Abstract
Chronic lymphocytic leukemia is the most common leukemia in the United States. It is a slowly progressive disease, with an 82% five-year survival rate. The treatment strategies are highly individualized with patients in the early and stable stages typically not requiring treatment. However, those with progressive or clinically advanced disease will require treatment. Cytotoxic drugs, such as the alkylating agents, purine nucleoside antagonists, and immunotherapeutic agents, have been the mainstay of chemotherapeutic treatment in CLL. However, given the lack of therapeutic specificity, these medications (especially older ones) have limited tolerability due to side effects. In this paper, we will discuss the data on the use of phosphatidylinositol 3 kinase inhibitor Idelalisib in the management of patients with chronic lymphocytic leukemia. The preclinical and clinical data thus far demonstrate that Idelalisib produces a dramatic and durable response in patients with chronic lymphocytic leukemia and without causing significant toxicity. Moving forward, the ongoing clinical trials will help address the various questions currently being raised regarding the long-term application and safety of Idelalisib. With greater clinical experience following more widespread use of Idelalisib, we will be able to determine the optimal combination therapies in treatment-naïve and relapsed/refractory patients, resulting in more individualized therapeutic strategies for patients with chronic lymphocytic leukemia.
Highlights
Chronic lymphocytic leukemia (CLL) is a lymphoid malignancy characterized by the accumulation and proliferation of nonfunctional and monoclonal small CD5/CD19/CD20/CD23-positive lymphocytes in the blood, bone marrow, and lymphoid tissues [1, 2]
We focus on the phosphatidylinositol 3 kinase (PI3Kδ) inhibitor Idelalisib (GS-1101, CAL 101), the clinical rationale behind its use in the treatment of CLL, and the outcomes of various preclinical and clinical trials studying the use of Idelalisib alone or in combination with other therapeutic agents for treatment of both initial and relapse/refractory cases of CLL
In the final results reported from a phase I study [33] investigating the clinical activity of Idelalisib in fifty-four patients with relapsed/refractory CLL, being given singleagent oral Idelalisib 50–350 mg/dose, overall response rate (ORR) was 56% including two complete remissions (CR) and twenty-eight partial remissions (PR)
Summary
Chronic lymphocytic leukemia (CLL) is a lymphoid malignancy characterized by the accumulation and proliferation of nonfunctional and monoclonal small CD5/CD19/CD20/CD23-positive lymphocytes in the blood, bone marrow, and lymphoid tissues [1, 2]. Those with progressive or clinically advanced disease will require treatment Cytotoxic drugs, such as the alkylating agents (chlorambucil, cyclophosphamide, and Bendamustine), have been the mainstay of chemotherapeutic treatment in CLL. A treatment regimen combining Fludarabine, cyclophosphamide, and Rituximab (FCR) is currently the gold standard of initial treatment for CLL and has shown response in relapsed/refractory cases [1, 6]. We focus on the phosphatidylinositol 3 kinase (PI3Kδ) inhibitor Idelalisib (GS-1101, CAL 101), the clinical rationale behind its use in the treatment of CLL, and the outcomes of various preclinical and clinical trials studying the use of Idelalisib alone or in combination with other therapeutic agents for treatment of both initial and relapse/refractory cases of CLL
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