The biology and treatment of chronic lymphocytic leukemia

Palma, Marzia; Kokhaei, Parviz; Lundin, Jeanette; Choudhury, Aniruddha; Mellstedt, Håkan; Österborg, Anders

doi:10.1093/annonc/mdl252

Cited by 24 publications

(23 citation statements)

References 110 publications

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“…Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and is characterized by the accumulation of clonal nonfunctional B lymphocytes in blood, bone marrow, lymph nodes, spleen, and liver (2). The clinical course of disease varies significantly; some patients have indolent disease and survive many years without therapy, whereas others experience rapidly fatal disease (3).…”

Section: Introductionmentioning

confidence: 99%

Phase I Trial of the Pan-PI3K Inhibitor Pilaralisib (SAR245408/XL147) in Patients with Chronic Lymphocytic Leukemia (CLL) or Relapsed/Refractory Lymphoma

Brown

Davids

Rodón

et al. 2015

Clinical Cancer Research

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Purpose: This phase I expansion-cohort study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the pan-PI3K inhibitor pilaralisib (SAR245408/XL147) in patients with chronic lymphocytic leukemia (CLL) or relapsed or refractory lymphoma. Patients and Methods: Patients were treated with the maximum tolerated dose of pilaralisib previously determined in patients with solid tumors (600 mg capsules once daily). Adverse events (AE) and response were evaluated. Plasma pharmacokinetics and pharmacodynamic effects on cytokines and chemokines were also assessed. Results: Twenty-five patients were included in the study: 10 with CLL and 15 with lymphoma. The most frequent AEs of any grade were diarrhea (92.0%), pyrexia (52.0%), and fatigue (44.0%). The most frequent grade ≥3 AEs were neutropenia (32.0%), diarrhea (20.0%), and anemia (16.0%). Pilaralisib exposure on cycle 1 day 28 was similar to exposure in patients with solid tumors. In patients with CLL, pilaralisib significantly reduced plasma levels of several cytokines and chemokines involved in B-cell trafficking. Five patients (50.0%) with CLL and 3 patients (20.0%) with lymphoma had a partial response. Six patients (60.0%) with CLL had nodal shrinkage ≥50%. Overall, 14 patients (56.0%; 7 patients with CLL and 7 patients with lymphoma) had progression-free survival ≥6 months. Conclusions: Pilaralisib demonstrated an acceptable safety profile in patients with CLL and lymphoma, generally consistent with findings in patients with solid tumors. Single-agent pilaralisib showed preliminary clinical activity in patients with CLL and lymphoma, supporting further development. Clin Cancer Res; 21(14); 3160–9. ©2015 AACR.

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Section: Introductionmentioning

confidence: 99%

Phase I Trial of the Pan-PI3K Inhibitor Pilaralisib (SAR245408/XL147) in Patients with Chronic Lymphocytic Leukemia (CLL) or Relapsed/Refractory Lymphoma

Brown

Davids

Rodón

et al. 2015

Clinical Cancer Research

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“…Most cases of CLL are discovered incidentally on blood counts performed for other reasons, showing an elevated white blood count with a preponderance of lymphocytes [10,11]. It is estimated that 5 -10% of patients will present with B symptoms (weight loss of > 10%, fevers, night sweats, fatigue) [10,11].…”

Section: Overview Of Chronic Lymphocytic Leukemiamentioning

confidence: 99%

Bendamustine therapy in chronic lymphocytic leukemia

Masiello

Tulpule

2009

Expert Opinion on Pharmacotherapy

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“…1). It is used for chemotherapy of lymphocytic leukemia, ovarian and breast carcinomas, and Hodgkin's disease [1][2][3]. It is also used as an immunosuppressive drug for the treatment of autoimmune and inflammatory diseases [4].…”

Section: Introductionmentioning

confidence: 99%