Preliminary safety and efficacy of the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib (IBR) in patients (pts) with hairy cell leukemia (HCL).

Wolska

Expert Opinion on Investigational Drugs

2015

Section: Bcr Signaling Inhibitorsmentioning

confidence: 96%

“…The patient remained in CR for 6 months after completion of the treatment with a very good quality of life [79]. [99] Ibrutinib 420 --840 mg daily in 28-day cycles for a median of 16 weeks Previously treated (11 relapsed, 1 untreated, 1 with HCL-v), median prior therapies -4 (range: 1 --11)…”

Section: Braf Inhibitorsmentioning

confidence: 99%

Potential breakthroughs with investigational drugs for hairy cell leukemia

Wolska

Expert Opinion on Investigational Drugs

2015

“…This phenomenon is due to rapid ( 24 h after drug intake) egress and mobilization of lymphoid cells residing in the protective tissue niches. Only preliminary clinical data with ibrutinib in HCL are available [74].…”

Section: Bcr Signaling Kinase Inhibitorsmentioning

confidence: 99%

“…A clinical trial of ibrutinib in patients with relapsed HCL has recently been initiated. Preliminary safety and efficacy data were presented at the annual American Society of Clinical Oncology (ASCO) meeting in 2014 [74]. Eight patients (one untreated, one relapsed HCLv and six with relapsed classical HCL) were treated with ibrutinib at 420 mg daily in 28-day cycles.…”

Section: Ibrutinib: Btk Inhibitormentioning

confidence: 99%

Novel therapeutic options for relapsed hairy cell leukemia

Jain

Polliack²,

Ravandi

2015

Leukemia & Lymphoma

The majority of patients with hairy cell leukemia (HCL) achieve a response to therapy with cladribine or pentostatin with or without rituximab. However, late relapses can occur. Treatment of relapsed HCL can be difficult due to a poor tolerance to chemotherapy, increased risk of infections and decreased responsiveness to chemotherapy. The identification of BRAFV600E mutations and the role of aberrant MEK kinase and Bruton's tyrosine kinase (BTK) pathways in the pathogenesis of HCL have helped to develop novel targeted therapies for these patients. Currently, the most promising therapeutic strategies for relapsed or refractory HCL include recombinant immunoconjugates targeting CD22 (e.g. moxetumomab pasudotox), BRAF inhibitors such as vemurafenib and B cell receptor signaling kinase inhibitors such as ibrutinib. Furthermore, the VH4-34 molecular variant of classic HCL has been identified to be less responsive to chemotherapy. Herein, we review the results of the ongoing clinical trials and potential future therapies for relapsed/refractory HCL.

“… 59 In addition, Btk has recently been identified as a promising target in patients with HCL and clinical trials investigating the Btk inhibitor ibrutinib in these patients are ongoing. 60 , 61 …”

Section: Hairy Cell Leukemiamentioning

confidence: 99%

Role of Tyrosine Kinase Inhibitors in Indolent and Other Mature B-Cell Neoplasms

et al. 2015

Targeting tyrosine kinases represents a highly specific treatment approach for different malignancies. This also includes non-Hodgkin lymphoma since it is well known that these enzymes are frequently involved in the lymphomagenesis. Hereby, tyrosine kinases might either be dysregulated intrinsically or be activated within signal transduction pathways leading to tumor survival and growth. Among others, Bruton’s tyrosine kinase (Btk) is of particular interest as a potential therapeutic target. Btk is stimulated by B-cell receptor signaling and activates different transcription factors such as nuclear factor κB. The Btk inhibitor ibrutinib has been approved for the treatment of chronic lymphocytic leukemia and mantle-cell lymphoma recently. Numerous clinical trials evaluating this agent in different combinations (eg, with rituximab or classical chemotherapeutic agents) as a treatment option for aggressive and indolent lymphoma are under way. Here, we summarize the role of tyrosine kinase inhibitors in the treatment of indolent and other non-Hodgkin lymphomas (eg, mantle-cell lymphoma).