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Content Update

December 12, 2017

Long-Term Outcomes of Imatinib (Gleevec®) Treatment for Chronic Myeloid Leukemia: A follow-up study reported the long-term outcomes of the phase 3 International Randomized Study of Interferon and STI571 (IRIS) trial, which showed that imatinib was more effective and better tolerated than interferon alfa plus low-dose cytarabine in patients with newly-diagnosed chronic myeloid leukemia (CML) in the chronic phase. The follow-up study evaluated patients who had been randomized to receive imatinib; overall survival at 10 years was 83.3% with a median follow-up of 10.9 years. The discontinuation rate of imatinib due to adverse events (6.9%) was much lower than the interferon alfa plus cytarabine study arm (26.2%). These results show that the efficacy of imatinib 400 mg daily is maintained with a tolerable safety profile; imatinib and the second-generation tyrosine kinase inhibitors dasatinib and nilotinib are recommended as first-line therapy for patients with CML in chronic phase.

Content Update

April 10, 2017

Venetoclax for relapsed or refractory chronic lymphocytic leukemia: Venetoclax (Venclexta®) is an oral B-cell lymphoma-2 (BCL-2) inhibitor approved for treatment of chronic lymphocytic leukemia (CLL) with 17p deletion in patients who have received at least one prior therapy. A multicenter, open-label, phase II study of 107 patients demonstrated a high and durable overall response rate in patients with relapsed or refractory CLL with del(17p). Venetoclax is the first FDA-approved treatment that targets the B-cell lymphoma 2 (BCL-2) protein, which supports cancer cell growth and is overexpressed in many patients with CLL.

KEY CONCEPTS

KEY CONCEPTS

  • Image not available. Chronic myelogenous leukemia (CML) is defined by the presence of the Philadelphia chromosome (Ph), a translocation between chromosomes 9 and 22. The resulting abnormal fusion protein, p210 BCR-ABL, phosphorylates tyrosine kinase residues and is constitutively active, resulting in uncontrolled hematopoietic cell proliferation.

  • Image not available. Without treatment, the disease course of CML is characterized by a progressive increase in white blood cells over a period of years that ultimately transforms to an acute leukemia.

  • Image not available. The commercially available tyrosine kinase inhibitors, imatinib, dasatinib, nilotinib, bosutinib, and ponatinib have demonstrated efficacy in treatment of newly diagnosed CML patients and in patients with either accelerated phase or blast crisis.

  • Image not available. CML monitoring requires assessment of milestones throughout the therapy such as hematologic, cytogenetic, and molecular responses, the ideal of which is a molecular response.

  • Image not available. Allogeneic hematopoietic stem cell transplant (HSCT) is the only known curative treatment option for CML and is reserved for patients with a suitable donor and progression after treatment with tyrosine kinase-based therapy.

  • Image not available. The management of chronic lymphocytic leukemia (CLL) is highly individualized and includes observation in patients with early-stage disease and treatment with targeted therapy, chemotherapy, biologic therapy, or both in patients with more advanced disease.

  • Image not available. Alemtuzumab, ofatumumab, obinutuzumab, and rituximab are monoclonal antibodies that are indicated for the treatment of CLL.

  • Image not available. Regimens such as fludarabine, cyclophosphamide, and rituximab are considered as first-line therapy for patients with CLL who are younger or have more ...

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