, respectively. A high rate (61%) of treatment with next-line therapies in both the treatment arms may dilute any potential OS difference and confound the interpretation of the OS results. Addition of ofatumumab to chlorambucil demonstrated clinical benefit and tolerability as a frontline treatment option in patients unfit for fludarabine-containing therapy, with no new safety concerns.

Článek

Frontline treatment with the combination obinutuzumab ± chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group

American journal of hematology. 2020 ; 95 (6) : 604-611. [pub] 20200314

Am J Hematol
ISSN 1096-8652
Medvik
Zdroj

In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O ± Clb in unfit patients with CLL, in a "real-world" setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a "real-world" setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease.

Článek

Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial

Lancet oncology. 2019 ; 20 (1) : 43-56. [pub] 20181203

Lancet Oncol.
ISSN 1474-5488
Medvik
Zdroj

BACKGROUND: Both single-agent ibrutinib and chlorambucil plus obinutuzumab have shown superior efficacy to chlorambucil monotherapy and are standard first-line treatments in chronic lymphocytic leukaemia. We compared the efficacy of the combination of ibrutinib plus obinutuzumab with chlorambucil plus obinutuzumab in first-line chronic lymphocytic leukaemia or small lymphocytic lymphoma. METHODS: iLLUMINATE is a multicentre, randomised, open-label, phase 3 trial done at 74 academic and community hospitals in Australia, Canada, Israel, New Zealand, Russia, Turkey, the EU, and the USA in patients with previously untreated chronic lymphocytic leukaemia or small lymphocytic lymphoma, either aged 65 years or older or younger than 65 years with coexisting conditions. Patients were randomly assigned (1:1) using a blocked randomisation schedule, stratified by Eastern Cooperative Oncology Group performance status and cytogenetics, to receive ibrutinib plus obinutuzumab (oral ibrutinib [420 mg once daily continuously] combined with intravenous obinutuzumab [100 mg on day 1, 900 mg on day 2, 1000 mg on day 8, and 1000 mg on day 15 of cycle 1 and on day 1 of subsequent 28-day cycles, for a total of six cycles]) or chlorambucil plus obinutuzumab (oral chlorambucil [0·5 mg/kg bodyweight on days 1 and 15 of each 28-day cycle for six cycles] combined with the same obinutuzumab regimen). Allocation concealment was achieved using an interactive web response system. Patients and investigators were not masked to treatment assignment. The primary endpoint was progression-free survival assessed by a masked independent review committee in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov (NCT02264574), and patient enrolment is complete. FINDINGS: Between Oct 6, 2014, and Oct 12, 2015, 229 patients were enrolled and randomly assigned to receive ibrutinib plus obinutuzumab (n=113) or chlorambucil plus obinutuzumab (n=116). After a median follow-up of 31·3 months (IQR 29·4-33·2), median progression-free survival was significantly longer in the ibrutinib plus obinutuzumab group (median not reached [95% CI 33·6-non-estimable]) than in the chlorambucil plus obinutuzumab group (19·0 months [15·1-22·1]; hazard ratio 0·23; 95% CI 0·15-0·37; p<0·0001). Estimated 30-month progression-free survival was 79% (95% CI 70-85) in the ibrutinib plus obinutuzumab group and 31% (23-40) in the chlorambucil plus obinutuzumab group. The most common grade 3 or 4 adverse events in both groups were neutropenia and thrombocytopenia. Serious adverse events occurred in 65 (58%) of 113 patients treated with ibrutinib plus obinutuzumab and 40 (35%) of 115 patients treated with chlorambucil plus obinutuzumab. Ibrutinib or chlorambucil treatment-related deaths were reported in one (1%) of 113 patients in the ibrutinib plus obinutuzumab group (sudden death) and one (1%) of 115 patients in the chlorambucil plus obinutuzumab group (neuroendocrine carcinoma of the skin). INTERPRETATION: Ibrutinib plus obinutuzumab is an efficacious and safe chemotherapy-free combination treatment in previously untreated patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma independent of high-risk features and provides an alternative first-line treatment option for these patients. FUNDING: Pharmacyclics LLC, an AbbVie Company, and Janssen Research and Development.

Článek

Composite lymphoma of concurrent T zone lymphoma and large cell B cell lymphoma in a dog

BMC veterinary research. 2019 ; 15 (1) : 413. [pub] 20191116

BMC vet. res.
ISSN 1746-6148
Medvik
Zdroj

BACKGROUND: Evolution of indolent to aggressive lymphoma has been described in dogs but is difficult to distinguish from the de novo development of a second, clonally distinct lymphoma. Differentiation of these scenarios can be aided by next generation sequencing (NGS)-based assessment of clonality of lymphocyte antigen receptor genes. CASE PRESENTATION: An 8-year-old male intact Mastiff presented with generalized lymphadenomegaly was diagnosed with nodal T zone lymphoma (TZL) based on cytology, histopathology, immunohistochemistry and flow cytometry. Thirteen months later, the dog re-presented with progressive lymphadenomegaly, and based on cytology and flow cytometry, a large B cell lymphoma (LBCL) was diagnosed. Sequencing-based clonality testing confirmed the de novo development of a LBCL and the persistence of a TZL. CONCLUSIONS: The occurrence of two distinct lymphoid neoplasms should be considered if patient features and tumor cytomorphology or immunophenotype differ among sequential samples. Sequencing-based clonality testing may provide conclusive evidence of two concurrent and distinct clonal lymphocyte populations, termed most appropriately "composite lymphoma".