Tadeusz Robak

Medical University of Łódź, Łódź, Łódź Voivodeship, Poland

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Publications (611)1757.83 Total impact

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    Full-text · Dataset · Feb 2016
  • Tadeusz Robak · Jerzy Z. Blonski · Pawel Robak

    No preview · Article · Feb 2016
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    Full-text · Article · Jan 2016
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    ABSTRACT: Background: Chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. Methods: We randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee. Results: The median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P<0.001). Ibrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P=0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, P<0.001). The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib. Conclusions: Ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall survival, response rate, and improvement in hematologic variables. (Funded by Pharmacyclics and others; RESONATE-2 ClinicalTrials.gov number, NCT01722487.).
    Full-text · Article · Dec 2015 · New England Journal of Medicine
  • Tadeusz Robak

    No preview · Article · Dec 2015 · The Lancet Oncology
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    ABSTRACT: Introduction: Ofatumumab, the first fully human IgG1κ, belongs to the second generation of the first class of anti-CD20 monoclonal antibodies. The drug used alone and in combination with drugs having different mechanisms of action has shown a favorable toxicity profile and significant benefit especially in relapsed/refractory chronic lymphocytic leukemia (CLL) patients in doses up to 2000 mg. Areas covered: This article reviews pharmacokinetic, clinical application for CLL treatment, and safety profile of ofatumumab as well as differences and similarity between ofatumumab and rituximab. Publications in English from 2010 through October 2015 were surveyed on the MEDLINE database for articles. Proceedings of the American Society of Hematology held during the last 5 years were also included. Expert opinion: Ofatumumab more effectively than rituximab enhanced complement-dependent cytotoxicity playing the crucial role for its therapeutic activity. The drug is highly effective in the first-line and salvage treatment of CLL, essentially as a part of immunochemotherapy, and probably also as maintenance therapy. Its safety profile is very advantageous, since adverse events are usually limited to grade 1 and 2 infusion-related reactions, which tend to decrease throughout the treatment. Its advantage over the other anti-CD20 monoclonal antibodies in the treatment of CLL remains to be determined in the direct head-to-head trials.
    No preview · Article · Nov 2015 · Expert Opinion on Drug Safety
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    ABSTRACT: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease. Various disease-related and patient-related factors have been shown to influence the course of the disease. The aim of this study was to identify novel biomarkers of significant clinical relevance. Pretreatment CD19-separated lymphocytes (n=237; discovery set) and peripheral blood mononuclear cells (n=92; validation set) from the REACH trial, a randomized phase III trial in relapsed CLL comparing rituximab plus fludarabine plus cyclophosphamide with fludarabine plus cyclophosphamide alone, underwent gene expression profiling. By using Cox regression survival analysis on the discovery set, we identified inositol polyphosphate-5-phosphatase F (INPP5F) as a prognostic factor for progression-free survival (P<0.001; hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.35–1.98) and overall survival (P<0.001; HR, 1.47; 95% CI, 1.18–1.84), regardless of adjusting for known prognostic factors. These findings were confirmed on the validation set, suggesting that INPP5F may serve as a novel, easy-to-assess future prognostic biomarker for fludarabine-based therapy in CLL.
    Preview · Article · Oct 2015 · Blood Cancer Journal
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    ABSTRACT: Badania in vitro nad wpływem bendamustyny zastosowanej pojedynczo lub w skojarzeniu z rytuksymabem na komórki przewlekłej białaczki limfocytowej z uwzględnieniem stanu mutacyjnego IGVH. Warunki hodowli komórkowych Komórki PBL inkubowano z badanymi lekami przez 48 godzin w medium hodowlanym RPMI 1640, zawierającym 10% (v/v) inaktywowanej FCS + 10% (v/v) surowicy autologicznej, w temperaturze 37 °C, w atmosferze 5% CO 2 i pełnej wilgotności. Hodowlę kontrolną wykonywano bez dodatku badanych leków. Ocena wpływu leków na apoptozę Odsetek komórek apoptotycznych oceniono cytometrycznie testem z aneksyną-V (ANN) i jodkiem propidyny (JP) po 48-godzinnej inkubacji. Apoptoza indukowana lekiem (AIL) = (% komórek apoptotycznych po inkubacji z badanymi lekami) – (% komórek apoptotycznych w hodowli kontrolnej). Nekroza indukowana lekiem (NIL) = (% komórek nekrotycznych po inkubacji z lekami) – (% komórek nekrotycznych w hodowli kontrolnej). Ocena zmian potencjału mitochondrialnego(∆Ψm) ∆Ψm oceniono przy użyciu zestawu MitoTracker Red CMX Ros (inkubacja 30 min., 37°C) i analizowano w cytometrze przepływowym (FACSCalibour, Becton Dickinson, USA). ∆Ψm indukowane lekiem (∆ΨmIL) = (% komórek wykazujących ∆Ψm po inkubacji z lekami) – (% komórek wykazujących ∆Ψm w hodowli kontrolnej).
    Full-text · Conference Paper · Sep 2015
  • Piotr Smolewski · Magdalena Witkowska · Tadeusz Robak
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    ABSTRACT: Introduction: In this article, we provide an accurate overview of both standard treatment option and novel promising therapeutics. Major impact is on novel agents now being tested in randomized clinical trials. While the initial data are promising, they may rapidly expand treatment options, change existing paradigms and further improve outcomes for mantle cell lymphoma (MCL) patients. Areas covered: MCL is a disease with indolent histology, but aggressive clinical course. However, for now, MCL remains incurable and the search for the most effective and tumor-specific treatment still represents a great challenge for oncohematologists. However, the implementation of chemotherapy together with the anti-CD20 antibody rituximab, as well as the growing use of autologous stem cell transplantation in first remission, have improved effects of treatment in MCL, including even some improvement in overall survival. Recently, treatment modalities for MCL have been expanded by strategies based on several biologically targeted agents, including m-TOR kinase or proteasome inhibitors and immunomodulatory agents, such as lenalidomide. B-cell receptor pathway inhibitors, such as ibrutinib and idelalisib, and histone deacetylase or cyclin-dependent kinase inhibitors have also shown promising activity in resistant or relapsed disease. Expert opinion: Although enormous progress was made in the treatment of MCL over the last year, the disease remains incurable. One chance for the significant life prolongation is intensive treatment with consolidative auto SCT. However, real progress may be afforded by developing the novel agents described in this article. In this way, MCL may soon become another potentially curable oncological malignancy.
    No preview · Article · Sep 2015 · Expert Opinion on Pharmacotherapy
  • Tadeusz Robak
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    ABSTRACT: Mantle cell lymphoma (MCL) is a hematological malignancy with unfavorable prognosis. Bortezomib, a potent, selective and reversible inhibitor of the 26S proteasome, was shown to be active in MCL and is currently implemented in therapeutic combinations. Single-agent bortezomib has demonstrated clinical efficacy in relapsed and refractory MCL with objective response in up to 47% of the patients. However, complete remission rates are low and duration of response is relatively short. In previously untreated patients, the addition of bortezomib to induction chemotherapy is also promising. Further evaluation of bortezomib alone or in combination with other drugs for the treatment of MCL is warranted to improve the quality of life and survival of patients. This review explores bortezomib as therapy in patients with MCL.
    No preview · Article · Sep 2015 · Future Oncology

  • No preview · Article · Sep 2015 · Acta haematologica Polonica

  • No preview · Article · Sep 2015
  • T. Robak

    No preview · Article · Sep 2015 · Acta haematologica Polonica
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    ABSTRACT: European Scientific Journal Background Many prognostic factors have been identified in chronic lymphocytic leukemia (CLL) but new ones are still desired. The biological characterization of CLL is now being translated into novel treatment strategies. One new prognostic factor, and therapeutic target, may be BFL1. It is both a serum and a molecular marker that contributes to the progression of CLL and its resistance to chemotherapy. The aim of this study was to evaluate the prognostic value of BFL1 and to assess its correlation with other known prognostic markers in CLL for the cladribine and cyclophosphamide regimen (CC). Methods qPCR TaqMan® Low Density Array was used for gene expression measurements. Assessment of CD38, ZAP70 and BFL-1 proteins expression was done by means of flow cytometry. Serum TK activity was measured by immunoassay. Results Protein BFL1 expression was found to be significantly higher in CLL patients than healthy volunteers (p=0.001). Moreover its level was significantly higher in patients with no response (NR) to CC therapy (p=0.009). The expression of BFL1 was considerably down regulated during CC treatment and BFL1 mRNA levels were inversely correlated with apoptotic response. In addition, protein BFL1 expression was found to be similar to thymidine kinase (TK) concentration regarding treatment response. As far as other markers are concerned, a positive correlation was identified between BFL1 and TK (r=0.52, p=0.01). Conclusions Our findings suggest that BFL1 contributes to chemoresistance and may be a co-existing prognostic factor in CLL in the future.
    Full-text · Article · Sep 2015
  • Tadeusz Robak · Anna Wolska · Pawel Robak
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    ABSTRACT: Introduction: Hairy cell leukemia (HCL) is a rare subtype of B-cell chronic lymphoid leukemia. It is characterized by progressive pancytopenia, splenomegaly and infiltrations of the bone marrow, liver and spleen. Over the last few years, several new immunological drugs, particularly immunotoxins, BRAF inhibitors and B-cell receptor (BCR) pathway inhibitors have been developed and investigated as potential treatment options. Areas covered: This article summarizes recent investigational therapies of HCL, looking at their: mechanism of action, pharmacological properties, clinical activity and toxicity, as well as their emerging role in its treatment. The authors conducted a literature review of the MEDLINE database for articles in English concerning immunotoxins, BRAF inhibitors and BCR pathway inhibitors via PubMed. Publications from 2000 through to June 2015 were scrutinized. The search terms used were: BRAF, vemurafenib, dabrafenib, ibrutinib, monoclonal antibodies, immunotoxins, moxetumomab pasudotox, and rituximab in conjunction with HCL. The authors also searched manually the conference proceedings from the previous 5 years of the American Society of Hematology, European Hematology Association, American Society of Clinical Oncology, and ACR/ARHP Annual Scientific Meetings were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles. Expert opinion: The use of vemurafenib and moxetumomab pasudotox is a promising new strategy for the treatment of HCL. Data from ongoing and future clinical trials will aid in better defining the status of new drugs in the treatment of HCL.
    No preview · Article · Aug 2015 · Expert Opinion on Investigational Drugs
  • Tadeusz Robak · Piotr Smolewski
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    ABSTRACT: In this issue of Blood, Dietrich et al make the first observation of the presence of deleterious CDKN1B mutation in 16% of patients with hairy cell leukemia (HCL).1 Furthermore, in the majority of patients, the CDKN1B mutation was clonal, suggesting that this mutation plays a role in the pathogenesis of HCL.
    No preview · Article · Aug 2015 · Blood
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    Preview · Article · Aug 2015 · Annals of Oncology
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    ABSTRACT: Introduction: Small molecule inhibitors are currently in various stages of preclinical and clinical trials and are expected to revolutionize the treatment of many neoplastic diseases, including B-cell lymphoid malignancies. Areas covered: This article reviews the chemical structure, mechanisms of action, pharmacodynamic and pharmacokinetic properties, as well as clinical applications of small molecules in the treatment of elderly patients with B-cell hematological malignancies. Bibliographic research covering mainly the period from 2010 until February 2015 was conducted on the MEDLINE database for articles in English. Proceedings of the American Society of Hematology, European Hematology Association and American Society of Clinical Oncology conferences held during the last 5 years were also included. Expert opinion: In the last few years, several preclinical and clinical trials have evaluated many small weight organic molecules which downregulate B-cell receptor (BCR) signaling and act via inhibition of either BCR-associated kinases or cyclin-dependent kinases, or which are antagonists of members of the B-cell lymphoma 2 protein family. Pharmacokinetic profiles of these agents as well as dosage used and adverse events in patients with lymphoid malignancies have been established. Some of these inhibitors satisfy therapeutic modalities as suitable for the elderly patients, including those with chronic lymphocytic leukemia and non-Hodgkin's lymphoma.
    No preview · Article · Jul 2015 · Expert Opinion on Drug Metabolism & Toxicology
  • Pawel Robak · Piotr Smolewski · Tadeusz Robak
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    ABSTRACT: Introduction: Over the last few years, several new immunological drugs, particularly monoclonal antibodies (mAbs), immunomodulatory drugs and B-cell receptor (BCR) pathway inhibitors have been developed and investigated in chronic lymphocytic leukemia (CLL). This article summarizes recent discoveries regarding their mechanism of action, pharmacological properties, clinical activity and toxicity, as well as the emerging role of these agents in CLL. Areas covered: A literature review of mAbs, BCR pathway inhibitors and immunomodulating drugs was conducted of the MEDLINE database via PubMed for articles in English. Publications from 2000 through February 2015 were scrutinized. The search terms used were alemtuzumab, BI 836826, duvelisib ibrutinib, idelalisib, lenalidomide, monoclonal antibodies, MEDI-551, MOR208, obinutuzumab, ocaratuzumab, ofatumumab, ONO-4059, otlertuzumab, spebrutinib, veltuzumab and XmAb5574 in conjunction with CLL. Conference proceedings from the previous 5 years of the American Society of Hematology, European Hematology Association, American Society of Clinical Oncology, and ACR/ARHP Annual Scientific Meetings were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles. Expert opinion: The use of mAbs, BCR inhibitors and immunomodulating drugs is a promising new strategy for chemotherapy-free treatment of CLL. However, definitive data from ongoing and future clinical trials will aid in better defining the status of immunological drugs in the treatment of this disease.
    No preview · Article · Jul 2015 · Expert Opinion on Emerging Drugs
  • Piotr Smolewski · Tadeusz Robak
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    ABSTRACT: Introduction: Monoclonal antibodies (MoAbs) were developed in the 1980s in order to treat malignancies. An important target for MoAbs was the CD20 B-cell lineage antigen. Rituximab (RTX) is a chimeric mouse anti-human MoAb that targets the CD20 antigen on the surface of malignant and normal B lymphocytes, and has rapidly become the widest used immunotherapeutic drug. RTX has had a significant impact on how B-cell non-Hodgkin's lymphomas (NHLs) and chronic lymphocytic leukemia is now treated. Areas covered: In this review, the authors demonstrate the mechanisms of action of RTX, and the preclinical data that have led to clinical trials and its final approval for the treatment of B-cell NHLs. Expert opinion: The discovery of RTX opened a new era for treatment of B-cell malignancies and became the starting point for the development of new, more active classes of anti-CD20 agents. Furthermore, it has contributed to the construction of a number of MoAbs specific for other antigens that target different types of neoplastic cells.
    No preview · Article · Jun 2015 · Expert Opinion on Drug Discovery

Publication Stats

10k Citations
1,757.83 Total Impact Points

Institutions

  • 1994-2015
    • Medical University of Łódź
      Łódź, Łódź Voivodeship, Poland
  • 1992-2015
    • University of Lodz
      • Department of Cytobiochemistry
      Łódź, Łódź Voivodeship, Poland
  • 2005-2013
    • Wojewódzki Szpital Specjalistyczny im. M. Kopernika w Łodzi
      Łódź, Łódź Voivodeship, Poland
  • 2007
    • Clinical Hospital Merkur
      Zagrabia, Grad Zagreb, Croatia
  • 2004
    • Medical University of Gdansk
      Danzig, Pomeranian Voivodeship, Poland
  • 2002
    • Centre Hospitalier Lyon Sud
      Lyons, Rhône-Alpes, France
  • 2001
    • Medical University of Warsaw
      • Katedra i Klinika Pediatrii, Hematologii i Onkologii
      Warsaw, Masovian Voivodeship, Poland
  • 1997
    • Medical University of Lublin
      Lyublin, Lublin Voivodeship, Poland