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FDA Approves Idelalisib (Zydelig) for relapsed-CLL

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    July 24, 2014 9:00:07 AM PDT

    Idelalisib

    On July 23, 2014, the U.S. Food and Drug Administration (FDA) approved idelalisib (Zydelig tablets, GileadSciences, Inc.) for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, for whom rituximab alone would be considered appropriate therapy due to other co-morbidities. 

    FDA also granted accelerated approval to idelalisib for the treatment of patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) or relapsed small lymphocytic lymphoma (SLL) who have received at least two prior systemic therapies.
    FDA Indications(sometimes, often the medical boards ignore this part)

    Zydelig is a kinase inhibitor indicated for the treatment of patients with:
    Relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities. 

    Relapsed follicular B-cell non-Hodgkin lymphoma (FL) in patients
    who have received at least two prior systemic therapies. (1.2)
    Relapsed small lymphocytic lymphoma (SLL) in patients who have
    received at least two prior systemic therapies. (1.3)

    The approval for CLL was based on the results of an international, multi-center, randomized (1:1), placebo-controlled trial of 220 patients comparing idelalisib 150 mg twice daily in combination with rituximab to placebo in combination with rituximab. Rituximab was administered in 8 doses (first dose at 375 mg/m2, subsequent doses at 500 mg/m2) every 2 weeks for 4 infusions, then every 4 weeks for 4 infusions.
    Progression-free survival (PFS) assessed by blinded independent review committee (IRC) was the primary efficacy endpoint. The trial was stopped early based on an interim analysis; median duration of exposure to idelalisib was 5.0 months. Median PFS was not reached (95% CI 10.7, NR) in the idelalisib plus rituximab arm and was 5.5 months (95% CI 3.8, 7.1) in the placebo plus rituximab arm [HR 0.18 (95% CI: 0.10, 0.32); p < 0.0001]. 
    Accelerated approval for FL and SLL was based on the results of a multi-center, single arm, open-label trial enrolling 123 patients with relapsed indolent non-Hodgkin lymphomas who were started on idelalisib 150 mg twice daily. The primary efficacy endpoint was overall response rate (ORR) as assessed by an IRC. In patients with FL, the ORR was 54% (95% CI: 42, 66), and the median response duration was not evaluable. In patients with SLL, the ORR was 58% (95% CI: 37, 77), and the median response duration was 11.9 months.
    Idelalisib is being approved with a Boxed Warning alerting patients and healthcare professionals of the following fatal and serious adverse reactions: hepatotoxicity, severe diarrhea or colitis, pneumonitis, and intestinal perforation. The most common adverse reactions (incidence greater than or equal to 20%) are diarrhea, pyrexia, fatigue, nausea, cough, pneumonia, abdominal pain, chills, and rash. The most common lab abnormalities (incidence greater than or equal to 30%) are neutropenia, hypertriglyceridemia, hyperglycemia, ALT elevations, and AST elevations.
    The recommended dose and schedule for idelalisib is 150 mg orally twice daily for patients with FL and SLL and in combination with rituximab for patients with CLL. 
    Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at: 
     
    http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm406410.htm
    Abstract

    Two patients with classic chronic lymphocytic leukemia had meningeal leukemia as a complication of their disease. Intrathecal chemotherapy was successful in eradicating signs and symptoms of meningeal involvement. One of these patients is alive without evidence of central nervous system leukemia 30 months after diagnosis of meningeal leukemia, and 5½ years after the diagnosis of chronic lymphocytic leukemia. Although uncommon, meningeal involvement in chronic lymphocytic leukemia may occur at various times in the course of the disease, it responds to conventional therapy.

    Cerebrospinal fluid from a patient 

    56-year-old male with chronic lymphocytic leukemia that was diagnosed shortly after he presented in 1974 with increased lymphocytes in his blood (lymphocytosis), enlargement of the spleen (blood tumor there too) [splenomegaly]) A bone marrow biopsy showed 80% lymphocytes.
    The patient received chemotherapy with cyclophosphamide, vincristine, and the anti-inflammatory medicaiton prednisone, This treatment resulted in remission (went away) of the tumor burden (killed most of these tumor cells), but it did not kill them all. you can only give so much chemotherapy because it kills the healthy cells and the tumor cells.

    Leukocyte count 253/mm(3) with 100% mature lymphocytes. The patient underwent cranial radiation, and received two doses of intrathecal (within the meninges)0 methotrexate with clearing of his symptoms. Progressive inanition (wasting) developed, and he died with congestive heart failure. four months after the meningeal leukemia (arachnoid membranes are one of the layers of the meninges), in 1976 . He did not have meningeal leukemia again prior to death (it was elsewhere though, a bone marrow is used in many patients with lymphoma, a key part of the workup, in contrast to what the medical board might assert).


    This post was edited by DrSocial Admin at April 5, 2015 11:45:27 AM PDT
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