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New Data Show GlivecŪ Halts Progression to Advanced Stages of Life-Threatening Form of Leukemia in Sixth Year of Treatment

BASEL, SWITZERLAND -- December 10, 2007 -- New data from the largest clinical trial in newly diagnosed patients with a life-threatening form of leukemia showed that long-term use of GlivecŪ (imatinib)[*] can halt progression to advanced disease stages in the sixth year of treatment.

Results of the International Randomized Interferon versus STI571 (IRIS) study reveal that after two years of treatment, the rate of disease progression continued to decline and fell to 0% in the study's sixth year. In addition, the estimated overall six-year survival rate for patients treated with Glivec was 88%.

Lead investigators presented the latest findings from this landmark study involving more than 1,100 newly diagnosed patients with a form of the disease known as Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) at the 49th Annual Meeting of the American Society of Hematology (ASH).

Patients in the initial (chronic) phase of CML who received continuous treatment with Glivec did not progress to advanced stages of the disease. Without treatment, CML typically progresses over three to five years from the initial phase through a transition (accelerated) phase to a rapidly fatal form called blast crisis[1].

"If this survival trend continues, many patients with CML may approach normal life expectancy with continued Glivec treatment," said Dr. Brian Druker, MD, Director of the Oregon Health & Science University Cancer Institute Center; the JELD-WEN Chair of Leukemia Research, Howard Hughes Medical Institute Investigator and a member of the National Academy of Sciences.

Most CML patients are in the chronic phase when the disease is diagnosed. Before Glivec was available, about 50% of patients with Ph+ CML progressed from the initial phase to more advanced stages after only three to five years[2]. Once patients reached the final blast crisis phase, survival was generally three to six months[3].

With a unique six-year record of safety and efficacy, Glivec remains the first-line drug therapy for all patients with Ph+ CML.

Glivec has continued to be generally well tolerated as initial drug therapy for Ph+ CML in chronic phase. At the six-year follow-up, the type and frequency of adverse events were similar to previously reported profiles. Newly occurring or worsening grade 3 or 4 hematologic or biochemical adverse events were infrequent.

IRIS is an open-label Phase III clinical trial enrolling 1,106 newly diagnosed patients with Ph+ CML in chronic phase in 177 centers across 16 countries. There are two arms to the study: one group of patients received Glivec 400 mg per day, while the other received a target dose of interferon (IFN) of 5 MIU/m2/day in combination with cytarabine (Ara-C) 20 mg/m2/day for 10 days each month. Because of tolerability issues, lack of response or loss of response, 65% of patients in the IFN/Ara-C arm crossed over to the Glivec arm, whereas only 3% of patients in the Glivec arm crossed over to the IFN/Ara-C arm[1].

Cumulative best responses to Glivec treatment improved dramatically between the first and sixth years of treatment. Over the period, the number of Glivec-treated patients showing complete cytogenetic response (or elimination of the abnormal Philadelphia chromosome associated with CML) rose from 70% in the first year to 87% by the sixth year of treatment.

The estimated overall survival rate for patients receiving Glivec was 88% when considering deaths from all causes. When deaths from causes unrelated to CML or following transplantation are excluded, the estimated overall survival rate was 95%[1]. Less than 5% of patients died of CML[1].

The rate of disease progression continued to decline in the sixth year of the study, with a 0.4% event rate (including loss of response) and a 0% rate of progression to advanced disease between years five and six among patients who remained on Glivec after five years.

No new serious safety issues were identified between the fifth and sixth year of treatment[1].

In a separate study published last month in the ASH journal Blood, Glivec produced a high six-year estimated overall survival rate (76%) in chronic-phase CML patients who had previously failed treatment with interferon. Most of these high-risk patients (57%) also achieved the best treatment outcome - a complete cytogenetic response - and many (40%) were still in cytogenetic response after six years of treatment with Glivec[4].

REFERENCES:
1. Hochhaus, A. IRIS 6-Year Follow-Up: Sustained Survival and Declining Annual Rate of Transformation in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Imatinib. Oral Presentation. American Society of Hematology Annual Meeting, 2007. Abstract #25.
2. Faderl S; Talpaz M; Estrov Z; O'Brien S; Kurzrock R; Kantarjian HM. The biology of chronic myeloid leukemia. N Engl J Med. 341:164-72, 1999.
3. Besa, Emmanuel C. Chronic Myelogenous Leukemia. E-Medicine, WebMD. Available at:
http://www.emedicine.com/med/topic371.htm. Accessed 30 November, 2007.
4. Hochhaus, A., Druker, B. et al. Favorable long-term follow-up results over six years for response, survival and safety with imatinib mesylate therapy in chronic phase chronic myeloid leukemia post failure of interferon alpha treatment. Blood, 2007.

[*] Known as GleevecŪ (imatinib mesylate) tablets in the US, Canada and Israel.


SOURCE: Novartis

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