94 results match your criteria ibrutinib salvage

Ibrutinib monotherapy for relapse or refractory primary CNS lymphoma and primary vitreoretinal lymphoma: Final analysis of the phase II 'proof-of-concept' iLOC study by the Lymphoma study association (LYSA) and the French oculo-cerebral lymphoma (LOC) network.

Eur J Cancer 2019 08 3;117:121-130. Epub 2019 Jul 3.

APHP, Sorbonne Université, IHU, ICM, Neurology,Groupe Hospitalier Pitié-Salpêtrière, Paris, France.

Background: Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal centre B-cell subtype, with unmet medical needs. This study aimed to evaluate the efficacy and toxicity of ibrutinib in DLBCL-PCNSL PATIENTS AND METHODS: This prospective, multicentre, phase II study involved patients with relapse or refractory(R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma. The treatment consisted of ibrutinib (560 mg/day) until disease progression or unacceptable toxicity occurred. Read More

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Bruton tyrosine kinase inhibitors for the treatment of mantle cell lymphoma: review of current evidence and future directions.

Clin Adv Hematol Oncol 2019 Apr;17(4):223-233

Arthur G. James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, Ohio.

Mantle cell lymphoma (MCL) is a heterogeneous and uncommon non-Hodgkin lymphoma that affects predominantly older patients and often is associated with an aggressive clinical course. MCL relies upon B-cell receptor signaling through Bruton tyrosine kinase (BTK); therefore, the development of the BTK inhibitors ibrutinib and acalabrutinib represents a therapeutic breakthrough. In this review, we provide a summary of the efficacy and safety data from the landmark trials of single-agent ibrutinib and acalabrutinib that led to US Food and Drug Administration approval of these agents for patients with relapsed or refractory MCL. Read More

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Duvelisib: a new phosphoinositide-3-kinase inhibitor in chronic lymphocytic leukemia.

Future Oncol 2019 Jul 29;15(19):2227-2239. Epub 2019 May 29.

Department of Hematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, Milano, Italy.

P110-γ and -δ act in lymphocytes chemotaxis, presenting distinct, nonredundant roles in B- and T-cell migration and adhesion to stromal cells. Moreover, phosphoinositide-3-kinase-γ inhibition contributes to regulate macrophage polarization inhibiting cancer growth. Duvelisib (IPI-145) is an oral first-in-class, dual phosphoinositide-3-kinase inhibitor targeting p110-δ/γ exerting its activity in preclinical studies across different prognostic groups. Read More

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Relapsed/Refractory Chronic Lymphocytic Leukemia: Chemoimmunotherapy, Treatment until Progression with Mechanism-Driven Agents or Finite-Duration Therapy?

Mediterr J Hematol Infect Dis 2019 1;11(1):e2019024. Epub 2019 Mar 1.

Hematology, Department of Cellular Biotechnologies and Hematology, Policlinico Umberto 1, 'Sapienza' University, Rome, Italy.

Treatment of relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) has dramatically improved thanks to the development of mechanism-driven agents including drugs that inhibit kinases in the BCR pathway or BCL2. The treating physician has now the opportunity to decide i) which patient can be still offered chemoimmunotherapy as salvage treatment, ii) which patient at relapse is a candidate to receiving, continuous treatment with ibrutinib, idelalisib and rituximab or venetoclax and iii) which patient may benefit from a fixed-duration treatment using the BCL2 antagonist venetoclax in association with rituximab. Ibrutinib is the most actively investigated drug in R/R CLL and data at a 7-year follow-up were reported, showing durable efficacy and favorable efficacy profile. Read More

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How I manage ibrutinib intolerance and complications in patients with chronic lymphocytic leukemia.

Blood 2019 03 14;133(12):1298-1307. Epub 2019 Jan 14.

Division of Hematology, Department of Internal Medicine.

Chronic lymphocytic leukemia (CLL) therapy has changed dramatically with the introduction of several targeted therapeutics. Ibrutinib was the first approved for use in 2014 and now is used for initial and salvage therapy of CLL patients. With its widespread use in clinical practice, ibrutinib's common and uncommon adverse events reported less frequently in earlier clinical trials have been experienced more frequently in real-world practice. Read More

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The magnitude of improvement in progression-free survival with targeted therapy in relapsed/refractory chronic lymphocytic leukemia based on prognostic risk category: a systematic review and meta-analysis.

Leuk Lymphoma 2019 07 5;60(7):1644-1649. Epub 2018 Dec 5.

c Department of Medicine, Division of Hematology , Stanford University , Stanford , CA , USA.

Chronic lymphocytic leukemia (CLL) guidelines highlight the relevance of cytogenetic and molecular testing to identify patients with high-risk genetic features. However, at the moment, only 17p del/ mutation are universally recognized parameters influencing choice of therapy. We conducted a systematic review and meta-analysis assessing the magnitude of improvement in progression-free survival (PFS) with B-cell receptor (BCR) (i. Read More

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Introduction of novel agents in the treatment of primary CNS lymphoma.

Neuro Oncol 2019 02;21(3):306-313

Departments of Neurology and Radiation Oncology, Division of Hematology and Oncology, Massachusetts General Hospital, Boston, Massachusetts.

Novel insights into the pathophysiology of primary central nervous system lymphoma (PCNSL) have identified the B-cell receptor and Toll-like receptor pathway as well as immune evasion and suppressed tumor immune microenvironment as a key mechanism in the pathogenesis of PCNSL. Small molecules and novel agents targeting these aberrant pathways have been introduced into clinical trials targeting the recurrent or refractory PCNSL patient population. Agents like the Bruton tyrosine kinase (BTK) inhibitor ibrutinib or immunomodulatory drugs (IMiDs) like pomalidomide and lenalidomide have shown promising high response rates in the salvage setting. Read More

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February 2019

The rationale for combination therapy in patients with aggressive B-cell non-Hodgkin lymphoma: ten questions.

Future Oncol 2019 Jan 3;15(3):305-317. Epub 2018 Oct 3.

Global Medical Affairs Oncology, Servier, 50, rue Carnot, Suresnes, France.

Rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone immunochemotherapy remains standard of care for first-line treatment of diffuse large B-cell lymphoma (DLBCL). High-dose chemotherapy and stem cell transplantation is offered to most relapsing/refractory patients who respond to salvage therapy. This Q&A review evaluates recommended management strategies for second and subsequent lines of therapy in patients with DLBCL, outlining the relative efficacies of currently available options including novel agents such as ibrutinib and CAR-T cells. Read More

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January 2019

Is ibrutinib associated with disseminated cryptococcosis with CNS involvement?

Cancer Biol Ther 2019 27;20(2):138-140. Epub 2018 Aug 27.

a Division of Infectious Diseases , Medical College of Wisconsin , Milwaukee , WI , USA.

Chronic lymphocytic leukemia (CLL) is a disorder of B cells that affects humoral as well as cell-mediated immunity. Protection against cryptococcal infections is mounted by an intricate and synchronized interplay of both integral arms of immunity. Whether CLL or small molecule tyrosine kinase inhibitors are independently predisposing hosts to cryptococcal infections remain to be explored. Read More

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Unusual cause of sinusitis and cough.

BMJ Case Rep 2018 Jul 19;2018. Epub 2018 Jul 19.

Pathology Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

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Still a role for second-line chemoimmunotherapy in chronic lymphocytic leukemia?

Jennifer R Brown

Haematologica 2018 07;103(7):1096-1098

CLL Center, Division of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.

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Four-year follow-up of a single arm, phase II clinical trial of ibrutinib with rituximab (IR) in patients with relapsed/refractory mantle cell lymphoma (MCL).

Br J Haematol 2018 08 22;182(3):404-411. Epub 2018 May 22.

Department of Lymphoma and myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Ibrutinib has shown significant activity in patients with relapsed or refractory mantle cell lymphoma (RR-MCL). We report the long-term outcome and safety profile of a single-centre, single arm, open-label, phase 2 study of RR-MCL treated with IR. Overall, the median follow-up time was 47 months (range 1-52 months), median duration on treatment was 16 months (range 1-53 months) and median number of treatment cycles was 17 (range 1-56). Read More

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A CD19/CD3 bispecific antibody for effective immunotherapy of chronic lymphocytic leukemia in the ibrutinib era.

Blood 2018 08 9;132(5):521-532. Epub 2018 May 9.

Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.

The Bruton tyrosine kinase inhibitor ibrutinib induces high rates of clinical response in chronic lymphocytic leukemia (CLL). However, there remains a need for adjunct treatments to deepen response and to overcome drug resistance. Blinatumomab, a CD19/CD3 bispecific antibody (bsAb) designed in the BiTE (bispecific T-cell engager) format, is approved by the US Food and Drug Administration for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Read More

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Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: a GIMEMA, ERIC and UK CLL FORUM study.

Haematologica 2018 07 19;103(7):1209-1217. Epub 2018 Apr 19.

Hematology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Italy.

We performed an observational study on the efficacy of ben-damustine and rituximab (BR) as first salvage regimen in chronic lymphocytic leukemia (CLL). In an intention-to-treat analysis including 237 patients, the median progression-free survival (PFS) was 25 months. The presence of del(17p), unmutated IGHV and advanced stage were associated with a shorter PFS at multivariate analysis. Read More

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Pilot trial of ibrutinib in patients with relapsed or refractory T-cell lymphoma.

Blood Adv 2018 04;2(8):871-876

Memorial Sloan Kettering Cancer Center, New York, NY.

Ibrutinib has previously been shown to inhibit Bruton's tyrosine kinase (BTK) and interleukin-2-inducible T-cell kinase (ITK), which mediate B-cell and T-cell receptor signaling, respectively. BTK inhibition with ibrutinib has demonstrated impressive clinical responses in a variety of B-cell malignancies. Whether ibrutinib inhibition of ITK can lead to clinical response in T-cell malignancies is unknown. Read More

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A phase 1 study of lenalidomide and ibrutinib in combination with rituximab in relapsed and refractory CLL.

Blood Adv 2018 04;2(7):762-768

Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington, DC.

Attempts to improve upon the activity of ibrutinib in chronic lymphocytic leukemia (CLL) include the addition of targeted therapies. The combination of lenalidomide and rituximab demonstrated an overall response rate (ORR) of 66% with a complete response (CR) of 12% in the relapsed/refractory setting. Based on these data, we conducted a phase 1 study of rituximab (R), lenalidomide (L), and ibrutinib (I) in relapsed/refractory CLL. Read More

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Novel therapies for relapsed/refractory mantle cell lymphoma.

Best Pract Res Clin Haematol 2018 03 20;31(1):105-113. Epub 2017 Nov 20.

Department of Hematology/Oncology, University of Virginia, USA. Electronic address:

Mantle cell lymphoma is an aggressive Non-Hodgkin's lymphoma that is considered incurable with standard therapies. Most patients treated with frontline immunochemotherapy relapse within a few years and do not usually respond to salvage chemotherapy. Persistent activation of the B-cell receptor pathway is critical to the pathogenesis of mantle cell lymphoma. Read More

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A phase 1 study of ibrutinib in combination with R-ICE in patients with relapsed or primary refractory DLBCL.

Blood 2018 04 31;131(16):1805-1808. Epub 2018 Jan 31.

Lymphoma Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY.

In the postrituximab era, approximately half of the patients with relapsed or refractory (rel/ref) diffuse large B-cell lymphoma (DLBCL) fail to achieve a chemosensitive response to standard salvage therapy, and are thus ineligible to proceed to autologous stem cell transplantation with curative intent. The Bruton tyrosine kinase inhibitor ibrutinib demonstrates single-agent activity in rel/ref DLBCL, particularly of non-germinal center (non-GC) cell of origin. We conducted a single-center phase 1 study evaluating dose-escalated ibrutinib, in a 3-by-3 design, in combination with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in physiologically transplant-eligible rel/ref DLBCL patients. Read More

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Ibrutinib discontinuation in Waldenström macroglobulinemia: Etiologies, outcomes, and IgM rebound.

Am J Hematol 2018 08 25;93(4):511-517. Epub 2018 Jan 25.

Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts.

Ibrutinib is the first approved therapy for symptomatic patients with Waldenström macroglobulinemia (WM). The reasons for discontinuing ibrutinib and subsequent outcomes have not been previously evaluated in WM patients. We therefore conducted a retrospective review of 189 WM patients seen at our institution who received treatment with ibrutinib, of whom 51 (27%) have discontinued therapy. Read More

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Advances in Diagnosis and Management of Diffuse Large B-cell Lymphoma.

Clin Lymphoma Myeloma Leuk 2017 Dec 7;17(12):783-796. Epub 2017 Nov 7.

Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.

The management of diffuse large B-cell lymphoma (DLBCL) has been gradually evolving since the discovery of its 2 major forms, the germinal center B-like (GCB) and activated B-cell (ABC) types. Although the reference standard for the identification of these cell types is considered gene expression profiling (GEP), currently the only method commercially available is immunohistochemistry (IHC). The application of various IHC-based algorithms and their correlation with GEP and clinical outcome are discussed. Read More

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December 2017

Efficacy and safety of B-cell receptor signaling pathway inhibitors in relapsed/refractory chronic lymphocytic leukemia: a systematic review and meta-analysis of randomized clinical trials.

Leuk Lymphoma 2018 05 11;59(5):1084-1094. Epub 2017 Sep 11.

a Department of Hematology , Medical University of Lodz, Copernicus Memorial Hospital , Lodz , Poland.

Ibrutinib and idelalisib, B-cell receptor (BCR) signaling pathway inhibitors, have been recently approved for use against relapsed/refractory chronic lymphocytic leukemia (CLL). To assess the efficacy and safety of BCR pathway inhibitors in relapsed/refractory CLL, we conducted a systematic review and meta-analysis of five randomized controlled trials (1866 patients). Our study demonstrated that BCR pathway inhibitors significantly prolonged progression-free survival (PFS; pooled HR = 0. Read More

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Dexamethasone, rituximab and cyclophosphamide for relapsed and/or refractory and treatment-naïve patients with Waldenstrom macroglobulinemia.

Br J Haematol 2017 10 8;179(1):98-105. Epub 2017 Aug 8.

Division of Hematology, Mayo Clinic, Rochester, MN, USA.

The management of Waldenström macroglobulinaemia (WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide (DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88 genotype. Read More

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October 2017

Analysis of the risk of infection in patients with chronic lymphocytic leukemia in the era of novel therapies.

Leuk Lymphoma 2018 03 11;59(3):625-632. Epub 2017 Jul 11.

a Wilmot Cancer Institute, University of Rochester , Rochester , NY , USA.

We studied the risk of infections in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Major infections were defined as requiring hospital admission or intravenous antimicrobial treatment. Incidence rate (IR) ratios (IRR) were used to compare infection rates. Read More

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Ibrutinib therapy for lymphoplasmacytic lymphoma.

Am J Hematol 2017 09 9;92(9):E542-E544. Epub 2017 Jun 9.

Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York.

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September 2017