U.S. Residents
Frequently Asked Questions
General Glivec® FAQ
1.1 Are there any long-term survival data with Glivec (imatinib)?
1.2 Has resistance to Glivec been observed?
1.3 Does Glivec work in other cancers?
Diagnosis and Treatment With Glivec
2.1 When is the optimal point in the treatment of CML patients to use Glivec therapy, especially in relation to SCT?
2.2 Is there evidence to substantiate the use of Glivec as first-line treatment in CML?
2.3 Are there data comparing Glivec with IFN-α?
CML Response to Glivec
3.1 How quickly will a patient respond to Glivec?
3.2 Are there any data demonstrating that the response to Glivec will be durable?
Answers
General
1.1 Are there any long-term survival data with Glivec?
- Few drugs have succeeded to the extent that Glivec has in fundamentally changing the natural history of a disease.
- The 5-year follow-up data from the large phase 3 randomised IRIS trial confirm that Glivec is the standard first-line therapy for all CML patients4-6.
- An 89% overall survival rate at 5 years with Glivec exceeds that of all other CML therapies, with <5% of deaths related to CML.
- An estimated 98% of patients in chronic-phase CML have had a best response of CHR, and an estimated 92% of patients have had a best response of major cytogenetic response with Glivec.
- Late responses to Glivec occur and responses are durable.
- Annual risk of progression is decreasing with time.
- The annual rate of progression to advanced phases of CML (accelerated phase/blast crisis) at year 5 declined to 0.6% (from 1.5% in year 1).
- Increasing the daily dose of Glivec to 600 or 800 mg may be considered for patients in the absence of severe adverse drug reaction and severe non-leukaemia-related neutropenia or thrombocytopenia in certain circumstances, including disease progression, failure to achieve response within prespecified timepoints, or loss of response (refer to SmPC for further details)4.
- For children, dose increases from 340 mg/m2 daily to 570 mg/m2 daily (not to exceed the total daily dose of 800 mg) may be considered in the absence of severe adverse drug reaction and the absence of severe non-leukaemia-related neutropaenia or thrombocytopaenia in certain circumstances, including disease progression, failure to achieve response within prespecified time points, or loss of response (refer to SmPC for further details)4.
- Overall risk of progression to advanced phase is low and is associated with the degree of response, regardless of when achieved.
- As experience accumulates with Glivec in CML, it is apparent that some patients in chronic phase and a substantial proportion of patients in the advanced disease phases are either initially refractory to Glivec therapy (primary or intrinsic resistance) or develop resistance with time (secondary resistance or relapse) after an initial response.
- The most important approach to avoiding resistance is to administer full therapeutic doses of Glivec as early as possible49. Starting with at least the approved Glivec dosage, 400 mg/d for chronic-phase and 600 mg/d for advanced-phase CML, can aid in diminishing relapse risk50. Dose escalation has been investigated as a means of avoiding resistance49, 79.
- Glivec has been approved for the treatment of4:
- Adult and paediatric patients with newly diagnosed Ph+ CML for whom bone marrow transplantation is not considered as the first line of treatment
- Adult and paediatric patients with Ph+ CML in chronic phase after failure of interferon-alfa therapy, or in accelerated phase or blast crisis
- Adult patients with newly diagnosed Ph+ ALL integrated with chemotherapy
- Adult patients with relapsed or refractory Ph+ ALL as monotherapy
- Adult patients with myelodysplastic syndrome/myeloproliferative diseases (MDS/MPD) associated with platelet-derived growth factor receptor (PDGFR) gene rearrangements
- Adult patients with advanced hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukaemia (CEL) with FIP1L1-PDGFRα rearrangement
- Glivec is also indicated for the treatment of:
- Adult patients with KIT (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumours (GIST)
- Adult patients with unresectable dermatofibrosarcoma protuberans (DFSP) and adult patients with recurrent and/or metastatic DFSP who are not eligible for surgery
- An active Glivec clinical study program is continuing for CML, as well as for new indications in a variety of haematological malignancies and solid tumours. Clinicians wishing to obtain information about these trials can consult the international trial registries and Novartis Oncology.
Please refer to local prescribing information for specific indications.
Diagnosis and Treatment With Glivec
2.1 When is the optimal point in the treatment of CML patients to use Glivec therapy, especially in relation to SCT?
- An expert panel recommends using Glivec as the preferred initial treatment of patients with CML, reserving SCT for those patients in whom this therapy is appropriate8.
- Glivec continues to be recommended as first-line treatment for CML, based on evidence reviewed by an international expert panel8.
- Yes. The large phase 3 randomised IRIS trial has demonstrated superior efficacy of Glivec over IFN-α + Ara-C, the previous standard of care for patients with newly diagnosed chronic-phase CML. Large phase 2 studies have demonstrated efficacy of Glivec in more advanced phases of CML4.
- The large phase 3 randomised IRIS trial provides data to support that Glivec therapy for chronic-phase CML patients has superior efficacy compared with IFN-α + Ara-C, the previous standard of care in newly diagnosed chronic phase patients with CML81. Glivec is well tolerated, with most adverse events being mild to moderate in severity.
- Glivec has also demonstrated efficacy in patients who are refractory or intolerant to IFN-α4.
- Data from a historical comparison between 2 phase 3 trials demonstrate that there is a significant survival advantage (P < 0.001) when patients with chronic-phase CML were treated with Glivec (in the IRIS trial) compared with patients treated with IFN-α + Ara-C (in the CML91 trial)80.
CML Response to Glivec
3.1 How quickly will a patient respond to Glivec?
- Most patients respond to Glivec very quickly.
- Overall risk of progression to advanced phase is low and is associated with the degree of response, regardless of when achieved.
- Achievement of CCyR at 24 months resulted in similar levels of protection from progression to accelerated phase or blast crisis phases at 60 months as a CCyR achieved at 12 or 18 months.
- Patients who achieved either CCyR or PCyR within the first 24 months of imatinib therapy have a high rate of survival without progression to accelerated phase or blast crisis phases compared with patients without a cytogenetic response at 60 months
- Criteria to determine optimal management of CML with Glivec therapy based on specified time points in which responses are achieved have been proposed by an expert panel8.
- The 5-year follow-up data from the large phase 3 randomised IRIS trial demonstrate that late responses to Glivec occur and responses are durable.
- Estimated 5-year survival rates of 89% have been reported for newly diagnosed chronic-phase CML patients receiving 400 mg/d of Glivec in the IRIS trial5,6.
- An estimated 98% of patients in chronic-phase CML have had a best response of CHR, and an estimated 92% of patients have had a best response of major cytogenetic response with Glivec.
- Six-year follow-up of patients in the phase 2 Study 110 indicates that Glivec substantially improves the survival of chronic-phase CML in patients who previously failed IFN therapy. This report also confirms the beneficial effects of cytogenetic responses on long-term outcomes with Glivec81.